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[en] Trivalent dimethylarsinous acid [DMA(III)] has been shown to induce mitotic abnormalities, such as centrosome abnormality, multipolar spindles, multipolar division, and aneuploidy, in several cell lines. In order to elucidate the mechanisms underlying these mitotic abnormalities, we investigated DMA(III)-mediated changes in histone H3 phosphorylation and localization of Aurora B kinase, which is a key molecule in cell mitosis. DMA(III) caused the phosphorylation of histone H3 (ser10) and was distributed predominantly in mitotic cells, especially in prometaphase cells. By contrast, most of the phospho-histone H3 was found to be localized in interphase cells after treatment with inorganic arsenite [iAs(III)], suggesting the involvement of a different pathway in phosphorylation. DMA(III) activated Aurora B kinase and slightly activated ERK MAP kinase. Phosphorylation of histone H3 by DMA(III) was effectively reduced by ZM447439 (Aurora kinase inhibitor) and slightly reduced by U0126 (MEK inhibitor). By contrast, iAs(III)-dependent histone H3 phosphorylation was markedly reduced by U0126. Aurora B kinase is generally localized in the midbody during telophase and plays an important role in cytokinesis. However, in some cells treated with DMA(III), Aurora B was not localized in the midbody of telophase cells. These findings suggested that DMA(III) induced a spindle abnormality, thereby activating the spindle assembly checkpoint (SAC) through the Aurora B kinase pathway. In addition, cytokinesis was not completed because of the abnormal localization of Aurora B kinase by DMA(III), thereby resulting in the generation of multinucleated cells. These results provide insight into the mechanism of arsenic tumorigenesis.
[en] Littleseed canarygrass (Phalaris minor) infests wheat and other winter crops in Pakistan and many other countries. Studies were conducted in Pakistan to confirm littleseed canarygrass resistance to fenoxaprop-P-ethyl and to appraise the efficacy of other postemergence herbicides against this grassy weed. A field survey was conducted to collect putative fenoxaprop-resistant seeds from various districts of the central Punjab in March 2015. Dose-response assays were conducted in the greenhouse to confirm resistance to fenoxaprop. The response of fenoxaprop-resistant littleseed canarygrass to diverse herbicide molecules like clodinafop-propargyl, metribuzin, pinoxaden, and sulfosulfuron was also evaluated in further dose-response bioassays. All accessions manifested variable resistance to fenoxaprop, which ranged from 2.52- to 6.00-fold. The resistant accessions also showed low-level cross-resistance (two-fold) to clodinafop. Metribuzin, pinoxaden, and sulfosulfuron were still effective in controlling fenoxaprop-resistant canarygrass. This is the first scientific documentation of resistance to ACCase inhibitor herbicides in central Punjab, Pakistan. The use of alternative herbicides in conjunction with other agronomic practices is crucial for sustainable wheat production in the country. (author)
[en] According to the interaction of unsaturated 5(4H)-oxazolones with 1,1,1,3,3,3-hexamethyldisilazane, have been synthesised 2,4-disubstituted 5(4H)-imidazolones. There where shown, that this compounds can inhibit acetylcholine- and butyrylcholinesterases. From synthesised compounds there was evident the 2-phenil-4-(p-toluolsulfoniloxybenzilidene)-5(4H)-imidazolone as active butyrylcholinesterase inhibitor
[en] Until the turn of the millennium, metastatic renal cell carcinoma (mRCC) was regarded as one of the most refractory cancers; highly resistant to both radiation and systemic therapy, and only small group of patients responded to immune modulation. Involved targeted therapies, which influence specific signal transduction pathways of tumor formation and progression, opened new options of treatment to give patients a new hope. After the first experiences with the new biologic agents we can claim, that these patients have improved a quality of life, provided stabilization of disease and prolong life of patients, but the cure is not available. However, there are so many studies with target therapies in RCC, but the most correct algorithm of treatment does not exist. Targeted therapies rarely achieve remission, prevailing a stabilisation of disease so patients have to undergo chronic treatment. In choice of optimal treatment is necessary to regard for quality of life, so usually the winner is the drug with the lowest toxic potential. (author)
