Interleukins 6 and 15 Levels Are Higher in Subcutaneous Adipose Tissue,but Obesity Is Associated with Their Increased Content in Visceral Fat Depots

Excess adiposity is associated with chronic inflammation, which takes part in the development of obesity-related complications. The aim of this study was to establish whether subcutaneous (SAT) or visceral (VAT) adipose tissue plays a major role in synthesis of pro-inflammatory cytokines. Concentrations of interleukins (IL): 1β, 6, 8 and 15 were measured at the protein level by an ELISA-based method and on the mRNA level by real-time PCR in VAT and SAT samples obtained from 49 obese (BMI > 40 kg/m²) and 16 normal-weight (BMI 20–24.9 kg/m²) controls. IL-6 and IL-15 protein concentrations were higher in SAT than in VAT for both obese (p = 0.003 and p < 0.0001, respectively) and control individuals (p = 0.004 and p = 0.001, respectively), while for IL-1β this was observed only in obese subjects (p = 0.047). What characterized obese individuals was the higher expression of IL-6 and IL-15 at the protein level in VAT compared to normal-weight controls (p = 0.047 and p = 0.016, respectively). Additionally, obese individuals with metabolic syndrome had higher IL-1β levels in VAT than did obese individuals without this syndrome (p = 0.003). In conclusion, concentrations of some pro-inflammatory cytokines were higher in SAT than in VAT, but it was the increased pro-inflammatory activity of VAT that was associated with obesity and metabolic syndrome.     

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.     

One‐Step Catalytic Enantioselective α‐Quaternary 5‐Hydroxyproline Synthesis: An Asymmetric Entry to Highly Functionalized α‐Quaternary Proline Derivatives

The highly enantioselective cascade reaction between N‐protected α‐cyanoglycine esters and α,β‐unsaturated aldehydes is disclosed. The reaction represents a one‐step entry to polysubstituted 5‐hydroxyproline derivatives having a quaternary α‐stereocenter generally in high yields with up to >95:5 dr and 99:1 er. It is also a direct catalytic two‐step entry to functionalized α‐quaternary proline derivatives.     

Digital Extraction Column: Measurement and Modeling Techniques

The digitization of extraction columns requires a profound knowledge of the present hydrodynamics/mass transport interaction as well as appropriate measurement techniques for the detection of relevant input and target values. In this article, the different techniques for droplet size distribution as well as concentration determination are presented and new methods for online evaluation are discussed. In combination with the simulation of droplet size, holdup and solute concentration distribution, an online-capable process tool for controlling and optimizing extraction columns will be obtained.     

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Temperature-Dependent Re-alignment of the Short Multifunctional Peptide BP100 in Membranes Revealed by Solid-State NMR Spectroscopy and Molecular Dynamics Simulations

BP100 is a cationic undecamer peptide with antimicrobial and cell-penetrating activities. The orientation of this amphiphilic α-helix in lipid bilayers was examined under numerous conditions using solid-state ¹⁹F, ¹⁵N and ²H NMR. At high temperatures in saturated phosphatidylcholine lipids, BP100 lies flat on the membrane surface, as expected. Upon lowering the temperature towards the lipid phase transition, the helix is found to flip into an upright transmembrane orientation. In thin bilayers, this inserted state was stable at low peptide concentration, but thicker membranes required higher peptide concentrations. In the presence of lysolipids, the inserted state prevailed even at high temperature. Molecular dynamics simulations suggest that BP100 monomer insertion can be stabilized by snorkeling lysine side chains. These results demonstrate that even a very short helix like BP100 can span (and thereby penetrate through) a cellular membrane under suitable conditions.     

Interlaboratory study on lipid oxidation during accelerated storage trials with rapeseed and sunflower oil analyzed by conjugated dienes as primary oxidation products

Accelerated storage tests are frequently used to assess the oxidative stability of foods and related systems due to its reproducibility. Various methods and experimental conditions are used to measure lipid oxidation. Differences between laboratories make it necessary to determine the repeatability and reproducibility of oxidation tests performed under the same conditions. The objective of the present interlaboratory study was to evaluate the outcome of a storage test for two different bulk oils, sunflower oil (SFO) and rapeseed oil (RSO), during a period of 9 weeks at 20°C, 30°C, 40°C, and 60°C. Sixteen laboratories were provided with bottled oils and conducted the storage tests according to a detailed protocol. Lipid oxidation was monitored by the formation of conjugated dienes (CD) and the activation energy (E_a) was determined for comparative purposes and statistically evaluated. An increase in CD formation was observed for both oils when the storage temperature was increased in all laboratories. The E_a,1 ranged from 47.9 to 73.3 kJ mol⁻¹ in RSO and from 27.8 to 62.6 kJ mol⁻¹ in SFO, with average values of 58.2 and 46.8 kJ mol⁻¹, respectively. The reproducibility coefficients were 10.9% and 18.2% for RSO and SFO, respectively. Practical applications: In order to compare results on oxidative stability of foods derived from different studies, the reproducibility of storage tests and methods employed to evaluate the oxidation level should be considered. This study provides fundamental data on the reproducibility of lipid oxidation under accelerated storage conditions and defines important parameters to be considered for the conduction of experiments.     

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     

Aryl Bis‐Sulfonamide Inhibitors of IspF from Arabidopsis thaliana and Plasmodium falciparum

2‐Methylerythritol 2,4‐cyclodiphosphate synthase (IspF) is an essential enzyme for the biosynthesis of isoprenoid precursors in plants and many human pathogens. The protein is an attractive target for the development of anti‐infectives and herbicides. Using a photometric assay, a screen of 40 000 compounds on IspF from Arabidopsis thaliana afforded symmetrical aryl bis‐sulfonamides that inhibit IspF from A. thaliana (AtIspF) and Plasmodium falciparum (PfIspF) with IC₅₀ values in the micromolar range. The ortho‐bis‐sulfonamide structural motif is essential for inhibitory activity. The best derivatives obtained by parallel synthesis showed IC₅₀ values of 1.4 μm against PfIspF and 240 nm against AtIspF. Substantial herbicidal activity was observed at a dose of 2 kg ha^?1. Molecular modeling studies served as the basis for an in silico search targeted at the discovery of novel, non‐symmetrical sulfonamide IspF inhibitors. The designed compounds were found to exhibit inhibitory activities in the double‐digit micromolar IC₅₀ range.