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Abstract: Recently, the feasibility of the praseodymium complex of 10-(2-methoxyethyl)-1,4,7,10-tetraaza-cyclododecane-1,4,7-triacetate (Pr[MOE-DO3A]) for non-invasive temperature measurement via1H spectroscopy has been demonstrated. Particularly the suitability of the complex for non-invasive temperature measurements including in vivo spectroscopy without spatial resolution as well as first spectroscopic imaging measurements at low temporal resolution (≥4 min) and high temporal resolution (breath hold, ∼20 s) has been shown. As of today, calibration curves according to the particular experimental conditions are necessary. This work aims to clarify whether the Pr[MOE-DO3A] probe in conjunction with1H-NMR spectroscopy allows non-invasive absolute temperature measurements with high accuracy. The measurement results from two different representative media, distilled water and human plasma, show a slight but significant dependence of the calibration curves on the surrounding medium. Calibration curves in water and plasma were derived for the temperature dependence of the chemical shift difference (F) between Pr[MOE-DO3A]'s OCH3 and water withF=−(27.530.04)+(0.1250.001)* T andF=−(27.610.02)+(0.1290.001)* T. respectivel, withF in ppm andT in C. However, the differences are minuscule even for the highest spectral resolution of 0.001 ppm/pt, so that they are indistinguishable under practical conditions. The estimated temperature errors are 0.18C for water and 0.14C for plasma and with that only slightly worse than the measurement accuracy of the fiber-optical temperature probe (0.1C). It can be concluded that the results obtained indicate the feasibility of the1H spectroscopy method in conjunction with the Pr[MOE-DO3A] probe for absolute temperature measurements, with a maximum accuracy of 0.2C.

B16-melanoma-bearing mice were treated with four different formulations containing equivalent doses of the highly effective antineoplastic drug mitoxantrone. The formulations were: A mitoxantrone solution, a negatively charged liposome preparation (small unilamellar vesicles), a14C-labeled polybutylcyanoacrylate- (PBCA) nanoparticle suspension, and a suspension of poloxamine 1508-coated14C-PBCA-nanoparticles. After 1, 4 and 24 hr, three animals of each group were killed and the mitoxantrone concentrations in the blood, tumor, liver, spleen, heart and bone marrow were determined using an high performance liquid chromatography technique. Additionally, the concentrations of PBCA particles in the same tissues were measured by scintillation counting to compare the mitoxantrone distribution with the corresponding PBCA nanoparticle distribution. Each formulation led to a different body distribution profile of the drug. Liposomes drastically increased the blood level of mitoxantrone even after 24 hr, although free drug was cleared quickly. Liposomes also raised the concentration in the liver and spleen, but not the drug level in the tumor. PBCA-nanoparticles considerably increased the mitoxantrone concentrations in tumor, heart and spleen. However, the increase in tumor concentrations was not statistically significant due to the high variability. Nevertheless, the tumor growth was reduced significantly (P < .05) compared to both, the liposome and the solution preparation. The nanoparticle polymer concentrations did not completely mirror those of the drug concentrations. Especially in the heart, where no nanoparticle polymer radioactivity was found, the particle concentration did not completely correspond to the mitoxantrone concentration, revealing that a part of the drug was lost from the particles. These pharmacokinetic results correspond to parallel therapeutic effects obtained with mitoxantrone-loaded nanoparticles and liposomes in the B16 melanoma.

Urinary excretion of endothelin was measured by radioimmunoassay in children with diabetes mellitus during severe ketoacidosis and 12 days later when blood pH and blood glucose concentrations were normal. Metabolically stable diabetic children served as controls. Results from apparently healthy children without diabetes mellitus were used as normal values. Renal tubular injury was evaluated by the urinary excretion of the proximal tubular marker a1-microglobulin and the distal tubular marker Tamm-Horsfall protein (THP). During ketoacidosis we detected a decreased glomerular filtration rate associated with highly significant changes in the excretion of a1-microglobulin, indicating proximal tubular damage, and THP, suggesting disturbance of cells of the ascending loop of Henle. The daily excretion of endothelin was unaltered but the ratio of endothelin/creatinine or endothelin excretion/creatinine clearance were significantly enhanced. In conclusion, we could demonstrate that, despite a proximal and distal tubular cell dysfunction, endothelin excretion when related to creatinine clearance may be a consequence of disturbed proximal tubular function or dysfunction of the renal medulla.

