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81.
Dr. Sofia Gama Dr. Filipa Mendes Dr. Teresa Esteves Dr. Fernanda Marques Dr. António Matos Dr. José Rino Dr. Joana Coimbra Dr. Mauro Ravera Dr. Elisabetta Gabano Dr. Isabel Santos Dr. António Paulo 《Chembiochem : a European journal of chemical biology》2012,13(16):2352-2362
New [PtCl(pz*NN)]n+ complexes anchored by pyrazolyl‐diamine (pz*NN) ligands incorporating anthracenyl or acridine orange DNA‐binding groups have been synthesized so as to obtain compounds that would display synergistic effects between platination and intercalation of DNA. Study of their interaction with supercoiled DNA indicated that the anthracenyl‐containing complex L2Pt displays a covalent type of binding, whereas the acridine orange counterpart L3Pt shows a combination of intercalative and covalent binding modes with a strong contribution from the former. L2Pt showed a very strong cytotoxic effect on ovarian carcinoma cell lines A2780 and A2780cisR, which are, respectively, sensitive to and resistant to cisplatin. In these cell lines, L2Pt is nine to 27 times more cytotoxic than cisplatin. In the sensitive cell line, L3Pt showed a cytotoxic activity similar to that of cisplatin, but like L2Pt was able significantly to overcome cisplatin cross‐resistance. Cell‐uptake studies showed that L2Pt accumulates preferentially in the cytoplasm, whereas L3Pt reaches the cell nucleus more easily, as clearly visualized by time‐lapse confocal imaging of live A2870 cells. Altogether, these findings seem to indicate that interaction with biological targets other than DNA might be involved in the mechanism of action of L2Pt because this compound, despite having a weaker ability to target the cell nucleus than L3Pt , as well as an inferior DNA affinity, is nevertheless more cytotoxic. Furthermore, ultrastructural studies of A2870 cells exposed to L2Pt and L3Pt revealed that these complexes induce different alterations in cell morphology, thus indicating the involvement of different modes of action in cell death. 相似文献
82.
Esteves AC Monteiro OC Barros-Timmons AM Boemare C Soares MJ Monteiro T Trindade T 《Journal of nanoscience and nanotechnology》2002,2(2):177-181
Hybrid materials consisting of SiO2/CdS particles dispersed in poly(styrene-co-maleic anhydride) and poly(styrene-co-maleimide) have been synthesized and characterized. The polymer nanocomposites were synthesised in situ in the presence of previously prepared inorganic fillers (SiO2/CdS). The nanocomposites were synthesized with the use of as-prepared or surface-modified SiO2/CdS fillers. For both types of nanocomposites, the optical properties were evaluated and the observation of size quantization effects in the optical spectra is discussed. In this context, the influence of the inorganic fillers and polymer matrices on the optical properties of the final nanocomposites was investigated. 相似文献
83.
P. Granger P. Esteves S. Kieger L. Navascues G. Leclercq 《Applied catalysis. B, Environmental》2006,62(3-4):236-243
Abatement processes for the reduction of N2O emissions from acid nitric plants can be implemented in different positions. Among the different possibilities, a catalytic process set up between the ammonia converter and the absorber could be a practicable solution. In those running conditions, at high temperature, in the presence of NO, O2 and water, the catalytic decomposition of N2O (in the absence of a reducing agent) can take place. However, catalysts usually suffer from a strong deactivation owing to the occurrence of thermal sintering which significantly lowers their specific surface area. Catalytic testing performed at laboratory scale showed that zirconia based catalysts stabilised by yttrium incorporation could be of potential interest. However, the mode of yttrium incorporation seems to be a key factor. According to the preparation procedure, surface yttrium enrichment may occur and then strongly inhibit the catalytic decomposition of N2O. Co-precipitation methods can be profitably used for the preparation of modified-ZrO2 catalysts in order to obtain yttrium homogeneously distributed in the bulk material. According to this preparation method, a synergy effect on the catalytic activity and also on the stability has been observed on ZrO2 containing low amount of yttrium whereas an inhibiting effect prevails on highly loaded yttrium based catalysts irrespective of the mode of yttrium incorporation. 相似文献
84.