[en] Proteases belong to an important class of enzymes known as hydrolases and catalyze hydrolysis of proteins. They act primarily to degrade proteins that are used for energy production and as biosynthetic precursors. In the following study, protease produced from Aspergillus terreus was found to be thermo stable and included in the category of alkaline serine and metallo protease. During partial purification, presence of enzyme in 60% (NH/sub 4/)/sub 2/SO/sub 4/ indicated small molecular weight polypeptide; later purification with Sephadex G-75 fractionation yielded a single proteolytic active molecule. At final purification step, the increase in specific activity of the enzyme was 7.5 fold with 23% yield. SDS-PAGE analysis revealed that alkaline protease of Aspergillus terreus is a monomer with approximate molecular weight of 35 kDa. Optimum pH for protease activity was found in the range of 7.5-11.0 (maximum at pH 8.5), thus apparently classified as an alkaline protease. The enzyme was thermo stable towards high temperature (60 deg. C), however it denatured irreversibly at 70 deg. C showing 80% loss of activity. The maximum proteolytic activity was found at 40 deg. C. The enzyme was effectively inhibited by PMSF, EDTA and urea whereas iodoacetamide and thiourea did not result in any loss in activity while cysteine was found to be activator molecule. The study with metal ions Mg/sup +2/, Mn/sup +2/ and Fe/sup +3/ (1 mM each) showed minute stimulatory effects on enzyme activity. Co/sup +2/ and Ca/sup +2/ (1 mM) had neither excitatory nor inhibitory effect while Hg/sup +2/ and Cu/sup +2/ (1 mM) slightly reduced the enzyme activity. (author)
[en] Histone deacetylase inhibitors were found to be potent radio-sensitizers of human prostate cancer cells. Radiosensitizing effects of these inhibitors were mediated through cell cycle arrest, down-regulation of anti-apoptotic proteins, up regulation of pro-apoptotic protein (Bax) and abrogation of radiation-induced nuclear translocation of p65
[en] The reduction of the microbial load in the rearing diet of the Ceratitis capitata permit to increase the productivity in pupae. The follow-up of microbial load and physico chemical parameters of differents diets used with several microbial inhibitors. At the time of rearing in scale laboratory has permit to select the diet A and D as being the most favorable. Otherwise, raising semi-massif with the diets A and D confirmed our results and in other parts permit us to value the productivity in pupae of these two diets. The microbiological analysis of the environment, the surfaces, the material and the ingredients permit to determine the sources of diet contamination. The reduction of the microbial load of these sources of contamination and the semi-massif rearing the ceratitis capitata on a rearing diet radiated, permit to get in bigger productivity in pupae. (author). 65 refs
[en] The aim of our study was to evaluate the immediate results and long-term intake of anti-GP IIb / IIIa inhibitors for patients with acute coronary syndrome treated with coronary angioplasty. The use of anti-GP IIb / IIIa is a valid therapeutic option in patients with acute coronary syndrome with signs of severity and for patients undergoing complex angioplasty. Adverse effects of anti-GP IIb / IIIa can be seen to encourage vigilance and careful monitoring during the administration of these molecules and perfect knowledge of their pharmacological properties for appropriate use.
[en] Background and purpose: We have tested the camptothecin analogs, RFS-2000 or CPT-11, in combination with both etoposide and ionizing radiation in vitro to examine the radiation enhancing potential of topoisomerase I plus topoisomerase II (Topo I+Topo II) inhibition in human cancer cells. Materials and methods: H460 human lung carcinoma cells were plated and treated with 10 nM RFS-2000 or 4.5 μM CPT-11 for 4 h. Cells were then irradiated with various doses and treated with 1 μM etoposide for 1.5 h. Cell survival and sublethal damage recovery (SLDR) were determined by clonogenic assay. 7-aminoactinomycin D (7-AAD) staining and flow cytometry were used to analyze cell viability/apoptosis after combined treatment of drugs with radiation. Results: Survival experiments showed radiation dose enhancement ratios (DER) of 1.26, 1.34, and 1.63 for RFS-2000, etoposide, and RFS-2000 plus etoposide, respectively; the corresponding DER values were 1.30, 1.39, and 1.65 for CPT-11, etoposide, and CPT-11 plus etoposide. The analysis of cell viability/apoptosis using 7-AAD staining and flow cytometry showed an additive effect. Greater inhibition of SLDR was observed with RFS-2000 plus etoposide than with either agent separately, but CPT-11 plus etoposide showed a more modest effect upon SLDR. Conclusions: These data show that the combination of Topo I inhibitors, RFS-2000 or CPT-11 plus Topo II inhibitor etoposide, is a more effective radiation enhancer than either agent alone in human lung cancer cells. The mechanism of radiation enhancement may involve inhibition of SLDR with RFS-2000 plus etoposide, but other mechanisms may be involved in the combined treatment including CPT-11