Messung der Leberschädigung durch Perchlorethen mit Hilfe des in vivo [15N]Methacetin-Urintests

Es wird gezeigt, daß der [¹⁵N]Methacetin-Urintest ein empfindliches, einfaches und nicht belastendes Verfahren ist, mit dem hepatozelluläre Schädigungen als Folge bestimmter Umwelteinflüsse am Arbeitsplatz gemessen werden können.

Die Methode wird an 13 Textilreinigerinnen demonstriert, die bis zu 39 Jahre in ihrem Betrieb Perchlorethendämpfen ausgesetzt waren.

Mit zunehmenden Expositionszeiten der Arbeiterinnen nehmen die ¹⁵N-Eliminations-geschwindigkeiten absinkenden hepatozellulären Monooxygenasen-Kapazitäten. Dies entspricht.

It is shown that the [¹⁵N]methacetin urine test is a sensitive, simple, and non-distressing tool to measure hepatocellular injury as a consequence of certain environmental factors at the workplace.

The method is demonstrated with 13 female textile cleaners who have been exposed to perchlorethylene for up to 39 years in their shop.

Decreasing ¹⁵N elimination rates – equal to decreasing monooxygenase capacities – are seen to be correlated with increasing exposure times of the workers.     

Viscoelastic properties of ultra-high viscosity alginates

Ultra-high viscosity alginates were extracted from the brown seaweeds Lessonia nigrescens (UHV_N, containing 61% mannuronate (M) and 2% guluronate (G)) and Lessonia trabeculata (UHV_T, containing 22% M and 78% G). The viscoelastic behavior of the aqueous solutions of these alginates was determined in shear flow in terms of the shear stress σ ₂₁, the first normal stress difference N ₁, and the shear viscosity η in isotonic NaCl solutions (0.154 mol/L) at T = 298 K in dependence of the shear rate [(g)\dot]\dot{\gamma} for solutions of varying concentrations and molar masses (3–10 × 10⁵ g/mol, homologous series was prepared by ultrasonic degradation). Data obtained in small-amplitude oscillatory shear (SAOS) experiments obey the Cox–Merz rule. For comparison, a commercial alginate with intermediate chemical composition was additionally characterized. Particulate substances which are omnipresent in most alginates influenced the determination of the material functions at low shear rates. We have calculated structure–property relationships for the prediction of the viscosity yield, e.g., η–M _w–c–[(g)\dot]\dot{\gamma} for the Newtonian and non-Newtonian region. For the highest molar masses and concentrations, the elasticity yield in terms of N ₁ could be determined. In addition, the extensional flow behavior of the alginates was measured using capillary breakup extensional rheometry. The results demonstrate that even samples with the same average molar mass but different molar mass distributions can be differentiated in contrast to shear flow or SAOS experiments.     

Flexible but with a defined turn-influence of the template on the binding properties of two-armed receptors

Combinatorial binding studies revealed that the di(trans-4-aminoproline)diketopiperazine is an ideal template for two-armed receptors with highly selective binding properties towards peptides. It is not only superior to structurally very different diamines but also to the diastereomeric di(cis-4-aminoproline)diketopiperazine. These empiric results are rationalized by the analysis of the conformation of the diastereomeric diketopiperazines in the solid state, by X-ray crystal structure analysis, as well as by NMR studies in solution: to observe highly selective binding, the template needs to be not only conformationally rigid but it must have a specific turn geometry. The combination of combinatorial binding studies, X-ray crystal structure analysis, and NMR spectroscopy gave insight into why the trans,trans-diketopiperazine is a superior template compared to other diamines. Additionally, the results provide a guide for the rational design of two-armed receptors with good binding properties towards peptidic guests.     

