Characterization of alternative plasticizers in poly(vinyl chloride) sheets for blood containers

This study aimed to optimize the ratio of dioctyl 4‐cyclohexene‐1,2‐dicarboxylate (DOTH) and di‐isononyl‐cyclohexane‐1,2‐dicarboxylate (DINCH^®) for use as plasticizers in poly(vinyl chloride) (PVC) sheets. We also evaluated the biological safety of DOTH for its potential to be part of a safe PVC‐based blood container. The suppression of hemolysis in mannitol‐adenine‐phosphate / red cell concentrates (MAP/RCC) with DOTH/(DINCH^®‐PVC) sheets and the elution of plasticizers from the sheets increased with higher DOTH compositions. The properties of the PVC sheet containing DOTH and DINCH^® in the ratio of 25:33 parts against PVC 100 parts as a weight were almost identical to the PVC sheet made of di(2‐ethylhexyl) phthalate. From a subchronic toxicity test, DOTH did not show any adverse effects on all organs, including the testes, epididymis, liver, and kidneys. The no‐observed‐adverse‐effect level was 300 mg/kg body weight/day in a rat. These results suggest that DOTH/DINCH^® (25:33) is a promising candidate for the replacement of di(2‐ethylhexyl) phthalate in blood containers. J. VINYL ADDIT. TECHNOL., 22:520–528, 2016. © 2015 Society of Plastics Engineers     

Effects of passive smoking on the regulation of rat aortic cholesteryl ester hydrolases by signal transduction

The effects of exogenous oxidative stress due to passive smoking on cholesteryl ester (CE)-metabolizing enzymes and their regulatory kinases were examined by exposing rats to cigarette smoke (CS) for a 1-h period twice a day for 8, 12, or 20 wk. An oxidatively modified low density lipoprotein (Ox-LDL) with a high lipid peroxide was identified in three CS groups after all three exposure periods. The rat aortic acid and neutral CE hydrolases (ACEH and NCEH) were activated to similar extents by both cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) in the presence of their respective cofactors. The aortic PKC activity in the three CS groups exhibited significant reductions of 72, 84, and 75% as compared with the respective controls, which coincided with the reductions in the ACEH activities (86, 71, and 80%, respectively), whereas the PKA activities increased to 121, 197, and 252% in the three CS groups, respectively. Reflecting the increase of the PKA activity, the NCEH activity exhibited increases of 112% at 8 wk and 140% until 12 wk of exposure and decreased by 50% of the control value at 20 wk of exposure, suggesting inactivation of NCEH itself. The activation of acyl-CoA:cholesterol O-acyl-transferase activity was associated with an increase of free cholesterol in aorta. The vitamin E diet prevented the formation of Ox-LDL and the oxidative inactivation of most enzymes, especially PKC, until 12 wk, but was less effective by 20 wk. The oxidative inactivation of PKC, particularly its activated form that translocated to the membrane fraction, was confirmed in the in vitro exposure to active oxygen generators at an optimal concentration; this inactivation was prevented by catalase and superoxide dismutase. These results suggested that the formation of Ox-LDL and alterations in CE-metabolizing enzymes caused by passive smoking could contribute to a twofold increase in the aortic CE content, thereby contributing to one of the mechanisms for atherosclerosis associated with smoking.     

Nonlinear Interfacial Friction of 4He Films Absorbed on Grafoil

No Heading We measured the slippage of ⁴He films adsorbed on Grafoil using the quartz-crystal microbalance (QCM) technique. The slippage of ⁴He films depended on the oscillating amplitude. In a large oscillating amplitude of a 5.0 MHz quartz crystal, ⁴He films underwent slipping gradually below a certain temperature. On the other hand, in a small oscillating amplitude, another additional increase appeared.PACS numbers: 67.20. +k, 81.40.Pq     

Synergistic Effects of Venetoclax and Daratumumab on Antibody-Dependent Cell-Mediated Natural Killer Cytotoxicity in Multiple Myeloma

The prognosis of multiple myeloma (MM) has drastically improved owing to the development of new drugs, such as proteasome inhibitors and immunomodulatory drugs. Nevertheless, MM is an extremely challenging disease, and many patients are still refractory to the existing therapies, thus requiring new treatment alternatives. Venetoclax is a selective, orally bioavailable inhibitor of BCL-2 that shows efficacy in MM not only as a single agent but also in combination therapy, especially for MM patients with translocation t(11;14). However, many patients are refractory to this drug. Here, we treated the MM cell lines KMS12PE and KMS27 with a combination treatment of venetoclax targeting BCL-2 and daratumumab targeting CD38 to evaluate the synergistic cytotoxicity of these drugs in vitro. MM cell lines were co-cultured with natural killer (NK) cells at an effector:target ratio of 0.3:1 in the presence of serial concentrations of daratumumab and venetoclax, and the resulting apoptotic MM cells were detected by flow cytometry using annexin V. These results indicated that the antibody-dependent cell-mediated NK cytotoxicity was enhanced in KMS12PE and KMS27 cells harboring t(11;14) with a high BCL-2 expression, suggesting that the combination treatment of venetoclax and daratumumab should be especially effective in patients with these characteristics.     

