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281.
Amtul Z Rasheed M Choudhary MI Supino R Khan KM Atta-Ur-Rahman Rosanna S 《Biochemical and biophysical research communications》2004,319(3):1053-1063
Based on structure of the substrate of urease and for the purpose of designing pharmacophore models for urease inhibitors, which could be effective in physiological and pharmacological studies, a series of twenty-five 1,3,4-diazole-2(3H)-thiones-2(3H)-thiones, 1,3,4-diazoles-2(3H)-thiones, and 1,2,4-tri-3-thiones (OSNs) were designed, synthesized, and evaluated for various kinetic parameters of urease inhibition. OSNs inhibited the activity of urease(s) in a concentration dependent fashion. Dixon as well as Lineweaver-Burk plots and their secondary replots indicated that the nature of inhibition was of pure competitive type for all the 25 compounds. 5-[4-(hydroxy)phenyl]-1,3,4-thiadiazole-2(3H)-thione was found to be the most active one with a Ki value of 2 microM. The Ki values were increased with an increase in substrate concentrations. Apparently, OSNs employ a homologous mechanism of action by exploiting a common transition catalysis state and acting as ligand chelators to form octahedral complexes with the urease enzymes in an orientation-specific mode. The inhibition was slightly potentiated by lower pH and not abolished in the presence of NH2OH (a scavenger of histidine residue). Because of their safe profile in the genotoxic assay, they may be pursued in the near future for human testing 相似文献
282.
Sticchi E Fatini C Gensini F Battaglini B Liotta AA Abbate R 《Biochemical genetics》2004,42(3-4):121-127
In endothelial cells nitric oxide (NO) is synthesized by endothelial-nitric oxide synthase (e-NOS), constitutively expressed and encoded by a 26-exon gene, located on chromosome 7q35-36. The prevalence of the T rare variant of the G894T polymorphism in exon 7 of the e-NOS gene (Glu-->Asp amino acid substitution) has been reported to be significantly higher in patients with coronary spasm and coronary artery disease. To date G894T polymorphism detection is performed by PCR-RFLP assay. In order to establish a high-speed genotyping method, we have taken advantage of the Light Cycler instrument, a thermal cycler that combines rapid-cycle DNA amplification with a real-time fluorescence monitoring. This technology is based on hybridization of the adjacent fluorescently labeled probes with PCR products. This methodology is considered more accurate and less time-consuming than conventional PCR-RFLP assay. To validate this technique we genotyped 270 healthy subjects. The results were consistent with those obtained from PCR-RFLP assay. 相似文献
283.
Marzocco S Di Paola R Genovese T Sorrentino R Britti D Scollo G Pinto A Cuzzocrea S Autore G 《Life sciences》2004,75(12):1417-1433
In the present study we evaluate the effect of methylguanidine (MG), a product of protein catabolism, in a model of acute inflammation (zymosan induced inflammation) in mice where oxyradical and nitric oxide (NO) play a crucial role. Our data show that MG, given intraperitoneally at the dose of 30 mg/Kg, inhibits the inflammatory response reducing significantly (P < 0.05) peritoneal exudates formation, mononuclear cell infiltration and histological injury in mice. Furthermore, our data suggests that there is a significant (P < 0.05) reduction in kidney, liver and pancreas injury as demonstrated by the reduction in amylase, lipase, creatinine, AST, ALT, bilirubine and alkaline phosfatase levels. MG is also able to reduce the appearance of nitrotyrosine and of the nuclear enzyme poly (adenosine diphosphate [ADP]-ribose) synthase (PARS) immunoreactivity in the inflamed intestinal and lung tissues. The histological examination revealed a significant reduction in zymosan-induced intestinal and lung damage in MG-treated mice. Taken together, the present results demonstrate that MG exerts potent anti-inflammatory effects on zymosan-induced shock. 相似文献
284.
Research on reproductive isolation in African cichlid fishes has largely focused on the role of nuptial colours, but other sensory modes may play an important role in mate choice. Here, we compare the relative importance of visual and olfactory cues in mate recognition by females of a Lake Malawi cichlid species. Female Pseudotropheus emmiltos were given a choice of spawning next to a conspecific male or a male of the closely-related sympatric Pseudotropheus fainzilberi. Significant preference for conspecific males only occurred when olfactory cues were present. This suggests that divergence of olfactory signals may have been an important influence on the explosive radiation of the East African species flock. 相似文献
285.
