Marmoset cytochrome P450 2B6, a propofol hydroxylase expressed in liver

1. The common marmoset (Callithrix jacchus) is a useful experimental animal to evaluate the pharmacokinetics of drug candidates. Cytochrome P450 (P450) 2B enzyme in marmoset livers has been identified; however, only limited information on the enzymatic properties and distribution has been available.

2. Marmoset P450 2B6 amino acids showed high sequence identities (>86%) with those of primates including humans and cynomolgus monkeys. Phylogenetic analysis using amino acid sequences indicated that marmoset P450 2B6 was closer to human and cynomolgus monkey P450 2B6 than to P450 2B orthologs of other species, including pigs, dogs, rabbits and rodents.

3. Quantitative polymerase chain reaction analysis using specific primers showed P450 2B6 mRNA predominantly expressed in livers among the five marmoset tissues, similar to those of humans and cynomolgus monkeys.

4. Marmoset P450 2B6 heterologously expressed in Escherichia coli membranes oxidized 7-ethoxycoumarin, pentoxyresorufin, propofol and testosterone, at roughly similar rates to those of humans and/or cynomolgus monkeys. A high capacity of marmoset P450 2B6 with propofol 4-hydroxylation (at low ionic strength conditions) with a low K_m value was relatively comparable to that for marmoset livers.

5. These results collectively indicated a high propofol 4-hydroxylation activity of P450 2B6 expressed in marmoset livers.

     

A reaction route graph analysis of the electrochemical hydrogen oxidation and evolution reactions

The reaction route (RR) graph approach recently developed by us for complex, non-linear kinetic mechanisms is applied to the hydrogen oxidation and evolution reactions. A corresponding RR graph is constructed and translated into an equivalent electrical circuit network by associating each elementary step with a characteristic resistance for the steady-state case and considering the overall reaction as a power source. It is further shown that the steady-state kinetics of the reaction can be investigated employing the conventional methods of the electrical network theory. Using a set of rate constants for the hydrogen evolution reaction (her) in alkaline solutions from the literature, the dominant RRs are identified and simplified mechanisms and kinetics derived.     

ALTERED HEPATIC METABOLISM OF FATTY ACIDS IN RATS FED A HYPOLIPIDAEMIC DRUG, FENOFIBRATE

The aim of this study was to examine the effects of dietary fenofibrate (0.05% in the diet) on ketone body production and lipid secretion in isolated perfused rat liver. Feeding with fenofibrate for 7–9 days caused an increased liver weight. Ketone body production was significantly greater in the livers perfused with oleic acid than in those perfused without fatty acid, with the elevation of the ratio ofβ-hydroxybutyrate:acetoacetate indicating an increased redox potential in mitochondrial compartments by exogenous fatty acid. On the other hand, fenofibrate feeding caused a further stimulation of ketone body production from both endogenous and exogenous fatty acid substrates, respectively, with a decreased ratio ofβ-hydroxybutyrate:acetoacetate as compared to respective control livers, indicating a decreased redox potential. Hepatic secretion of triglyceride, but not of cholesterol, was decreased markedly in the fenofibrate-fed rats, especially when oleate was provided, suggesting an inverse relationship between rates of ketogenesis and triglyceride secretion. These results suggest that the altered hepatic metabolism of long-chain fatty acids between oxidation and esterification caused by fenofibrate may thus be a factor responsible for the decreased secretion of triglyceride, hence leading to hypotriglyceridaemiain vivo.     

Exercise metabolism during 1 hour of treadmill walking while taking high and low doses of propranolol,metoprolol, or placebo

Aerobic exercise and beta-blocking drugs are regularly prescribed as treatment for hypertension and as a prophylactic for patients at risk from coronary heart disease and for those recovering from an infarct. Some beta blockers, particularly non-beta₁-selective drugs, may make exercise more difficult, possibly by interfering with substrate metabolism during exercise. This study examined the effects of low and high doses of a beta₁-selective blocker, metoprolol, and a nonselective beta blocker, propranolol, on exercise metabolism. The study involved 20 healthy subjects (10 men, 10 women) who walked on a treadmill at 50% of their maximal oxygen uptake for 1 h on five occasions, separated by 7 days. On each of the five occasions they received one of the following treatments, given in random order: placebo, metoprolol 50 mg, metoprolol 100 mg, propranolol 40 mg, or propranolol 80 mg, all taken twice daily. Fat oxidation, expressed as a percentage of total energy expenditure, was significantly lower than with placebo for all of the active treatments except metoprolol 50 mg (placebo: 42.7 ± 11.6%; metoprolol 50 mg: 38.7 ± 14.1%, p = NS; metoprolol 100 mg: 36.3 ± 13.7%, p = 0.05; propranolol 40 mg: 31.2 ± 9.3%, p = 0.01; propranolol 80 mg: 29.5 ± 10.9%, p = 0.01); and significantly lower with propranolol than with metoprolol (propranolol 40 mg: p = 0.0036; propranolol 80 mg: p = 0.01). Plasma ammonia concentration was significantly higher than with placebo with propranolol 40 mg, propranolol 80 mg, and metoprolol 100 mg (p = 0.01 for all); with metoprolol 50 mg, there was no difference from placebo (p = NS). Both beta blockers in this study reduced fat metabolism and increased perceived exertion to some degree. Additional inhibition of fat oxidation occurred with the nonselective drug, probably in intramuscular rather than adipose lipolysis, and was probably beta₂ mediated. The results of this study suggest that a selective beta blocker has less of an adverse effect on substrate metabolism than does a nonselective beta blocker. Beta₁-selective drugs may offer advantages in patients who undertake regular aerobic exercise.     