A method for estimating visceral fat from the elasticity of lumbar subcutaneous fat

Since metabolic syndrome is a cause of lifestyle-related diseases, and its early diagnosis and an evaluation of visceral fat are important, this study proposes a new method of estimating the amount of fat. The goal of this study is to estimate visceral fat from estimation of subcutaneous fat and total fat. The subcutaneous fat is estimated from the elasticity of the lumbar area, and the total fat is estimated from body information such as the abdominal vertical and lateral width, and body weight. Finally, the estimated subcutaneous fat is subtracted from the estimated total fat to calculate the visceral fat. Measurement tests conducted to verify the constructed visceral fat estimation model showed good results, with a correlation of 0.96 between the visceral fat area estimated by the proposed method and the actual measured area. The reproducibility of the estimation model was also verified by the cross validation method.     

Accurate determination of multiple sets of single molecular conductance of Au/1,6-hexanedithiol/Au break junctions by ultra-high vacuum-scanning tunneling microscope and analyses of individual current-separation curves

The effect of the binding sites of the terminal groups -S on gold on currents through a single molecular junction (MJ) of Au/1,6-hexanedithiol/Au was studied by measuring current-separation (i-s) curves during repeated formation of a break junction in UHV-STM. Three different single molecular conductance (SMC) values (i.e. G(m)(HC), G(m)(MC) and G(m)(LC)) were found by a careful analysis of corrected current histograms for background tunneling currents using a previously developed robust statistical analysis. Here, HC, MC and LC represent a single MJ with high, medium and low conductance, respectively. These three SMC values are attributed to three different contact modes (i.e. strong-strong, strong-weak (or weak-strong) and weak-weak bindings at the two ends). In addition to these three SMC values due to the different contacts, another lower SMC value was newly observed in the corrected histogram. The presence of the fourth SMC is specific to MJs of alkanedithiols and is attributable to LC of a single alkylene chain with gauche rich conformation, which has a lower SMC value than that of LC with all-trans conformation as proposed previously (Fujihira M et al 2006 Phys. Chem. Chem. Phys. 8 3876). Due to the effects of the contact and the conformational change, it was difficult to determine six different SMC values corresponding to two different conformations (i.e. gauche-rich versus all-trans) with three different contacts (i.e. HC, MC and LC). In addition to this complexity, the current steps corresponding to HC, MC and LC almost always appeared in this order in measured i-s curves during separation. The current step observed here could not only be a contribution from a single molecule, but also contributions from a few groups of molecules that happen to link gold atoms of the substrate with those of the tip apex. Therefore, the SMC value for HC obtained as a peak or a set of peaks in the current histogram could be based upon the sum of the current of HC and those of MCs and LCs coexisting in parallel, unless every MJ would change successively from HC to MC and MC to LC. Namely, the currents through coexisting MCs and LCs would raise the intrinsic current observed for HC itself, while those through coexisting LCs would raise the intrinsic current for MC. To avoid such errors in determining the true SMC, we demonstrate here a new method based upon analyses of individual i-s curves referred to as jump height analyses of individual i-s curves. By this method, the true SMC of LC(all-trans) was determined to be 1.6?nS (i.e. G(m) (LC, all-trans) of 2.1 × 10(-5)G(o)) without ambiguity in spite of the possible presence of LCs(gauche rich) in parallel.     

Light-activated oxidize-mimicking nanozyme for inhibition of pathogenic Escherichia coli

Here we demonstrate the nanozyme properties of histidine-containing carbon nanodots as externally tunable antibacterial agents through irradiation with visible (VIS) light. The correlative (light and electron) microscopic analysis of treated Escherichia coli O157:H7 revealed that the positive charged carbon nanoparticles might readily adsorb at slightly acid pH on the negative charged cellular envelope of bacteria, and thus, inhibit their growth with over 80% efficiency under illumination with VIS light. The reason was that under VIS irradiation in the range 400–500 nm the adsorbed nanoparticles behaved as effective oxidase-mimicking enzymes and generated reactive oxygen species on the labeled cells. Thus, the light-activated artificial nanozyme caused serious physical damaging of bacterial envelope, which was leading to irreversible cellular inhibition. The outcomes of this study are likely to broaden the scope of designed photoactive carbon nanozymes as powerful antibacterial agents against the emergence of antibiotic and multidrug-resistant strains, as well as proposing of new strategies for infection control.