Animal models for treatment of unresectable liver tumours: a histopathologic and ultra-structural study of cellular toxic changes after electrochemical treatment in rat and dog liver

INTRODUCTION: Electrochemical treatment (EChT) has been taken under serious consideration as being one of several techniques for local treatment of malignancies. The advantage of EChT is the minimal invasive approach and the absence of serious side effects. Macroscopic, histopathological and ultra-structural findings in liver following a four-electrode configuration (dog) and a two-electrode EChT design (dog and rat) were studied. MATERIALS AND METHODS: 30 female Sprague-Dawley rats and four female beagle dogs were studied with EChT using Platinum:Iridium electrodes and the delivered dose was 5, 10 or 90 C (As). After EChT, the animals were euthanized. RESULTS: The distribution of the lesions was predictable, irrespective of dose and electrode configuration. Destruction volumes were found to fit into a logarithmic curve (dose-response). Histopathological examination confirmed a spherical (rat) and cylindrical/ellipsoidal (dog) lesion. The type of necrosis differed due to electrode polarity. Ultra-structural analysis showed distinct features of cell damage depending on the distance from the electrode. Histopathological and ultra-structural examination demonstrated that the liver tissue close to the border of the lesion displayed a normal morphology. CONCLUSIONS: The in vivo dose-planning model is reliable, even in species with larger tissue mass such as dogs. A multi-electrode EChT-design could obtain predictable lesions. The cellular toxicity following EChT is clearly identified and varies with the distance from the electrode and polarity. The distinct border between the lesion and normal tissue suggests that EChT in a clinical setting for the treatment of liver tumours can give a reliable destruction margin.     

NMR spectra of a microcrystalline protein at 30 kHz MAS

Proteins are not always available in amounts desirable for solid-state magic-angle spinning (MAS) nuclear-magnetic resonance (NMR) spectroscopy. To maximize the signal-to-noise ratio achievable with small samples, the filling factor must be optimized by using small-diameter MAS rotors. These rotors have the added benefit of allowing higher radio frequency field amplitudes during polarization transfer steps and during decoupling periods as well as allowing higher spinning frequencies. We demonstrate the advantages of relatively fast MAS (30 kHz using a 2.5 mm rotor) compared to MAS at 12 kHz for the 10.4 kDa model protein Crh with 93 residues and show that the signal-to-noise ratio in two-dimensional correlation spectra can be significantly improved by taking advantage of optimized pulse sequences available with rapid MAS.     

Photoinduced electron transfer in platinum(II) terpyridinyl acetylide complexes connected to a porphyrin unit

A series of six new dyads consisting of a zinc or magnesium porphyrin appended to a platinum terpyridine acetylide complex via a para-phenylene bisacetylene spacer are described. Different substituents on the 4' position of the terpyridinyl ligand were explored (OC7H15, PO3Et2, and H). The ground-state electronic properties of the dyads are studied by electronic absorption spectroscopy and electrochemistry, and they indicate some electronic interactions between the porphyrin subunit and the platinum complex. The photophysical properties of these dyads were investigated by steady-state, time-resolved, and femtosecond transient absorption spectroscopy in N,N-dimethylformamide solution. Excitation of the porphyrin unit leads to a very rapid electron transfer (2-20 ps) to the nearby platinum complex followed by an ultrafast charge recombination, thus preventing any observation of the charge separated state. The variation in the rate of the photoinduced electron transfer in the series of dyads is consistent with Marcus theory. The results underscore the potential of the para-phenylene bisacetylene bridge to mediate a rapid electron transfer over a long donor-acceptor distance.     

Studies on the conversions of diols and cyclic ethers—49: Stereochemistry of cyclodehydration of 1,4-diols on the action of brönsted and lewis acids: a comprehensive study

The stereochemistry of the cyclodehydration of (±)- and meso-2,5-hexanediol on the action of various dehydrating agents was investigated. The earlier assumed and confirmed intramolecular S_N2 mechanism for acid-catalysed ring-closure was found to hold in most cases. Various extents of racemisation can be observed on the action of certain Lewis acids, and the solvents concentrated H₂SO₄ and HMPT (hexamethyl phosporic acid triamide) under previously unexamined reaction conditions.     

