Treatment Strategies that Enhance the Efficacy and Selectivity of Mitochondria-Targeted Anticancer Agents

Nearly a century has passed since Otto Warburg first observed high rates of aerobic glycolysis in a variety of tumor cell types and suggested that this phenomenon might be due to an impaired mitochondrial respiratory capacity in these cells. Subsequently, much has been written about the role of mitochondria in the initiation and/or progression of various forms of cancer, and the possibility of exploiting differences in mitochondrial structure and function between normal and malignant cells as targets for cancer chemotherapy. A number of mitochondria-targeted compounds have shown efficacy in selective cancer cell killing in pre-clinical and early clinical testing, including those that induce mitochondria permeability transition and apoptosis, metabolic inhibitors, and ROS regulators. To date, however, none has exhibited the standards for high selectivity and efficacy and low toxicity necessary to progress beyond phase III clinical trials and be used as a viable, single modality treatment option for human cancers. This review explores alternative treatment strategies that have been shown to enhance the efficacy and selectivity of mitochondria-targeted anticancer agents in vitro and in vivo, and may yet fulfill the clinical promise of exploiting the mitochondrion as a target for cancer chemotherapy.     

Osteogenic Differentiation of Human Adipose-Derived Stem Cells Seeded on a Biomimetic Spongiosa-like Scaffold: Bone Morphogenetic Protein-2 Delivery by Overexpressing Fascia

Human adipose-derived stem cells (hADSCs) have the capacity for osteogenic differentiation and, in combination with suitable biomaterials and growth factors, the regeneration of bone defects. In order to differentiate hADSCs into the osteogenic lineage, bone morphogenetic proteins (BMPs) have been proven to be highly effective, especially when expressed locally by route of gene transfer, providing a constant stimulus over an extended period of time. However, the creation of genetically modified hADSCs is laborious and time-consuming, which hinders clinical translation of the approach. Instead, expedited single-surgery gene therapy strategies must be developed. Therefore, in an in vitro experiment, we evaluated a novel growth factor delivery system, comprising adenoviral BMP-2 transduced fascia tissue in terms of BMP-2 release kinetics and osteogenic effects, on hADSCs seeded on an innovative biomimetic spongiosa-like scaffold. As compared to direct BMP-2 transduction of hADSCs or addition of recombinant BMP-2, overexpressing fascia provided a more uniform, constant level of BMP-2 over 30 days. Despite considerably higher BMP-2 peak levels in the comparison groups, delivery by overexpressing fascia led to a strong osteogenic response of hADSCs. The use of BMP-2 transduced fascia in combination with hADSCs may evolve into an expedited single-surgery gene transfer approach to bone repair.     

Effect of fibrous filter properties on the oil-in-water-emulsion separation and filtration performance

Separation of secondary emulsions of dispersed droplet size less than 10 μm, by means of fibrous medium is a very complex but important process. The study investigates the influence of thin fibrous filter properties, i.e. surface energy, pore size and porosity on the separation performance of an isooctane in water emulsion (0.2%, mean drop size 2 μm). Experiments were carried out on five different filter media with a wide variation in their pore size (2-51 μm), surface energy (14-46 mN/m) and porosity (0.46-0.87) at similar process conditions. Filter media with different wettability are obtained by applying various hydrophobic and hydrophilic coatings. All the used coatings contain nanoparticles (25 nm) to impart nanoscale surface roughness at the single fiber surface. Besides emulsion properties and operating conditions, the phase separation mechanism and performance highly depends on pore size, surface energy and porosity of the filter media. More complete coalescence takes place at reduced pore size and at a surface preferentially wetted by the dispersed phase. Whereas when the pore size equals to the influent droplet size, then the surface wettability of filter is less effective and the separation mechanism is governed by inflow velocity. The emulsion inflow velocity and pressure drop are significantly affected by the filter media air permeability but do not depend on filter surface energy.     

