Die therapeutische Beeinflußbarkeit von pathologischem Blutfließverhalten bei verschiedenen Hyperlipoproteinämie-Typen

Zusammenfassung Bei Patienten mit primärer Hyperlipoproteinämie konnte die pathologisch erhöhte Serum- und Plasmaviskosität durch Clofibrat (2 × 1 g/die) signifikant gesenkt werden (Ubbelohde-Kapillar-Viskosimeter). Die scheinbare Vollblutviskosität (Wells-Brookfield-Platte-Kegel-Viskosimeter) wurde nur beim Typ IV verbessert. Die relative scheinbare Vollblutviskosität blieb ebenso wie die Erythrozytenflexibilität unbeeinflußt. Zwischen der lipid-(lipoprotein-)senkenden Wirksamkeit und der Viskositätssenkung bestehen gute qualitative Korrelationen. Clofibrat könnte dementsprechend eine Durchblutungsverbesserung herbeiführen. Weiter erscheint es sinnvoll, Antilipidämika auch unter rheologischen Aspekten zu beurteilen.

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Summary In patients with primary hyperlipoproteinemia the pathologically and elevated serum and plasma viscosity could be lowered by a 2 × 1 g/die-clofibrate-therapy (Ubbelohde-capillary-viscosimeter). The apparent blood viscosity (Wells-Brookfield-plate-cone-viscosimeter) was improved only in type IV, whereas the relative apparent whole-blood viscosity and the erythrocyte-flexibility remained unchanged. A good qualitative correlation is found between the lipid-(lipoprotein-) lowering effectiveness and reduction of serum and plasma viscosity. Thus, clofibrate may lead to an improvement in circulation. Furthermore it seems to be reasonable to investigate hypolipidemic agents with respect to blood rheology.

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Vortrag, gehalten auf der Jahrestagung der Deutschen Rheologischen Gesellschaft in Berlin vom 8.–10. Mai 1978.

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Mit 3 Abbildungen und 3 Tabellen     

Protein‐Sized Bright Fluorogenic Nanoparticles Based on Cross‐Linked Calixarene Micelles with Cyanine Corona

The key challenge in the field of fluorescent nanoparticles (NPs) for biological applications is to achieve superior brightness for sizes equivalent to single proteins (3–7 nm). We propose a concept of shell‐cross‐linked fluorescent micelles, in which PEGylated cyanine 3 and 5 bis‐azides form a covalently attached corona on micelles of amphiphilic calixarene bearing four alkyne groups. The fluorescence quantum yield of the obtained monodisperse NPs, with a size of 7 nm, is a function of viscosity and reached up to 15 % in glycerol. In the on‐state they are circa 2‐fold brighter than quantum dots (QD‐585), which makes them the smallest PEGylated organic NPs of this high brightness. FRET between cyanine 3 and 5 cross‐linkers at the surface of NPs suggests their integrity in physiological media, organic solvents, and living cells, in which the NPs rapidly internalize, showing excellent imaging contrast. Calixarene micelles with a cyanine corona constitute a new platform for the development of protein‐sized ultrabright fluorescent NPs.     

Time-dependent nonlinear optical properties of pyroelectric liquid crystalline polymers

Highly oriented pyroelectric liquid-crystalline polymers were prepared by photopolymerization under the influence of a static electric field from binary mixtures of two acrylate monomers exhibiting chiral smectic C mesomorphism. Both monomers contained nitro groups to yield second order nonlinear optical properties (second harmonic generation) and one of the monomers had two functional groups to yield a crosslinked polymer. The room temperature second order nonlinear susceptibility of the polymers showed during the first two hours a 10 % decrease after which it remained constant during the next 48 days. At elevated temperatures there was a significant difference in the nonlinear optical properties over time between crosslinked and uncrosslinked polymers. The uncrosslinked polymer showed a pronounced loss of second order nonlinear optical activity with time at ≥38°C. The crosslinked polymer showed a much smaller and basically a temperature independent decrease rate in the second order nonlinear optical properties at all the ageing temperatures (23-130°C). Both the loss in mesogen order parameter, very evident for the uncrosslinked polymer, and conformational changes occurring within the mesogens (β mechanism), may account for the observations made.     

