Cell-Permeable Succinate Rescues Mitochondrial Respiration in Cellular Models of Statin Toxicity

Statins are the cornerstone of lipid-lowering therapy. Although generally well tolerated, statin-associated muscle symptoms (SAMS) represent the main reason for treatment discontinuation. Mitochondrial dysfunction of complex I has been implicated in the pathophysiology of SAMS. The present study proposed to assess the concentration-dependent ex vivo effects of three statins on mitochondrial respiration in viable human platelets and to investigate whether a cell-permeable prodrug of succinate (complex II substrate) can compensate for statin-induced mitochondrial dysfunction. Mitochondrial respiration was assessed by high-resolution respirometry in human platelets, acutely exposed to statins in the presence/absence of the prodrug NV118. Statins concentration-dependently inhibited mitochondrial respiration in both intact and permeabilized cells. Further, statins caused an increase in non-ATP generating oxygen consumption (uncoupling), severely limiting the OXPHOS coupling efficiency, a measure of the ATP generating capacity. Cerivastatin (commercially withdrawn due to muscle toxicity) displayed a similar inhibitory capacity compared with the widely prescribed and tolerable atorvastatin, but did not elicit direct complex I inhibition. NV118 increased succinate-supported mitochondrial oxygen consumption in atorvastatin/cerivastatin-exposed platelets leading to normalization of coupled (ATP generating) respiration. The results acquired in isolated human platelets were validated in a limited set of experiments using atorvastatin in HepG2 cells, reinforcing the generalizability of the findings.     

Effects of feed composition,protein denaturation and storage of milk serum protein/lactose powders on lactosylation

During whey powder production, the feed is subjected to several heat treatments which can cause lactosylation of proteins. In this study, lactosylation of whey proteins was evaluated in spray-dried powders before and after storage by varying the native protein fraction as well as the serum protein/lactose ratio in the powders. The lactosylation of native α-lactalbumin and β-lactoglobulin in the powders before storage was not affected to a large extent by the protein denaturation or if the feed had been heat treated in a high or low lactose environment. After storage (relative humidity of 23.5%, 30 °C, 25 days), the kinetic of lactosylation tended to increase with increasing native protein fraction and bulk protein content in the powders. An explanation could be that proteins dissolved in the lactose glassy structure might have a lower reactivity, while proteins present in the protein glassy structure with dissolved lactose may display higher lactosylation reactivity.     

Influence of processing on stability,microstructure and thermoelectric properties of Ca3Co4 − xO9 + δ

Due to high figure of merit, Ca₃Co_4 ? xO_9 + δ (CCO) has potential as p-type material for high-temperature thermoelectrics. Here, the influence of processing including solid state sintering, spark plasma sintering and post-calcination on stability, microstructure and thermoelectric properties is reported. By a new post-calcination approach, single-phase materials were obtained from precursors to final dense ceramics in one step. The highest zT of 0.11 was recorded at 800 °C for CCO with 98 and 72% relative densities. In situ high-temperature X-ray diffraction in air and oxygen revealed a higher stability of CCO in oxygen (～970 °C) than in air (～930 °C), with formation of Ca₃Co₂O₆ which also showed high stability in oxygen, even at 1125 °C. Since achievement of phase pure high density CCO by post-calcination method in air is challenging, the phase stability of CCO in oxygen is important for understanding and further improvement of the method.     

Human Anti-Oxidation Protein A1M—A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy

Peptide receptor radionuclide therapy (PRRT) has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α₁-microglobulin (A1M) is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies.     

Reduced autonomy workspace (RAW)—an interaction design approach for human-automation cooperation

Cognition, Technology & Work - Lack of support for handling a reduction of autonomy in a highly autonomous automation may lead to a stressful situation for a human when forced to take over. We...     

Acid Hydrogen Peroxide Treatment of Norway Spruce TMP: The Effect of an Extended pH Range when Catalyzed by Free Ferrous and Free or EDG/EDTA-Chelated Ferric Ions

The influence of different types of iron salts (i.e., ferrous or ferric cations with sulphate, nitrate or chloride anions) on the reaction between coarse thermomechanical pulp and acid hydrogen peroxide (Fenton chemistry) was studied when the initial pH was 3.2 and 5.3. Also, ferric ions chelated with EDTA or EDG at different molar ratios were compared with ferrous sulphate when the initial pH was extended from about 3 to 8. Different anions of ferric ion salt gave a similar catalytic effect. At an initial pH of 7–8, the ferric-EDTA catalyzed reaction resulted in similar or higher hydrogen peroxide consumption and more detectable hydroxyl radicals than the ferrous sulphate catalyzed reaction, but less reaction with the pulp was indicated. Between pH 5–8, using Fe-EDG as a catalyst gave higher hydrogen peroxide consumption and more detectable hydroxyl radicals than if using ferrous sulphate; however, the measured effect on the pulp was similar or less.     

Kinetic modeling of Fe‐BEA as NH3‐SCR catalyst—effect of phosphorous

The focus of this work is to investigate whether a previously developed microkinetic deactivation model for hydrothermally treated Fe‐BEA as NH₃‐SCR catalyst can be applied to describe chemical deactivation of Fe‐BEA due to phosphorous exposure. The model describes the experiments well for Fe‐BEA before and after phosphorous exposure by decreasing the site density, representing deactivation of sites due to formation of metaphosphates blocking the active iron sites, while the kinetic parameters are kept constant. Furthermore, the results show that the activity for low‐temperature selective catalytic reduction (SCR) is very sensitive to loss of active monomeric iron species due to phosphorous poisoning compared to high‐temperature SCR. Finally, the ammonia inhibition simulations show that exposure to phosphorous may affect the internal transport of ammonia between ammonia storage sites buffering the active iron sites, which results in a lower SCR performance during transient conditions. © 2014 American Institute of Chemical Engineers AIChE J, 61: 215–223, 2015     

Associations between driving under the influence of alcohol or drugs,speeding and seatbelt use among fatally injured car drivers in Norway

Since 2005, all fatal road traffic crashes in Norway have been analyzed in-depth by multidisciplinary investigation teams organized by the Norwegian Public Roads Administration (NPRA). During the period 2005–2010, 608 drivers of cars or vans were killed in road traffic crashes. Blood samples were collected from 372 (61%) of the drivers and analyzed for alcohol and a large number of psychoactive drugs at the Norwegian Institute of Public Health (NIPH). After coupling the analytical results with the NPRA crash database, 369 drivers with a fatal outcome were identified and included. Alcohol or drug concentrations in blood above the legal limits were found in 39.8% of the drivers who were investigated for alcohol or drug impairment; 33.9% had blood alcohol concentrations above 0.5 g/L or concentrations of drugs above the equivalent Norwegian legal impairment limits or concentrations of amphetamines above 200 μg/L. Among drivers with a fatal outcome who had been impaired by alcohol or drugs, 64.6% were unbelted and 71.7% were speeding when the crash occurred; whereas 24.2% and 33.2% of the sober drivers were unbelted or speeding, respectively. Statistically significant associations were found between impairment by alcohol or amphetamines and driving unbelted or speeding. Excessive speeding is one of the main reasons for road traffic crashes and together with being unbelted the main reasons for a fatal outcome. This behavior might in many cases be due to increased risk-taking or negligence of safety measures as a result of alcohol or drug use.