Rheologie pathologischer Gelenkflüssigkeiten

Zusammenfassung Zur Charakterisierung der Lösungsstruktur pathologischer Synovialflüssigkeiten wurden parallel rheologische Untersuchungen sowohl im Bereich konzentrierter als auch verdünnter Lösungen durchgeführt. Durch die Berücksichtigung der Scherabhängigkeit der Grenzviskositätszahl [] und Messung bei niedrigen Schergeschwindigkeiten (D 2,9 10^–3 – 4,6 s^–1) errechneten sich höhere Molekulargewichte der Hyaluronsäure (HA) als bisher angegeben. Für entzündliche Gelenkergüsse betragen sie (2,4–12,0) 10⁶, für nicht entzündliche (3,1–11,4) 10⁶ und sind damit gegenüber der normalen Synovia mit 16,2 10⁶ erniedrigt. Unterschiedlichek _SB-Werte sprechen zusätzlich für eine stärkere Verknäuelung der HA-Makromoleküle in der pathologischen Synovia.Durch Ermittlung der kritischen Polymerkonzentration der HA sowie der Verhängungszahlenv aus Anlaufmessungen konnten quantitative Aussagen zum makromolekularen Netzwerk getroffen werden. Die normale Synovia entspricht einem sehr engmaschigen und dichten Netz, aber auch in den pathologischen Gelenkflüssigkeiten ist die HA nicht im Sinne einer Partikellösung isoliert, sondern bildet ein, wenn auch lockeres Netzwerk mit wesentlich niedrigerer Verhängungszahl. Eine Erniedrigung der Viskosität und Elastizität isolierter HA weist darauf hin, daß molekulare Wechselwirkungen zwischen HA und anderen Makromolekülen in der Synovialflüssigkeit für das rheologische Verhalten von wesentlicher Bedeutung sind. Relaxationszeitmessungen in Ruhe und unter Scherung zeigten eine vermehrte Segmentbeweglichkeit des Netzwerkes der pathologischen Synovia als Folge der HA-Konzentrationsabnahme und/oder Molekulargewichtsverminderung.

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Summary Rheological investigations were done in concentrated as well as diluted solutions to characterize the solution structure of pathological synovial fluids. By looking at the shear rate dependence of [] at low shear rates (D 2,9 10^–3 – 4,6 s^–1) higher molecular weights were determined than reported before. The so determined molecular weights of hyaluronic acid (HA) are in the range ofM = 2,4 10⁶–12 10⁶ g/mol in inflammatory joint diseases and in non-inflammatory in a range ofM = 3,1 10⁶–11,4 10⁶ g/mol and therefore both are lower than in normal synovial fluids,M = 16,2 10⁶ g/mol. Additional distinctk _SB-values indicate a compacter coil of HA macromolecules in the pathological synovial fluid.Quantitative statements can be made to the macromolecular network structure by determination of the critical HA polymer concentration and the number of entanglements resulting from prestationary measurements. The normal synovial fluid is comparable with a very narrow-meshed and dense network, but also in the pathological synovial fluid the HA is not isolated like in a particle solution but forms a much looser entanglement network structure. The reduction of viscosity and elasticity of isolated HA indicate that molecular interactions between HA and other macromolecules in synovial fluid are of essential significance for the rheological behaviour. Measurements of relaxation time at rest as well as shear conditions show a higher segment-flexibility of macromolecular network structure resulting from a reduction of HA-concentration and/or molecular weight in the pathological synovial fluid.

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D Schergeschwindigkeit - D _K D-Koordinate des Tangentenschnittpunktes der Fließkurve - t _k Knickzeit (Relaxationszeit) - scheinbare Viskosität (Scherviskosität) - ₀ Anfangs-, Nullviskosität - _rel relative Viskosität - _sp spezifische Viskosität - _red = _sp/c reduzierte Viskosität - [] Grenzviskositätszahl (Staudinger-Index) - A Flächenmaß der master-curve - G ₀ Ruheschermodul - G _s Schermodul der strömenden Lösung - _N = ₁₁ – ₂₂ erste Normalspannungsdifferenz - ₁₂ Schubspannung - ₀ scheinbare Relaxationszeit der ruhenden Lösung - scheinbare Relaxationszeit der strömenden Lösung - v Verhängungszahl - M Molekulargewiht - s ₂₀ Sedimentationskoeffizient bezogen auf 20°C - s ₂₀ ⁰ Sedimentationskoeffizient bezogen auf 20°C bei unendlicher Verdünnung (c 0) - c Hyaluronsäure-Konzentration - c _krit kritische Hyaluronsäure-Konzentration - c _p Protein-Konzentration - _äqu Dichte äquivalenter Kugeln - Dichte des Mediums im Kegel/Platte-Spalt - Winkelgeschwindigkeit - R Radius von Kegel und Platte des Meßsystems - r Korrelationskoeffizient - p Signifikanzniveau Herrn Prof. Dr. med.Fritz Hartmann zu seinem 60. Geburtstag gewidmet.Mit 14 Abbildungen und 5 Tabellen     

Improvements in Polysaccharides for use as Blood Plasma Expanders

Modern blood plasma volume expanders consist of water-soluble polysaccharides that are compatible with the human body. They are more effective for the treatment of intravasal volume deficiency compared to synthetic polymers. These colloidal blood plasma volume expanders, for example pullulan, dextran or hydroxyethyl starch (HES) are used in blood isotonic electrolyte solutions. HES has the lowest tendency to remain in the liver or other organs of the human body in comparison to other expanders. The knowledge of the molar mass and coil dimensions as well as their distribution are essential, since products of low molar masses do not have the desired effect and parts of large molar masses can lead to an anaphylactic shock. Injection of HES enhances the microcirculation and leads to a better oxygen transport into the tissue and the muscle. Because of this, HES was identified as a doping agent in 02/2002. In addition to this it will be shown that starch acetates have an even better physiological compatibility and are an interesting alternative to HES. We will present investigations on the shelf life of a new acetyl starch, which may be an alternative to the blood plasma expanders used to date.     