Layer-by-layer self-assembled polyelectrolyte multilayers with embedded liposomes: immobilized submicronic reactors for mineralization

The development of chemical reactions in nanospaces is of paramount importance for the development of active nanodevices, particularly in nanofluidics. It has been shown in a previous paper that phospholipid vesicles can be incorporated without spontaneous bilayer rupture into poly-L-glutamic acid/poly(allylamine) (PGA/PAH) multilayered polyelectrolyte films. The aim of the present study was to use such a system as an "embedded submicronic reactor" able to trigger precipitation of calcium phosphates within closed spaces through an enzymatic reaction, the enzyme also being encapsulated in the vesicle interior. To this aim, large unilamellar vesicles (LUVs) were produced containing calcium ions as active ions in the mineralization process, spermine as an activator of crystal growth, and alkaline phosphatase as a catalyst to convert phosphate esters into phosphates. After stabilization by adding a layer of poly-(D-lysine), these vesicles were embedded in a (PGA-PAH)n film. A paranitrophenyl phosphate containing solution was then put in contact with this film. It is shown by means of infrared spectroscopy in the attenuated total reflection mode that, consecutively to this contact, calcium phosphates are growing inside the embedded vesicles. By using scanning near-field fluorescence microscopy, it is demonstrated that the alkaline phosphatase enzymes are most probably located inside the vesicles after their embedding. In addition, atomic force microscopy was used to show, after chemical removal of the organic top layer of the film, that the inorganic platelets produced after the precipitation reaction are localized in volumes of similar size and shape as that of the vesicles into which the phosphate ester hydrolysis and subsequent precipitation reaction did occur.     

Transparent,Electrically Conductive Composites Derived from Polypyrrole and Poly[Vinyl Chloride) by Vapor-Phase Polymerization: Effect of Environment on Polymerization and Reaction Mechanism

Abstract

Transparent, electrically conductive composite films were obtained by vapor-phase polymerization of pyrrole into a poly(vinyl chloride) (PVC) matrix containing FeCl₃. The effects of water and of organic solvents on the polymerization were investigated. It was found that the conductance of the films increases in the presence of both water vapor and of good solvents or swelling agents for PVC. The conductivity of the films rises with reaction time and so does the rate of increase with higher FeCl₃ concentration. The production of HCl was monitored by two methods, the precipitation of AgCl in an aqueous solution of silver nitrate and the increase in conductance of an aliquot of distilled water which had been placed into the reaction chamber. On the basis of our experimental results, we propose a reaction mechanism that explains the observed increase of conductance with time. A universal kinetic formula has been derived which relates the increase of electrical conductance to other parameters characterizing the boundary conditions of the polymerization.     

Qualitative and quantitative determination of extractives in heartwood of Scots pine (Pinus sylvestris L.) by gas chromatography

A method for quantitative determination of extractives from heartwood of Scots pine (Pinus sylvestris L.) using gas chromatography (GC) with flame ionization detection (FID) was developed. The limit of detection (LOD) was 0.03 mg/g wood and the linear range (r = 0.9994) was up to 10 mg/g with accuracy within +/- 10% and precision of 18% relative standard deviation. The identification of the extractives was performed using gas chromatography combined with mass spectrometry (GC-MS). The yields of extraction by Soxhlet were tested for solid wood, small particles and fine powder. Small particles were chosen for further analysis. This treatment gave good yields of the most important extractives: pinosylvin, pinosylvin monomethyl ether, resin acids and free fatty acids. The method is used to demonstrate the variation of these extractives across stems and differences in north-south direction.     

Strain sensitive properties of threshold switch devices

A blend of integrated circuit manufacturing techniques and rf sputtering techniques has resulted in TeAs-XXX threshold devices sustaining 100 million switchings. The fabrication and properties of these devices are outlined in this paper. Observations of space charge effects and the influence of strain on the switching properties of these devices are also reported.     

