Glucuronidation of N-hydroxy heterocyclic amines by human and rat liver microsomes

The food-borne carcinogenic and mutagenic heterocyclic aromatic amines undergo bioactivation to the corresponding N-hydroxy (OH)-arylamines and the subsequent N-glucuronidation of these metabolites is regarded as an important detoxification reaction. In this study, the rates of glucuronidation for the N-OH derivatives of 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), 2-amino-6-methyl-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) by liver microsomal glucuronosyltransferase were compared to that of the proximate human urinary bladder carcinogen, N-OH-aminobiphenyl (N-OH-ABP) and the proximate rat colon carcinogen N-OH-3,2'-dimethyl-4-amino-biphenyl (N-OH-DMABP). Human liver microsomes catalyzed the uridine 5'-diphosphoglucuronic acid (UDPGA)-dependent glucuroidation of N-OH-IQ, N-OH-PhIP, N-OH-Glu-P-1 and N-OH-MeIQx at rates of 59%, 42%, 35% and 27%, respectively, of that measured for N-OH-ABP (11.5 nmol/min/mg). Rat liver microsomes also catalyzed the UDPGA-dependent glucuronidation of N-OH-PhIP, N-OH-Glu-P-1 and N-OH-IQ at rates of 30%, 20% and 10%, respectively of that measured for N-OH-DMABP (11.2 nmol/min/mg); activity towards N-OH-MeIQx was not detected. Two glucuronide(s) of N-OH-PhIP, designated I and II, were separated by HPLC. Conjugate II was found to be chromatographically and spectrally identical with a previously reported major biliary metabolite of PhIP in the rat, while conjugate I was identical with a major urinary metabolite of PhIP in the dog. Hepatic microsomes from rat, dog and human were found to catalyze the formation of both conjugates. The rat preferentially formed conjugate II (I to II ratio of 1:15), while the dog and human formed higher relative amounts of conjugate I (I to II ratio of 2.5:1.0 and 1.3:1.0 respectively). Fast atom bombardment mass spectrometry of conjugates I and II gave the corresponding molecular ions and showed nearly identical primary spectra. However, collision-induced spectra were distinct and were consistent with the identity of conjugates I and II as structural isomers. Moreover, the UV spectrum of conjugate I exhibited a lambda max at 317 nm and was essentially identical to that of N-OH-PhIP, while conjugate II was markedly different with a lambda max of 331 nm. Both conjugates were stable in 0.1 N HCl and were resistant to hydrolysis by rat, dog and human liver microsomal beta-glucuronidases.(ABSTRACT TRUNCATED AT 400 WORDS)     

筛查基因突变的新技术——循环双脱氧指纹图谱法及其应用

建立了适用于大批量标本基因突变筛查的双脱氧指纹图谱法即ｄｄＦ。该技术民测定ＤＮＡ序列的双脱氧末端终止法及ＳＳＣＰ二者长处于一身，即只作一个双脱氧末端终止反应，然后将反应产物在与ＳＳＣＰ相同的电泳条件下进行聚丙烯酰胺凝胶电泳，这样有突变的样品不会漏检，阳性检出率高达１００％。     

Protein adsorption onto poly(ether urethane ureas) containing Methacrol 2138F: a surface-active amphiphilic additive

Surface characterization and protein adsorption studies were carried out on a series of additive dispersed and additive coated poly(ether urethane ureas), PEUUs, to characterize early events in the blood compatibility of these materials. A hypothesis that is based on surface hydrophilicity, surface flexibility, and adsorption media has been developed to understand the modulated adsorption of plasma proteins by PEUU additives. Electron spectroscopy for chemical analysis (ESCA) and contact angle analysis were performed on two PEUU formulation as well as on PEUU formulations modified with Methacrol 2138F (co[diisopropylaminoethyl methacrylate (DIPAM)/decyl methacrylate (DM)][3/1]) or acrylate or methacrylate polymer or copolymer analogs of Methacrol 2138F. Methacrol 2138F is a commercially used amphiphilic copolymethacrylate. ESCA showed that the PEUUs loaded with Methacrol 2138F or with its hydrophilic component, homopoly (DIPAM) (h-(DIPAM)), had a higher percentage of nitrogen at their surfaces than did the base PEUUs. Contact angle analysis also showed that the air side of PEUU formulations loaded with Methacrol 2138F were more hydrophobic than was the air side of base PEUUs when films were cast from dimethylacetamide. However, during contact angle testing, the air side of PEUU films loaded with Methacrol 2138F rapidly became more hydrophilic than did the air side of the base PEUU films. A radioimmunoassay and whole or diluted human plasma were also used to characterize the presence of the proteins fibrinogen, immunoglobulin G, factor VIII/von Willebrand factor, Hageman factor (factor XII), and albumin, on the surface of the same PEUUs as analyzed by ESCA and contact angle. The protein adsorption assay showed that PEUU films loaded or coated with Methacrol 2138F, with a copolyacrylate analog of Methacrol 2138F (co(diisopropylaminoethyl acrylate [DIPAA]/decyl acrylate [DA]) [3/1]), or with the hydrophilic polyacrylate or polymethacrylate component analogs of Methacrol 2138F (h-DIPAM or h-DIPAA) adsorbed significantly lower amounts of the proteins than did either the base PEUU formulations or the homopoly(decyl methacrylate) (h-DM) or homopoly(decyl acrylate) (h-DA) coated or loaded PEUUs.     