Development of a quick leaching test for monolithic materials by using factorial design

A quick leaching test procedure for monolithic waste materials has been developed by a Nordic expert group using experimental factorial design. The Dutch quick leaching test proposal in which the wetting time of the test specimen is reduced by applying vacuum was chosen as a starting point. The influence of the following parameters were studied: vacuum, stirring, open or closed vessel, water renewal frequency, leachant quality and laboratory or batch differences. The study was performed with test specimens prepared from a cement stabilised soil containing As, Cr and Cu. The test specimens were immersed in water and the water was renewed at certain time intervals. The study clearly showed that the use of vacuum had a strong effect on the release rate and that the open vessel lowered the pH-values of the eluates due to uptake of carbon dioxide in the water. The results also indicate higher emissions when stirring was applied. The following test conditions are recommended: application of vacuum prior to testing, use of closed test vessel, use of stirring, a test time of 3 days with four water renewals after 15 min vacuum steps, and then after e.g. 2 h, 23 h and 3.2 days, use of demineralised water as leachant. The amount of water must be selected according to the size of the test specimen. A liquid to surface (L/A) ratio of 5-10 ml cm(-2) is recommended. All four eluates collected are filtered and analysed.     

Implementation of traceability – needs and perspective of the in-vitro-diagnosticum industry

Manufacturers support the concept of traceability. However, only a small number of the medically relevant measurands can be traced to the highest metrological order. In many cases, the measured substances are heterogeneous mixtures where traceability can be established only to either an international conventional reference measurement procedure or to a manufacturers own in-house reference system. The traceability concept needs to be seen in the context that the results of medical laboratories are not an aim per se, but are meant to provide useful medical information to clinicians, and that pre- and post-analytical steps may also contribute significantly to errors. There is a need for the further development of suitable reference measurement systems, but in view of the multitude of tasks and limited resources, priorities need to be set.Presented at BERM-9 – 9^th International Symposium on Biological and Environmental Reference Materials, 15–19 June 2003, Berlin, Germany     

Dynamic microwave-assisted extraction coupled on-line with solid-phase extraction: determination of polycyclic aromatic hydrocarbons in sediment and soil

This paper describes a new extraction tool for the determination of polycyclic aromatic hydrocarbons (PAHs) in soil and sediment samples, using dynamic microwave-assisted extraction combined with solid-phase extraction (DMAE-SPE). The critical variables for DMAE-SPE are investigated and optimized in an experimental design. The technique proved to be fast, accurate and able to yield quantitative extraction of PAHs from naturally contaminated sediment and soil samples. The set-up is fully automated and features monitored extraction, which facilitates rapid optimization of the method. In addition, only small quantities of solvent and sample are required.     

The simplest coronoids: Hollow hexagons

Hollow hexagons form a subclass of primitive coronoid systems. The macrocyclic aromatic hydrocarbon kekulene corresponds to a hollow hexagon. The hollow hexagons for given numbers of hexagonal units (h) were enumerated by computer aid, but also an analytical solution for the numbers of hollow hexagons was achieved. For the Kekulé structure counts (k) of a hollow hexagon a general formula is reported. Also the maximum and minimumK numbers are considered.This article is Part VI of the series Enumeration and Classification of Coronoid Hydrocarbons. For Part V, see ref. [36].     

Regiospecific synthesis of mono-N-substituted indolopyrrolocarbazoles

[reactions: see text] Two complementary and efficient strategies have been developed for the regiospecific synthesis of unsymmetrical indolopyrrolocarbazoles (IPCs) mono-N-substituted with a pentacycle. A halogen in position 2 of the intermediate bisindolylmaleimides 3a-e allows a selective Mitsunobu coupling by exploiting the increased acidity of the 2-chloro-substituted indole nitrogen. It also promotes an easier cyclization of bisindolylmaleimides 4a-e and 7b-e to IPCs. Alkylation of the 2-unsubstituted indole-3-carboxamides 2a,b and further processing to the corresponding IPCs gives access to the opposite regioisomers.     

A recycling technique for the chromatographic separation of enantiomers and diastereomers on triacetylcellulose

A simple and inexpensive equipment for the optical resolution of enantiomers (and separation of diastereomers) on triacetylcellulose in ethanol at elevated pressure is described. It involves a closed circuit of solvent (pump—column—detector—pump) allowing a continuous chromatography up to 16 cycles without stopping the flow or handling fractions.This useful and versatile method permitting also the determination of enantiomeric purities is illustrated by several examples of centro-, axial- and planarchiral arenes and metallocenes.Herrn Prof. Dr.U. Schmidt, Stuttgart, zum 60. Geburtstag gewidmet.