Rosanna Caliandro Alessandro Pesaresi Luca Cariati Antonio Procopio Manuela Oliverio 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):794-803
Acetylcholinesterase inhibitors were introduced for the symptomatic treatment of Alzheimer’s disease (AD). Among the currently approved inhibitors, donepezil (DNP) is one of the most preferred choices in AD therapy. The X-ray crystal structures of Torpedo californica AChE in complex with two novel rigid DNP-like analogs, compounds 1 and 2, have been determined. Kinetic studies indicated that compounds 1 and 2 show a mixed-type inhibition against TcAChE, with Ki values of 11.12?±?2.88 and 29.86?±?1.12?nM, respectively. The DNP rigidification results in a likely entropy-enthalpy compensation with solvation effects contributing primarily to AChE binding affinity. Molecular docking evidenced the molecular basis for the binding of compounds 1 and 2 to the active site of β-secretase-1. Overall, these simplified DNP derivatives may represent new structural templates for the design of lead compounds for a more effective therapeutic strategy against AD by foreseeing a dual AChE and BACE-1 inhibitory activity. 相似文献
286.
Comparative studies on functional and secretory properties of macrophage cell lines derived from different anatomical sites 总被引:2,自引:0,他引:2
Elisabetta Blasi Manuela Puliti Lucia Pitzurra Roberta Barluzzi Rosanna Mazzolla Cecilia Adami George W. Cox Francesco Bistoni 《FEMS immunology and medical microbiology》1994,9(3):207-215
Abstract In the present study, we compared four macrophage (Mφ) cell lines from different anatomical origins for functional and secretory activities against the two morphogenetic forms of the fungus Candida albicans . We show that all the cell lines actively phagocytize the yeast and exert antimicrobial activity against both forms o3 Candida , although Mφ of microglial origin are the most effective. When assessed for secretory properties, microglial Mφ exhibit a peculiar patten with respect to other Mφ populations under either basal or stimulated conditions. In particular, only microglial Mφ fail to respond to the hyphal form of the fungus (H- Candida ), which instead acts as a potent tumor necrosis factor inducer in the other Mφ cell lines. When exposed to H- Candida , microglial Mφ are indistinguishable from other Mφ in their ability to modulate specific surface adhesion molecules. In addition to strengthening the knowledge on functional heterogeneity among Mφ, our data provide evidence on the peculiar behavior of microglial Mφ. To what extent Mφ heterogeneity may be related to tissue homeostasis is discussed. 相似文献
287.
Rosanna Di Paola Emanuela Mazzon Carmelo Muià Concetta Crisafulli Tiziana Genovese Paolo Di Bella Emanuela Esposito Marta Menegazzi Rosaria Meli Hisanori Suzuki Salvatore Cuzzocrea 《Nitric oxide》2007,16(1):118-130
Hypericum perforatum is a medicinal plant species containing many polyphenolic compounds, namely flavonoids and phenolic acids. Since polyphenolic compounds have high antioxidant potential, we have investigated the effects of H. perforatum extract on the development of multiple organ dysfunction syndrome caused by zymosan (500 mg/kg, administered i.p. as a suspension in saline) in mice. Organ failure and systemic inflammation in rats was assessed 18 h after administration of zymosan and/or H. perforatum extract and monitored for 12 days (for loss of body weight and mortality). Treatment of mice with H. perforatum extract (30 mg/kg i.p., 1 and 6h after zymosan) attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan, pulmonary, intestinal and pancreatic injury, and renal dysfunction as well as the increase in myeloperoxidase in the lung and intestine. Immunohistochemical analysis for inducible nitric oxide synthase (iNOS), nitrotyrosine, and poly(ADP-ribose) (PAR) revealed positive staining in lung and intestine tissues obtained from zymosan-injected mice. The degree of staining for nitrotyrosine, iNOS, and PAR was markedly reduced in tissue sections obtained from zymosan-treated mice, which received H. perforatum extract. In conclusion, this study provides evidence, for the first time, that H. perforatum extract attenuates the degree of zymosan-induced multiple organ dysfunction syndrome in mice. 相似文献
288.
Summary Dynamic modeling of ecological phenomena has been greatly facilitated by the recent development of continuous system simulator programs. This paper illustrates the application of one of these programs, S/360 Continuous System Modeling Program (S/360 CSMP), to four systems of graduated complexity. The first is a two species system, with one feeding on the other, using differential equations with constant coefficients. The second and third systems involve two competing plant species in which the coefficients of the differential equations are varying with time. The final example considers the management of a postulated buffalo herd in which the dynamics of the herd population and composition by sex and age is combined with various strategies to control its size and to optimize buffalo production. 相似文献
289.
290.