It is the aim of this paper to demonstrate that much information is to be obtained about lameller systems when diffraction work is performed on well aligned samples and paracrystal methods are applied. There is no need to examine "crytallized" monohydrates in order to get more diffractio spots. Contrary to this, a water cotent above 20% is of higherbiological relevance. The water content of 23 wt.% wasd introduced by swelling in the gel-phase, giving a bigger stackign period than usually reported, when swelling is performed in the Lα-phase. At various temperatures oriented "multi-sandwiches" of dipalmitoyl lecithin (DPL) multilayers were analyzed by small-and wide angle X-ray diffraction as party reported before. Thus, in the gel-phase the tilt angle θ of the hydrocarbon chains can directly be measured, and moreover it is proved that the chains are tilted by 7° to 15° in b-direction of the orthorhombic and the hexagonal lattice. 012-[paraffine netplanes sablize a well-defined membrane surface like the 201-planes in Cerebrosides. Contary to paraffins the c/2 steps of the CH2-chains along the b-direction are only a statistical average. These steps roughen the lamellae surfaces and produce paracrystalline distortions of g ∼ 2.4% of the long period in the gel-phase. In the Pβ-phase and the CH2-chains are laterally paracrystallien distored with g ∼ 10% and the membrane surfaces become smooth because molecular dynamics hinder the chains from latching on to eachother, and the long period, before therefore, is crystalline-like. Astbury's remarks on the interplay of order-disorder between molecular and supermolecular structures is fulfilled inm a special way. In addition the a*-law, which combines the size of the lamellae bundles withtheir g-values also is fully confirmed.Below 35°C the hydrocarbon lattice is orthorhombic with a 1 % deviation from the hexagonal case. Only near 0°C undergoing the "subtransition" is the lattice similar to paraffins, and the tilt angle is reduced. The Ps-phase is characterized by a hexagonal hydrocarbon lattice accompanied by the wellknown "ripples" which take the direction of the a-axis, making them orthogonal to the molecular tilt direction. Contraty to the findings of others our "weak" ripples produce no equoatorial reflection in the small angle region, explained by the lack of longitudinal density fluctuations. A profound theoreical calculation of the weights of the humps at the long period tails yeilds ripple waves with a mean wave length of the humps at the long period tails yields ripple waves with a mean wave lenght of 310 ± 30 and an amplitude (4.5 ± 0.5) Å. The wave lingths here vary to such a large amount that the small angle pattern offers no distinct isolated lateral spots. This is explained by the multi-sandwich preparation which hinders their free development. The analysis, with help of uncorrelated step dislocations, leads to a paracrystalline value of gexp = 10%.

The thermotropic phases of fatty acid (C12, C14, C22) thallium (I) salts were studied by the spin-1/2-pair dipolar echo 1H-NMR method and by 205Tl-NMR in the temperature range from 230 K to 480 K. For the first time the 205Tl chemical shift tensor in such soaps in the crystalline state was shown to be axially symmetric and to exhibit an anisotropy of -780 ± 8 ppm. Also for the first time, a detailed characterization of the dynamical properties of the liquid crystalline mesophases was performed; this allows some conclusions to be reached about the structure of the mesophases present in the C12 and C14 soaps below their isotropic states. The phases of the various soaps studied were unambiguously assigned.

A model system of perfused human colon adenocarcinoma cells (HT29) encapsulated in alginate was used to examine metabolic response to heat therapy with 31P NMR spectroscopy, HPLC and cell survival analysis. The presented data show, that perfused (medium flow during hyperthermia) and non-perfused (no medium flow during hyperthermia) cells are very different in their sensitivity to hyperthermia. Under equivalent experimental conditions with respect to medium pH, oxygen and nutrient concentration, encapsulated perfused HT 29 cells display a significantly lower thermal sensitivity than non-perfused cells. This reduced sensitivity of perfused cells is characterized by an increased cell survival and relative ATP concentration. and reduced drop of the NTP/Pi ratio in the long-term follow up towards zero. The relative ATP concentration determined by HPLC after hyperthermia is correlated with the clonogenic survival fraction. There is a direct relationship, depending on the specific experimental conditions (perfused, non-perfused). For perfused cells only a slight dependency of survival and relative ATP concentration on heat dose is observed. In consequence, the correlation between survival and relative ATP concentration is weak, described by log(SFperf)=0.7*[ATP]-12.4, R2 = 0.79, p < 0.04. For non-perfused cells the correlation is stronger resulting in a relationship of log(SF no perf) = 0.6*[ATP]-9.0, R2 =0.98, p < 0.0002. Altogether, the presented data suggest that the relative ATP concentration measured by HPLC after hyperthermia might be predictive for cell survival. On the other hand, a dependence between cell survival and long-term changes of NTP/Pi has been found. The results confirm the importance of tumour perfusion for hyperthermia-induced metabolic changes and cytotoxicity and therefore, for the therapeutic outcome.

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