Measuring health-related quality of life in rheumatoid arthritis: validity, responsiveness and reliability of EuroQol (EQ-5D)

The efficacy of photodynamic therapy is dependent upon the optical dose rate or upon the fractionation schedule on the light. These effects are thought to be limited by the time required for oxygen diffusion from the capillaries, since this therapy can consume oxygen faster than it can be supplied to tissues distant from the blood vessels. Oxygen diffusion and consumption by metabolic and photochemical mechanisms have been modeled here to compare theoretical predictions with experimental results of varying light fractionations and delivered dose rates. The mathematics of the problem have been described in the literature, and the present study extends these calculations to allow a more direct and quantitative comparison with fractionation experiments, using both analytical and numerical arguments. The optimum fraction time was found to depend only on the intercapillary spacing and not on the intensity of irradiation or the concentration of photosensitizer. The calculations indicate that experimentally observed optimum fractionation times of 30 and 60 s correspond to a distance from capillary to cell of approximately 1 mm. These results suggest that the fractionated light irradiation experiments need careful interpretation, and some possible reasons for longer optimum fractionation times are discussed.     

Rapid synthesis of La0.7Sr0.3MnO3+λ catalysts by microwave irradiation process

Microwave irradiation processing (MIP) was considered as a potential method to synthesize perovskite-type oxides rapidly, cleanly and energy-efficiently. In this paper, La_0.7Sr_0.3MnO_3+λ, a kind of promising catalyst for automobile exhaust purification, was successfully prepared by MIP in not more than 5 min. The sol–gel method was also used for comparison. All the samples were evaluated by catalytic activity tests in the simulated exhaust and characterized by XRD, BET, TEM and XRF analyses. The results showed that the integrated perovskite-type phase and uniform particle size were obtained in the microwave-treated samples. And those ones exhibited a better oxidation activity under slightly oxygen-rich condition than that by sol–gel method, which may be related to more A-site cation vacancies and larger bulk oxygen content generated in MIP. Possible formation mechanism of perovskites in MIP was also discussed.     

A Linear Phase Condition for Volterra Filters

In linear finite-impulse-response filter design, it is desirable that the filter frequency response has linear phase (LP). In this brief, we investigate the LP concept for nonlinear Volterra filters. The LP condition of Volterra filters is defined in terms of its output spectrum in which the phase term introduced by the Volterra kernels is linear. It is shown that under certain symmetry conditions, the LP condition is satisfied by Volterra filters. Moreover, the LP condition for Volterra filters can be considered as an extension to the linear filter case.     

Characterizing the deformation behavior of Tertiary sandstones

Tertiary sandstones possess deformational behavior different from hard rocks, especially the relatively larger amount of volumetric dilation during shearing. Such excess dilation contributes to the increase of crown settlement during tunnel excavation and accounts for several cases of tunnel squeezing within Tertiary sandstones. Therefore, the deformation behavior of Tertiary sandstones sampled from more than 13 formations was studied. To distinguish the volumetric deformation induced by hydrostatic stress or by shear stress as well as to decompose the elastic and the plastic components of strains, special experimental techniques, including pure shear tests and cycles of loading–unloading were applied.The experimental results reveal that the deformation of Tertiary sandstone exhibits the following characteristics: (1) significant amount of shear dilation, especially elastic shear dilation; (2) non-linear elastic and plastic deformation; (3) plastic deformation occurs prior to the failure state. Furthermore, features of plastic deformation were inferred from experimental results and, as a result, the geometry of plastic potential surface and the hardening rule were accordingly determined. A constitutive model, involving nonlinear elastic/plastic deformation and volumetric deformation induced by shear stress, is proposed. This proposed model simulates the deformational behavior for the shear-dilation-typed rocks reasonably well. Furthermore, tests on the versatility of the proposed model, including varying hydrostatic stress and stress paths, indicate that the proposed model is capable of predicting deformational behavior for various conditions.     

陆丰城区旧城改造探析

城市建设反映地方的社会、经济发展水平，因为各种各样的原因，陆丰市（指城区，下同）新区开发缓慢，旧城老化严重，城市建设水平明显落后于周边其他县市。为了改善人居环境，提高城市建设水平，加快城市建设步伐，政府制定了一系列方针政策，旧城改造作为人民群众迫切需要和城市建设的重要任务已经提到政府的工作日程上，因此探析陆丰市旧城状况和改造思路具有重要的现实意义。