Protein Delivery System Containing a Nickel‐Immobilized Polymer for Multimerization of Affinity‐Purified His‐Tagged Proteins Enhances Cytosolic Transfer

Recombinant proteins with cytosolic or nuclear activities are emerging as tools for interfering with cellular functions. Because such tools rely on vehicles for crossing the plasma membrane we developed a protein delivery system consisting in the assembly of pyridylthiourea‐grafted polyethylenimine (πPEI) with affinity‐purified His‐tagged proteins pre‐organized onto a nickel‐immobilized polymeric guide. The guide was prepared by functionalization of an ornithine polymer with nitrilotriacetic acid groups and shown to bind several His‐tagged proteins. Superstructures were visualized by electron and atomic force microscopy using 2 nm His‐tagged gold nanoparticles as probes. The whole system efficiently carried the green fluorescent protein, single‐chain antibodies or caspase 3, into the cytosol of living cells. Transduction of the protease caspase 3 induced apoptosis in two cancer cell lines, demonstrating that this new protein delivery method could be used to interfere with cellular functions.     

Methodische Untersuchungen zur Erythrozytenfiltration durch Polycarbonatfilter

Zusammenfassung Erythrozyten-Filtrationsmethoden mit Mikro-Porenfiltern aus Polycarbonat können als genaue und zugleich einfache Methoden zur Messung der mittleren Flexibilität von Erythrozytensuspensionen angesehen werden. Unter Beachtung bestimmter Voraussetzungen sind störende Nebeneffekte wie Aggregationsneigung der Erythrozyten und Eigenviskosität des Plasmas weitgehend eliminierbar, so daß die Fließrate (Durchflußmenge/Zeit) einer Erythrozytensuspension als ein Maß für die mittlere Erythrozytenflexibilität angesehen werden kann.Zum Ausschluß von Veränderungen der Erythrozytenflexibilität durch Alterung sollte die Messung innerhalb eines Zeitraumes von ca. 2 Stunden bei 37°C nach Blutentnahme durchgeführt werden.Zur Eliminierung der Eigenviskosität der Blutprobe, besonders durch unterschiedliche Fibrinogenkonzentrationen verschiedener Plasmen, sollten die Erythrozyten in einer definierten Albuminlösung suspendiert werden.Zur Reduktion von Erythrozyten-Aggregationsvorgängen, die eine meßtechnische Differenzierung zwischen Desaggregation und Flexibilität erschweren, sollte die Erythrozytensuspension auf ein Haematokrit zwischen 5 bis 10 Vol.% eingestellt werden.

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Summary Erythrocyte filtration methods by means of polycarbonate micropore filters are an exact and simple technique for measuring the mean flexibility of red blood cell suspensions. Provided that certain precautions are taken, disturbances such as aggregation of erythrocytes and intrinsic plasma viscosity can be eliminated. Thus, the flow rate of an erythrocyte suspension can be used to estimate the mean erythrocyte flexibility.In order to exclude aging, measurements should be done within two hours after blood sampling. To eliminate intrinsic viscosity, especially due to different plasma fibrinogen concentrations, the red blood cells should be suspended in a defined albumin solution.To limit erythrocytes aggregation, which disturbs the differentiation between desaggregation and flexibility of erythrocytes, the red blood cell suspensions should be standardized to an hematocrit of 5–10%.

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Vortrag, gehalten auf der Jahrestagung der Deutschen Rheologischen Gesellschaft in Berlin vom 8.–10. Mai 1978.

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Mit 9 Abbildungen     

Disassembly‐Driven Fluorescence Turn‐on of Polymerized Micelles by Reductive Stimuli in Living Cells

Stimuli‐response nanoparticles have emerged as powerful tools for imaging and therapeutic applications. Ideally, they should be assembled from biodegradable materials featuring small size and cooperative response to biological stimuli that trigger particle disassembly and release of an active molecule that could be readily monitored in situ. A concept is developed that consists of organic nanoparticles, assembled from fluorescent amphiphiles and polymerized with a redox‐cleavable cross‐linker. We obtained 20 nm nanoparticles bearing self‐quenched Nile Red dye residues, which can disassemble in living cells into highly fluorescent molecular units owing to an external or internal reductive stimulus. The obtained results pave the way to new stimuli‐responsive nanomaterials for applications in background‐free imaging as well as in drug delivery, as the concept can be further extended to other active molecules including drugs and to cross‐linkers cleavable by other biological stimuli.