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 Cerivastatin (commercially withdrawn due to muscle toxicity) displayed a similar inhibitory capacity compared with the widely prescribed and tolerable atorvastatin, but did not elicit direct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.     

Surface and interface properties of functionalized polysulfones: Cell‐material interaction and antimicrobial activity

Quaternized polysulfones with different ionic chlorine content tested for biomedical applications were obtained by quaternization reaction of chloromethylated polysulfones with N,N‐dimethylethanolamine. The relationship between the different physical and chemical characteristics of these polymers and their biocompatible and antimicrobial properties was established for maximizing the selectivity and performance of these materials for biomedical applications. Therefore, topographic reorganization of the polysulfonic films induced by the type of nonsolvent in casting solutions of polymer significantly influences films morphology, depending on the charge density of polyelectrolytes, the hydrophilic/hydrophobic characteristics, as well as on the history of the formed films. Furthermore, the study of the adhesion of red blood cells and cohesion of platelets on the surface of quaternized polysulfone films, as well as analysis of antibacterial activity, using Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 25923 microorganisms, contribute to extending the possible applications of quaternized polysulfones as semipermeable membranes in biomedical domains. POLYM. ENG. SCI., 55:2184–2194, 2015. © 2015 Society of Plastics Engineers     

Impact of Some Properties of Quaternized Polysulfone/Poly(Vinylidene Fluoride) Blend on the Potential Biomedical Applications

Blends of quaternized polysulfones with triphenylphosphonium pendant groups/poly(vinylidene fluoride) were analyzed to establish their impact on the rheological, morphological and surface properties, as well as their interactions with some blood compounds. The rheological functions reflect the influence of both polymers’ chemical structures. Blend compositions of the corresponding films influence the surface tension parameters, increase blend hydrophobicity and, implicitly, decrease the polar surface tension parameters. The specific surface characteristics of polymer blends are related to their interactions with some blood constituents and plasma proteins. Also, the specific microarchitecture of the blend represents an excellent scaffold for medical applications.     

Betulinic Acid in Complex with a Gamma-Cyclodextrin Derivative Decreases Proliferation and in Vivo Tumor Development of Non-Metastatic and Metastatic B164A5 Cells

Betulinic acid, a very promising anti-melanoma agent, has very low water solubility that causes low bioavailability. To overcome this inconvenience, a highly water-soluble cyclodextrin was used (octakis-[6-deoxy-6-(2-sulfanyl ethanesulfonic acid)]-γ-cyclodextrin). The complex was physico-chemically analyzed using differential scanning calorimetry (DSC), X-ray and scanning electron microscopy (SEM) methods and then in vitro tested for its antiproliferative activity by the MTT assay and by cell cycle analysis. Finally, the complex was tested in vivo using an animal model of murine melanoma developed in C57BL/6J mice, where it caused a reduction in tumor volume and weight. The study revealed the beneficial influence of betulinic acid inclusion into the cyclodextrin in terms of antiproliferative activity and in vivo tumor development.     

Nanofiltration membranes for ionic liquid recovery

Nanofiltration membranes have been developed by interfacial polymerization using base PES ultrafiltration membranes. By varying the concentration of the reactive monomers present as well as the reaction conditions, the structure of the polymerized barrier layer has been modified. Here, the ability to concentrate low molecular weight sugars while allowing dissolved ionic liquids in aqueous solution to be recovered in the permeate has been investigated for application in biomass hydrolysis. The results obtained here indicate that the selectivity for 1-butyl-3-methylimidazoliumchloride (BmimCl) over glucose can be as high as 36.6. The membrane permeance was 2.31 L m^?2 h^?1 bar^?1.     

Polyimides containing 4,4′‐bipyridinium units

New polyimides containing 4,4′‐bipyridinium units were synthesized by the reaction of bis(dichloromaleimide)arylene derivatives with 4,4′‐bipyridine in meta‐cresol. IR and ¹H‐NMR spectroscopy and elemental analysis as well confirmed their structures. The polymers were characterized by viscometric measurements, softening points, and thermogravimetric data. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2091–2100, 2004     

The Classroom of the Future: An Internet‐Delivered National Course on Thermal Management of Electronics

Teaching inter‐disciplinary material poses special challenges due to the diversity of student backgrounds. This problem is compounded if the material being taught is intended for both undergraduate and graduate students. Mechanical Engineering faculty members from three universities have come together to address this problem using a layered, multimedia delivery mechanism via the Internet. This has resulted in the first‐ever, live, full‐duplex, Internet course taught at any of the three partner universities: Auburn University, the University of Maryland, and the University of Minnesota. With the addition of colleagues from industrial sites such as Philips in the Netherlands and three other universities in Japan, Singapore, and Australia, the next offering will expand to become an international course. The authors hope to illustrate that a course delivered over the Internet adds significantly to the learning process in a cost‐effective manner .     

Specific interactions in ternary system quaternized polysulfone/mixed solvent

Theoretical and experimental aspects on the specific interactions developed via electrostatic interactions and hydrogen‐bonding in a ternary system formed of a proton‐donor solvent (N,N‐dimethylformamide or methanol), a proton‐acceptor solvent (water), and a quaternized polysulfone with various contents of ionic chlorine, which indicates a proton‐acceptor character, are investigated. Thus, the interactions of the ternary systems are corrected on the basis of the association phenomena defined through association constants. Numerical values for these constants were evaluated as a function of the system composition, by mathematical simulations for an accurate adjustment of preferential adsorption, determined by the Flory–Huggins–Pouchly theoretical approach applied to the experimental data. POLYM. ENG. SCI., 2009. © 2008 Society of Plastics Engineers     

The characteristics of the viruses involved in avian respiratory diseases and some bird-man epidemiological correlations

The structural gene for translation initiation factor IF2 from Thermus thermophilus was identified on the basis of the N-terminal amino acid sequence of intact T thermophilus IF2 and an internal 25 kDa IF2 fragment. A total of 5135 bp was cloned and sequenced, comprising the open reading frames for p15A, NusA, p10A, IF2, p10B and SecD, which may form an operon. There are pronounced similarities between the operon arrangement and primary sequence of the T thermophilus genes and proteins, respectively, and their counterparts from other organisms. The T thermophilus infB gene was expressed to a high level in E coli. Four hundred milligrams of homogenous T thermophilus IF2 were prepared from 60 g of overproducing cells.