In the maturation of the Escherichia coli antibiotic Microcin B17, the product of the mcbA gene is modified posttranslationally by the multimeric Microcin synthetase complex (composed of McbB, C, and D) to cyclize four Cys and four Ser residues to four thiazoles and four oxazoles, respectively. The purified synthetase shows an absolute requirement for ATP or GTP in peptide substrate heterocyclization, with GTP one-third as effective as ATP in initial rate studies. The ATPase/GTPase activity of the synthetase complex is conditional in that ADP or GDP formation requires the presence of substrate; noncyclizable versions of McbA bind to synthetase, but do not induce the NTPase activity. The stoichiometry of ATP hydrolysis and heterocycle formation is 5:1 for a substrate that contains two potential sites of modification. However, at high substrate concentrations (>50Km) heterocycle formation is inhibited, while ATPase activity occurs undiminished, consistent with uncoupling of NTP hydrolysis and heterocycle formation at high substrate concentrations. Sequence homology reveals that the McbD subunit has motifs reminiscent of the Walker B box in ATP utilizing enzymes and of motifs found in small G protein GTPases. Mutagenesis of three aspartates to alanine in these motifs (D132, D147, and D199) reduced Microcin B17 production in vivo and heterocycle formation in vitro, suggesting that the 45 kDa McbD has a regulated ATPase/GTPase domain in its N-terminal region necessary for peptide heterocyclization. 相似文献
85.
RD Barr T Simpson CE Webber GJ Gill J Hay M Eves AC Whitton 《Canadian Metallurgical Quarterly》1998,34(6):873-877
Mature and post-translational precursor gastrin forms are growth factors for colorectal tumours. The immunogen Gastrimmune is composed of the amino terminus of gastrin-17 linked to diphtheria toxoid and raises antibodies in situ which neutralise amidated and glycine-extended gastrin-17. The aim of the study was to determine the effect of treatment with 5-fluorouracil(5-FU)/leucovorin on the antibody titres induced by Gastrimmune and the effect of combination therapy on the growth of the rat colon tumour DHDK12. Gastrimmune was administered to rats s.c. at 3 weekly intervals. The rat colon tumour line DHDK12 was injected into the abdominal wall of BDIX rats. Combinations of 5-FU/leucovorin were injected i.v. on days 1, 3 and 5, with the cycle repeated every 4 weeks. Antibody titres were measured by an ELISA technique. Antibody titres were followed for 40 weeks after Gastrimmune (500 microg.ml(-1)) immunization, with titres peaking between 10 and 20 weeks after a single immunisation and falling by week 30. At termination, no effect was observed on either the histological appearance of the gastro-intestinal tract or the proliferation of the colonic mucosa. Pre- and post-treatment with 5-FU/leucovorin (30 mg.kg(-1)) had no effect on the kinetics and level of antibody response to Gastrimmune. Gastrimmune (200 microg.ml(-1)) and 5-FU/leucovorin combinations (12.5 and 20 mg.kg(-1)) increased the therapeutic effects on the in vivo growth of DHDK12 tumors when compared to the agents given singly. Gastrimmune immunisation may be a therapeutic option for the treatment of colorectal cancer in combination with 5-FU/leucovorin. 相似文献
86.
We studied the effect of transpupillary thermotherapy (TTT) by a diode laser at 810 nm combined with episcleral ruthenium-106 plaque treatment (106Ru) on lens transparency in patients with choroidal melanoma. Lens transmission of blue-green light was measured by fluorophotometry in 17 patients treated with 106Ru treatment and TTT (measured 0.36 years after treatment), 12 patients treated with 106Ru alone (measured 19 years after treatment) and 25 age-matched healthy controls. Differences in lens transmission were not significant between treated and untreated fellow eyes (p > 0.15) nor between patient and control eyes (p > 0.25). TTT of choroidal melanoma combined with 106Ru plaque irradiation did not have a significant effect on the lens transparency up to 6 years after treatment. 相似文献
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90.
The apparent preservation of word priming effects in amnesia has been interpreted as supporting the view that implicit memory depends on brain systems that are independent of mesial temporal lobe structures which are in part responsible for explicit memory disorders. Nevertheless, a number of studies have demonstrated word priming deficits in amnesic patients relatively to normal subjects, suggesting that such structures may also be involved in implicit memory. To determine whether one such structure, the hippocampal formation, is a component of the brain system subserving word priming, a 3-D PET study was carried out in 13 normal individuals. Encoding was carried out using the brief multiple presentation technique, a procedure that allows one to effectively circumvent contamination of implicit memory tasks by explicit memory strategies. Results revealed that word priming was indeed associated with an activation of the right hippocampal formation. This finding of an hippocampal involvement in word priming calls into question the notion of absolute dissociability between the brain systems underlying performance on various explicit and implicit memory tasks. 相似文献