Influence of Chemical Oxygen Demand Concentrations on Anaerobic Ammonium Oxidation by Granular Sludge From EGSB Reactor

INTRODUCTION The phenomenon of anaerobic ammonium oxidation was originally discovered in a denitrifying fluidized-bed reactor treating effluent from a methanogenic reactor in the 1990s[1]. Anaerobic ammonium oxidation (ANAMMOX) process is a strictly anaerobic denitrification process, in which ANAMMOX autotrophic bacteria directly oxidize ammonium to dinitrogen gas using nitrite as electron acceptor. In recent years, the anammox process has received great attention and lots of researc…     

超细α-FeOOH制备过程研究 Ⅰ.制备工艺

以制备晶形、粒度、轴比等满足高性能磁粉要求的铁黄为目标,研究了碱法超细α-FeOOH合成的工艺配方和工艺条件对粒子性能的影响,包括碱比、气量、转速、Fe(OH)_2结晶条件、熟化时间等工艺参数的影响规律。重复稳定地制备出三类超微粒α-FeOOH粒子,其粒度分别为0.18、0.28、0.39μm,分布均匀,无枝叉。     

Spectroelectrochemical studies of tetrasulfonated metallophthalocyanines adsorbed on the basal plane of graphite in the presence of cysteine

Cobalt and iron tetrasulfonated phthalocyanines (M-TSPc) have been studied by electroreflectance spectroscopy in the adsorbed state on the basal plane of HOPG in a borate buffer (pH 9). Since both complexes exhibit electrocatalytic activity for the electro-oxidation of cysteine, we looked at the changes of the visible spectra of the adsorbed complexes upon adding millimolar amounts of cysteine to the electrolyte. Under zero-current conditions (open circuit) the addition of cysteine causes large changes in the reflectance spectra of both Co-TSPc and Fe-TSPc. In the case of Co-TSPc the spectra resemble that of Co(I)TSPc whereas for Fe-TSPc bands at 424 and 626 nm are observed. The open circuit potential shifts to values close to the standard potential of the M(II)/M(I) couple. We attribute these changes, particularly in the case of Fe-TSPc, to the formation of a radical adduct between the adsorbed phthalocyanine and the cysteine molecule, with partial electron-transfer from the cysteine to the metal center. Evidences for these adducts is not found when polarizing the electrode, which shows that they behave as very unstable intermediates in the catalytic process.     

Ⅴ-Ti催化剂低氧催化氧化邻二甲苯制苯酐——Ⅱ.TiO_2晶体结构及助剂作用的影响

研究了V-Ti体系中TiO_2晶体结构与催化活性的联系,本系统中,当焙烧温度超过650℃,由于TiO_2由锐钛矿型转变为金红石型,使催化活性降低。助剂作用的ESCA、XRD、LRS研究表明,与通常V-Ti系催化剂不同,本催化剂由于助剂的作用,使V=O键减弱而利于活化;且随K助剂含量增加,V_2O_(4.33)晶胞的001面取向优化加强,更宜于催化活性的充分显示。     

Electrochemical investigation of formic acid electro-oxidation and its crossover through a Nafion® membrane

This work studies formic acid as an anode fuel for polymer electrolyte fuel cells and investigates the electro-oxidation of formic acid on Pt/C. Fuel crossovers through the Nafion^® 115 membrane at different temperatures and concentrations are reported. A linear dependence of the crossover current on the temperature and concentration is obtained. It is found that the crossover can be reduced by five times and a higher performance can be rendered by formic acid when compared to methanol under the same conditions. Electrochemical impedance measurements are conducted to interpret the reaction mechanism of formic acid oxidation. The effect of the electrode potential on the impedance pattern is revealed and an impedance model incorporating the reaction kinetics information is developed to simulate the experimental impedance response.