Cyclophosphamide-impaired regulation of hepatic heme metabolism

Summary Im male rats hepatic cytochromes b₅ and P-450 were reduced at different times after treatment with cyclophosphamide (CP) (200 mg/kg i.p. for 3 days). In contrast, microsomal heme did not change until 48 h after the last dose of CP, leading to accumulation of heme in a non-cytochromal form. Parallel to the above changes the heme metabolism showed derangement: -aminolaevulinate synthase, the rate-limiting enzyme in heme synthesis, was depressed and heme oxygenase, the enzyme which catalyzes the oxidative degradation of heme, was increased.     

Ferredoxin reductase catalyzes styrene oxidation to styrene oxide

Summary The flavoprotein ferredoxin reductase catalyzed the oxidation of styrene to styrene oxide in the presence of NADPH. This reaction was inhibited by the addition of catalase and superoxide dismutase. The addition of the nonheme iron protein ferredoxin partially inhibited styrene oxidation. H₂O₂ was also able to catalyze this reaction when added to the enzyme in the absence of NADPH.Acknowledgments. This work was supported by C.N.R. (National Research Council), Rome, Italy contract No. 79.03197.04.     

Non-linear kinetics of microsomal styrene monooxygenase after phenobarbital pre-treatment

Summary Pretreatment of rats with phenobarbital, but not with 3-methylcholanthrene, induces liver microsomal styrene monooxygenase. Under these conditions the kinetic profile is not linear and can be divided into 2 distinct curves. Evidence is presented indicating that the combined treatment with phenobarbital and CoCl₂ destroy the high affinity enzyme, suggesting that the native cytochrome is less sensitive to the action of CoCl₂.This paper was supported by grant No. 181-77-ENVI I awarded by EEC.     

Kinetic behaviour of microsomal styrene monooxygenase and styrene epoxide hydratase in different animal species

Summary The apparent K_m and V_max values of styrene epoxide forming monooxygenase and styrene epoxide hydratase have been evaluated in the liver microsomes of male rats, mice, guinea-pigs and rabbits. Epoxide hydratase gave much higher and more uniform K_m values than the monooxygenase in the species considered.Acknowledgments. This work has been partially supported by the Fondazione Valenti (Milano). To whom enquiries should be addressed.     

Inhibition of liver microsomal epoxide hydrase by cyproheptadine epoxide

Summary Cyproheptadine epoxide is a competitive inhibitor or rat liver microsomal epoxide hydrase with an apparent K₁-value of 0.75 mM. Cyclobenzaprine and its epoxide stimulate in vitro the activity of this enzyme, whereas cyproheptadine, carbamazepine and carbamazepine epoxide have no effect.     

人类与机器感知：交流、相互作用与集成

本书是第六届人类与机器感知国际专题研讨会的论文集，该会议于2004年9月6—9日在意大利的Santa　Caterina　di　Pittinuri举行。这次会议除了8位特邀的讲演者及技术委员会成员之外，参与者人数限制在70人。本书共收集了12个讲座的演讲稿，内容涉及交流、相互作用与集成。对每一个基本主题都有相对应的自然及机器的方法的特邀讲座及技术委员会的讨论，介绍了最新的科技发展水平，概括了公开的问题，并强调了与感知相关的学科之问最佳协同作用，进一步激励了新方法的产生。     

Effect of iron and hemoproteins on hydrogen peroxide-supported styrene oxidation to styrene oxide

Summary Fe²⁺, Fe³⁺ and their complexes with EDTA and hemin, methemalbumin and methemoglobin were active catalyzers of H₂O₂ supported styrene oxidation to styrene oxide. Methemoglobin was the most active compound; its peroxidative activity was comparable to that of cytochrome P-450 in liver microsomes of phenobarbital-treated rats. Cumene hydroperoxide supported styrene oxidation with methemoglobin and microsomal hemoproteins and was found to be more efficient than H₂O₂.This work was supported by C.N.R. (National Research Council) contract No. 79.03197.04.     

Cyclophosphamide-impaired regulation of hepatic heme metabolism

In male rats hepatic cytochromes b5 and P-450 were reduced at different times after treatment with cyclophosphamide (CP) (200 mg/kg i.p. for 3 days). In contrast, microsomal heme did not change until 48 h after the last dose of CP, leading to accumulation of heme in a 'non-cytochromal' form. Parallel to the above changes the heme metabolism showed derangement: delta-aminolaevulinate synthase, the rate-limiting enzyme in heme synthesis, was depressed and heme oxygenase, the enzyme which catalyzes the oxidative degradation of heme, was increased.     

Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis.