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[en] Despite numerous studies that report the glucose derived glycoconjugates as antitumor candidates, using mannose as sugar motif for specific tumor targeting remains less studied. In this research, two novel mannose-conjugated platinum complexes 4a and 4b that target the Warburg effect were designed, synthesized and evaluated for their antitumor activities in vitro and in vivo. Compared with oxaliplatin, both complexes exhibited substantial enhancement in water solubility as well as excellent or comparative cytotoxicity in six human cancer cell lines. Cytotoxicity assessments on Glucose transporter 1 (GLUT1) down-regulated or overexpressed cells and platinum accumulation study demonstrated that cellular uptake of compound 4a was regulated by GLUT1. In particular, 4a induced apoptosis in HT29 cells by suppressing expression of Bcl-2 and Bcl-XL, which preliminary explained the mechanism origin of antitumor effect. As indicated by its maximum tolerated dose-finding assay and in vivo anticancer activity, compound 4a exhibits better safety and efficacy profile than oxaliplatin. The findings of this study indicate the possibility of subjecting mannose-conjugated platinum complexes as lead compounds for further preclinical evaluation. - Highlights: • Mannose-conjugated platinum complexes were designed and synthesized to target glucose transporter 1(GLUT1). • Mannose-conjugated platinum complex 4a transport across cancer cells through GLUT1. • Mannose-conjugated platinum complex 4a induce apoptosis in HT29 cells. • Mannose-conjugated platinum complex 4a antitumor activities were more potent than those of oxaliplatin.
[en] The ZEUS experiment at the electron(positron)/proton collider HERA is planning to replace a small electromagnetic tungsten/scintillator sampling calorimeter by a lead tungstate (PbWO4) crystal calorimeter. The ''beampipe calorimeter'' (BPC) directly adjacent to the beam intercepts electrons with small scattering angles. It measures the inelastic electron-proton scattering in the interesting kinematic region 0.045 ≤ Q2 ≤ 0.80 GeV2 and 3 x 10-7 ≤ x ≤ 10-3 where the transition from photoproduction to deep inelastic scattering occurs. An improvement of the current electromagnetic energy resolution from 17%/√(E/GeV) to 5%/√(E/GeV), which is expected for a PbWO4 calorimeter, would result in a much higher precision of for example the proton structure function F2 and would further extend the accessible kinematic region. The so-called crystal BPC has to meet stringent requirements: the size is restricted, the light yield must be very high, the scintillation light pulses have to be short (95% within 96 ns), and the crystals have to be sufficiently radiation stable. Bench stests have shown that 20 PbWO4 crystals (La doped) with dimensions 200 x 23.8 x 23.8 mm3 which were received in autumn 1997 from BTCP, Bogoroditsk, Russia, fulfil the demands. A full size calorimeter of 4 x 4 crystals has been built and tested in a CERN SPS beam with energies 3-100 GeV. The crystals are read out by small photomultipliers which can work in a magnetic field. A LED transmission monitoring system proved its functionality when two crystals were interchanged with irradiated crystals and the recovery was tracked. (orig.)
[en] Background: Lead remains a considerable occupational and public health problem, which is known to cause a number of adverse effects in both men and women. Conflicting reports have appeared on lead induced nephrotoxicity in experimental studies in the past. There is hardly any work on its teratogenic effects on kidney. Present study was therefore designed to investigate the effects of lead acetate on developing kidney. Methods: Twelve mice were used as experimental model and were divided into two groups of six animals each; group A served as control group and B was used as an experimental group. Lead acetate (10 mg/kg) dissolved in 0.02 ml of distilled water was administered as a single daily dose orally to group B whereas weight related amount of distilled water was given to group A for the entire period of experiment. On 18 day of gestation foetuses were dissected free of uterine wall under the dissecting microscope and were sacrificed; kidneys were removed and fixed in 10% formalin, dehydrated in ascending grades of alcohol, cleared in xylene and infiltrated with filtered paraffin. The paraffin blocks were made and five micron thin sections were obtained using a rotary microtome. The sections were stained with Hematoxylin and eosin and, PAS; these were examined under light microscope. Results: Significant decrease in cortical thickness was observed which varied from 578.6 +- 1.4 mu m in group A to 515.6 +- 5 mu m in group B (p<0.001). Diameter of renal corpuscles varied from 57.7 +- 0.07 mu m in group A to 50.5 +- 0.07 mu m in group B (p<0.001). Moderate cortical tubular atrophy showing thickening of endothelial basement membrane in glomeruli, desquamated epithelium with degenerated nuclei in proximal and distal tubules were observed in group B in contrast to group A. Conclusion: The results of the investigation indicated that lead acetate administration to the dams produced deleterious effects on the developing kidney in mice. (author)
[en] We present the results of an investigation into processes of formation of polar nanoregions and the relaxation dynamics of a cubic relaxor ferroelectric (PbMg1/3Nb2/3O3)0.9-(pbTiO3)0.1 (PMNPT10), selected to be studied as a model compound.
[en] Highlights: • We develop a quantitative ex vivo assay for anti-cataract drug validation. • EC50 values of lanosterol and 25-hydroxycholesterol are at ten micromolar level. • Lanosterol is able to release various human crystallins from the aggregates. • 25-Hydroxycholesterol can only release human α-crystallins. • Lanosterol and 25-hydroxycholesterol are mechanistically different lead compounds. Cataract, a crystallin aggregation disease, is the leading cause of human blindness worldwide. Surgery is the only established treatment of cataracts and no anti-cataract drugs are available thus far. Recently lanosterol and 25-hydroxycholesterol have been reported to redissolve crystallin aggregates and partially restore lens transparency in animals. However, the efficacies of these two compounds have not been quantitatively studied ex vivo using patient tissues. In this research, we developed a quantitative assay applicable to efficacy validations and mechanistic studies by a protocol to isolate protein aggregates from the surgically removed cataractous human lens. Our results showed that both compounds were effective for human cataractous samples with EC50 values at ten micromolar level. The efficacies of both compounds strongly depended on cataract severity. Lanosterol and 25-hydroxycholesterol were two mechanistically different lead compounds of anti-cataract drug design.
[en] A method of removing molybdenum from a uranium bearing solution is claimed. It comprises adding sufficient reactive lead compound to supply at least 90 percent of the stoichiometric quantity of lead ion required to fully react with the molybdenum present to form insoluble lead molybdate and continuing the reaction with agitation until the desired percentage of the molybdenum present has reacted with the lead ion