Characterization and flow properties of lyotropic ultrahigh-molar-mass polysaccharide mesophases

The occurrence of lyotropic mesophases in solutions of various polysaccharides, such as non-ionic schizophyllan and anionic xanthan, was demonstrated by means of polarizing microscopy. In contrast to synthetic polymers where the formation of liquid-crystalline phases has been attributed to the presence of mesogenic groups in the main- or side-chain, here a helical structure is a prerequisite for the formation of mesophases. It was then shown that the stability of the helix is dependent on the chemical structure and the arrangement of the side groups. Apart from their optical anisotropy, some lyotropic mesophases are distinguished by extraordinary viscous and elastic properties (e.g. maximum behaviour of viscosity). The viscoelastic material functions were determined by rheological methods. A precise characterization of the chemical and steric microstructure should provide information on the ability of polysaccharides to form mesophases. Determination of the chemical microstructure (quaternary polymer) was carried out by ¹H NMR spectroscopy after ultrasonic degradation. Low- and multi-angle laser light scattering were employed for the determination of the steric microstructure which indicates an expanded semi-flexible structure. The experimental results were compared with those from molecular modelling.     

Rheological characterization of the dilatant flow behavior of highly substituted hydroxypropylmethyl- cellulose solutions in the presence of sodium lauryl sulfate

 The flow behavior of aqueous solutions of three highly substituted, hydrophobic hydroxypropylmethylcelluloses (HPMC) in mixtures containing the anionic surfactant sodium lauryl sulfate (SLS) was investigated both rheo-mechanically and rheo-optically. For the first time it was possible to demonstrate dilatant flow in these systems, a phenomenon which is otherwise only known of some suspensions and associative thickening solutions. Without addition of SLS, the aqueous HPMC solutions showed the predicted flow behavior of polymer solutions, and the Cox–Merz rule was fulfilled. With the addition of SLS to these HPMC solutions, the least hydrophobic HPMC displayed no dilatancy. The solutions of a more hydrophobic HPMC with SLS exhibited on the one hand an increase in viscosity, and on the other hand shear thinning as well as shear thickening. The most hydrophobic HPMC displayed more clearly the effects of an SLS-dependent viscosity increase and the appearance of dilatant flow. At constant HPMC concentration (0.5% w/w), a maximum increase in viscosity (factor 15) was observed in the critical micelle concentration range for SLS. By rheo-optical measurements it was possible to detect an unusually pronounced alignment of the polymer segments as well as a sharp increase in the birefringence values, even before the macroscopic occurrence of dilatant flow. According to the existing network theories, this behavior of the aqueous solutions of highly substituted HPMCs in mixture with SLS has been interpreted as a shear-induced transition from intra-molecular to intermolecular interactions. Received: 4 February 1998 Accepted: 13 March 1998     

Cationic starches as substitute for synthetic cationic flocculants in solid-liquid separation of harbor sludge

Harbor sludge (about 25% total solid) has to be dredged to keep the waterways free. Thus, annually 1.2 million m3 of dredged material has to be cleaned. For this process, three different synthetic flocculants with optimal molar masses, ionogenities, and concentrations are added in order to get a good dewatering efficiency and shear strength of the flocs. But as synthetic flocculants bring about unwanted fish toxicity and insufficient biodegradability, this study intends to check whether these flocculants can successively be substituted by cationic starches which have already been proven to be less toxic than synthetic flocculants. Five different starch derivatives with an average degree of substitution higher than 0.5 were characterized, especially in terms of the molar mass and coil size distribution, and flocculation tests, zeta potential measurements and filtrate turbidity tests were carried out in order to create optimum flocculation conditions. The flocculation and dewatering measurements clearly show that the synthetic cationic flocculant PA (0.2 kg/tTS) can be best substituted by cationic starch KS 2 (c = 0.1 kg/tTS, Mw = 1.1 e+08). For substitution of PTAC (c = 0.3 kg/tTS) by cationic starches, we observed that a maximal dewatering efficiency is reached with an approximately 3-fold dose of KS 1 (1 kg/tTS, Mw = 8.1 e+07).