Physik und Technik von Radiofrequenz‐Ionentriebwerken

Physics and Technological Aspects of Radio‐Frequency Ion Thrusters Electric space propulsion devices offer a propellant utilization efficiency orders of magnitude higher than chemical ones. This, among other benefits, motivates the usage of electric propulsion for station keeping, attitude and orbit control, orbit raising and interplanetary deep space missions. In particular, radio‐frequency ion thrusters (RIT) offer even higher efficiency than comparable electric thrusters. This is mainly due to electrostatically generated thrust in RITs which is decoupled from plasma generation which again is ultimately necessary for the production of thrust‐generating requency Ion Thrusters ions. This article gives insight into basic physical processes that occur within the thrusters' discharge vessels which lead to highly efficient, highly resolvable thrust generation. Furthermore, a more general systems engineering observation of the complete thruster system is given with special respect to the radio‐frequency generator (RFG) which is essential to take into account when speaking of overall efficiency. Finally, an overview on alternative propellants to possibly increase cost efficiency of a particular mission is proposed.     

Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial

This study aimed at testing human skin wound healing improvement by a 21-day supplementation of 1.0 g ascorbic acid (AA) and 0.2 g pantothenic acid (PA). 49 patients undergoing surgery for tattoos, by the successive resections procedure, entered a double-blind, prospective and randomized study. Tests performed on both skin and scars determined: hydroxyproline concentrations, number of fibroblasts, trace element contents and mechanical properties. In the 18 supplemented patients, it was shown that in skin (day 8) Fe increased (p < 0.05) and Mn decreased (p < 0.05); in scars (day 21), Cu (p = 0.07) and Mn (p < 0.01) decreased, and Mg (p < 0.05) increased; the mechanical properties of scars in group A were significantly correlated to their contents in Fe, Cu and Zn, whereas no correlation was shown in group B. In blood, AA increased after surgery with supplementation, whereas it decreased in controls. Although no major improvement of the would healing process could be documented in this study, our results suggest that the benefit of AA and PA supplementation could be due to the variations of the trace elements, as they are correlated to mechanical properties of the scars.     

Protein zero (P0)-deficient mice show myelin degeneration in peripheral nerves characteristic of inherited human neuropathies

Mutations in the human gene for the myelin recognition molecule protein zero (P0) give rise to severe and progressive forms of dominantly inherited peripheral neuropathies. We have previously reported that mice homozygous for a null mutation in P0 have severely hypomyelinated nerves ten weeks after birth. Here we show hypomyelination already exists at day four with subsequent demyelination and impaired nerve conduction. Furthermore, heterozygous mutants show normal myelination, but develop progressive demyelination after four months of age. Thus, the pathology of homo- and heterozygous P0 mutants resembles that of the severely affected Déjérine-Sottas and the more mildly affected Charcot-Marie-Tooth type 1B patients, respectively.     

Die Bestimmung des Wasserstoffgehaltes von flüssigem Stahl

Beschreibung der Probenahme von Stählen mit Eisengehalten größer als 95% aus Strangguß- und Blockgußkokillen und einer Apparatur zur Bestimmung des Wasserstoffgehaltes. Entnahme durch geschütztes Tauchen von Quarzgutrohren. Füllen in Tiefen bis zu 250 mm mit ferrostatischem Druck. Umgehung der Probenahme aus oberflächennahen Schichten des Stahlbades zur Vermeidung von Verlusten durch das bisher übliche Einsaugen des flüssigen Stahles in das Quarzgutrohr. – Wasserstoffbestimmung durch Warmauslagerung der Proben im Stickstoffträgergasstrom mit einer Wärmeleitfähigkeitszelle. Elektronische Integration der Meßspannung einer Thermistorbrücke über die Entgasungszeit der Probe.     

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Microstructure, cytotoxicity and corrosion of powder-metallurgical iron alloys for biodegradable bone replacement materials

Up to now biodegradable bone implants with the ability of bearing high loads for the temporary replacement of bones or as osteosynthesis material are not available. Iron and iron based alloys have been identified as appropriate materials, since they combine high strength at medium corrosion rates. Thus, the aim of the present study is the development of a degradable iron based alloy with the perspective of using them as matrix material of cellular structures with biomechanical tailored properties. A powder metallurgical approach has been used to manufacture Fe-C, Fe-0.6P, Fe-1.6P, Fe-B and Fe-Ag samples, which have been tested with respect to their microstructure, their cytotoxicity, and their degradation rate. In order to determine the cytotoxicity of the material a monolayer culture of fibroblast and a perfusion chamber system has been chosen, which was recommended by the ISO 10993-5:1999 for biological testing of medical devices. It has been found, that in particular phosphorus features beneficial properties, since density and thus the strength of the material are increased. No corrosion inhibiting effects of phosphorus on the degradation rate have been found.