The purpose of this study was to determine the absorption, distribution and excretion of 99m technetiumlabeled, high-molecular-weight hyaluronan (( 99m Tc-P. Urinary and fecal excretion after 99m Tc-HA ingestion by rats showed 86.7-95.6% of radioactivity was recovered, almost all in feces. All tissues examined showed incorporation of radioactivity from 99m Tc-HA starting at 15 min and persisting for 48 h, in a pattern significantly different from 99m Tc-P. Wholebody scintigraphs and close-ups of the ventral chest region showed nonalimentary radioactivity from 99m Tc-HA concentrated in joints, vertebrae and salivary glands four hours after administration. Autoradiography of skin, bone and joint tissue pieces after 24 h showed incorporation of radioactivity from 99m Tc-HA, but not from 99m Tc-P. Conversely, absorption, distribution and excretion of 99m Tc was completely different from 99m Tc-HA, showing an expected pattern of rapid absorption and excretion in urine, with accumulation in thyroid glands, stomach, kidney and bladder. This report presents the first evidence for uptake and distribution to connective tissues of orally administered, high-molecularweight HA.
Premature polymerization of flagellin (FliC), the main component of flagellar filaments, is prevented by the FliS chaperone in the cytosol. Interaction of FliS with flagellin was characterized by isothermal titration calorimetry producing an association constant of 1.9 · 10 7 M À1 and a binding stoichiometry of 1:1. Experiments with truncated FliC fragments demonstrated that the C-terminal disordered region of flagellin is essential for FliS binding. As revealed by thermal unfolding experiments, FliS does not function as an antifolding factor keeping flagellin in a secretion-competent conformation. Instead, FliS binding facilitates the formation of a-helical secondary structure in the chaperone binding region of flagellin.
The present article describes the preparation, characterization, and biological evaluation of Thulium-170 ((170)Tm) [T1/2 = 128.4 days; Eβmax = 968 keV; Eγ = 84 keV (3.26%)] labeled tin oxide microparticles for its possible use in radiation synovectomy (RSV) of medium-sized joints. (170)Tm was produced by irradiation of natural thulium oxide target. 170Tm-labeled microparticles were synthesized with high yield and radionuclidic purity (> 99%) along with excellent in vitro stability by following a simple process. Particle sizes and morphology of the radiolabeled particles were examined by light microscope, dynamic light scattering, and transmission electron microscope and found to be of stable spherical morphology within the range of 1.4-3.2 μm. The preparation was injected into the knee joints of healthy Beagle dogs intraarticularly for biological studies. Serial whole-body and regional images were taken by single-photon-emission computed tomography (SPECT) and SPECT-CT cameras up to 9 months postadministration, which showed very low leakage (< 8% of I.D.) of the instilled particles. The majority of leaked radiocolloid particles were found in inguinal lymph nodes during the 9 months of follow-up. All the animals tolerated the treatment well; the compound did not show any possible radiotoxicological effect. These preliminary studies showed that 170Tm-labeled microparticles could be a promising nontoxic and effective radiopharmaceutical for RSV applications or later local antitumor therapy.
On the basis of a detailed analysis, the correlation between the number of treatments, the therapeutic and the side effects could be verified. In the course of dose reduction, there was no significant difference when comparing the results of therapy, however, the quality of life was better if cisplatin 30 mg/m(2) was administered instead of 40 mg/m(2). If cisplatin 20 mg/m(2) was given, the results were significantly worse. On the basis of the own results, it can be stated that the optimal weekly dose of cisplatin is 30 mg/m(2).
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