Changes in serum lipoprotein (a) levels related to hyperlipidemia during pregnancy--comparing normal pregnancy and toxemia of pregnancy

The aim of this 2-year study funded by the English National Board for Nursing, Midwifery and Health Visiting was to examine the relationship between teaching, support, supervision and role modelling in student clinical learning within the context of Project 2000 courses. The research, using a two-stage case-study design, employing predominantly qualitative methods of data collection, investigated the perceptions of students, tutors and practitioners of their experiences of these processes in the clinical setting. This paper focuses on the findings obtained from the practitioner data, high-lighting not only the significant role played by practitioners in facilitating student learning, but also the implications for practitioners in undertaking this role. The preparation required for supervising clinical learning, the integration of theory and practice and the organization of patient care have been identified as particularly important to the development of effective clinical learning environments.     

Optimal household refrigerator replacement policy for life cycle energy,greenhouse gas emissions,and cost

Although the last decade witnessed dramatic progress in refrigerator efficiencies, inefficient, outdated refrigerators are still in operation, sometimes consuming more than twice as much electricity per year compared with modern, efficient models. Replacing old refrigerators before their designed lifetime could be a useful policy to conserve electric energy and greenhouse gas emissions. However, from a life cycle perspective, product replacement decisions also induce additional economic and environmental burdens associated with disposal of old models and production of new models. This paper discusses optimal lifetimes of mid-sized refrigerator models in the US, using a life cycle optimization model based on dynamic programming. Model runs were conducted to find optimal lifetimes that minimize energy, global warming potential (GWP), and cost objectives over a time horizon between 1985 and 2020. The baseline results show that depending on model years, optimal lifetimes range 2–7 years for the energy objective, and 2–11 years for the GWP objective. On the other hand, an 18-year of lifetime minimizes the economic cost incurred during the time horizon. Model runs with a time horizon between 2004 and 2020 show that current owners should replace refrigerators that consume more than 1000 kWh/year of electricity (typical mid-sized 1994 models and older) as an efficient strategy from both cost and energy perspectives.     

The leaching of sintered CuS disks with ferric chlorides

A comparative study of chemical and electrochemical leaching of a sintered disk of CuS was carried out at 343 to elucidate the leaching mechanism of CuS with FeCl₃. The leaching,rate of CuS exhibited a half order dependence on the FeCl₃ concentration, but the addition of FeCl₂ slightly reduced the leaching rate. The mixed potential of CuS exhibited a 53 mV decade^-1 dependence upon the FeCl₃ concentration; no significant effect on the mixed potential was observed by the addition of FeCl₂. Based on these observations, an electrochemical mechanism is proposed which involves the oxidation of CuS and the reduction of FeCl₂ ⁺ . The activation energy in chemical leaching of CuS was 46.7 kJ mol^-1, while in electrochemical leaching, it was 50.4 kJ mol^-1. By converting the leaching rate to electric current density,i, a 110 mV decade^-1 dependence of mixed potential, E, against log i is obtained. This dependence of the mixed potential during chemical leaching of CuS on FeCl₃ concentration agrees with the value theoretically expected from the electrochemical model of the leaching process. These findings strongly support an electrochemical mechanism for the FeCl₃ leaching of CuS. HIROSHI HIAI, formerly Graduate Student with Kyoto University     

Purification and characterization of rhesus monkey liver amido hydrolases and their roles in the metabolic polymorphism for E6123, a platelet-activating factor receptor antagonist

We previously showed that a polymorphism for E6123 [(S)-(+)-6- (2-chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5- tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a] [1,4]diazepine] metabolism exists only in rhesus monkeys. In the present study, we purified, from rhesus monkey hepatic microsomes, three amido hydrolases that are involved in the metabolic polymorphism. Two forms of amido hydrolase from an extensive metabolizer and one from a poor metabolizer were purified by Q-Sepharose Fast Flow, Red A-agarose, octylamino-Sepharose 4B, and hydroxyapatite-Ultrogel chromatography, after solubilization with Lubrol. The three purified enzymes had the same molecular mass (47 kDa), and their amino-terminal amino acid sequences were identical. The enzymes were different from various known carboxylesterases in terms of substrate specificity, molecular mass, and amino-terminal amino acid sequence. They resembled arylacetamide deacetylase from human hepatic microsomes with respect to molecular mass and amino-terminal amino acid sequence. The KM values of the high and low affinity enzymes in the extensive metabolizer and the sole enzyme in the poor metabolizer were 37.6, 73.0, and 76.5 microM, respectively. The Vmax values were 3312.4, 504.8, and 427.9 pmol/min/mg of protein, respectively. The high affinity enzyme in extensive metabolizer appears to be quite distinct, whereas the low affinity enzyme in extensive metabolizer in similar or identical to the sole enzyme in poor metabolizer. Thus, the metabolic polymorphism in rhesus monkey may depend upon the existence of the high affinity enzyme in extensive metabolizer.     

Spontaneous chemiluminescence production, lipid peroxidation, and covalent binding in rat hepatocytes exposed to acetaminophen

Spontaneous chemiluminescence associated with the cell injury was observed in the isolated rat hepatocyte suspension during acetaminophen (APAP) metabolism, indicating the occurrence of oxidative stress. APAP apparently affected the hepatocytes in various manners. APAP, at low concentrations (1-2 mM), damaged the hepatocytes due to lipid peroxidation provoked during APAP metabolism, while at high concentrations (5-50 mM), APAP protected the hepatocytes due to a chemical antioxidant effect of the unmetabolized APAP that remained in the medium because of the saturation of APAP metabolism. The covalent binding of APAP to the hepatocytes increased with APAP concentration up to 50 mM without loss of cell viability. When an overdose of APAP was administered to rats, the APAP plasma concentration was around 1-3 mM, which corresponded to the concentration range where lipid peroxidation occurred in the isolated hepatocytes. Thus, it seems likely that lipid peroxidation contributes to the APAP-induced hepatotoxicity in the early stage of the toxic process.     

Regioselectivity and substrate concentration-dependency of involvement of the CYP2D subfamily in oxidative metabolism of amitriptyline and nortriptyline in rat liver microsomes

Kinetic analysis of the metabolism of amitriptyline and nortriptyline using liver microsomes from Wister rats showed that more than one enzyme was involved in each reaction except for monophasic amitriptyline N-demethylation. The Vmax values particularly in the high-affinity sites for E-10-hydroxylation of both drugs were larger than those for Z-10-hydroxylations. Their E- and E-10-hydroxylase activities in Dark-Agouti rats, which are deficient for CYP2D1, were significantly lower than those in Wistar rats at a lower substrate concentration (5 microM). The strain difference was reduced at a higher substrate concentration (500 microM). A similar but a smaller strain difference was also observed in nortriptyline N-demethylase activity, and a pronounced sex difference (male > female) was observed in N-demethylation of both drugs in Wistar and Dark-Agouti rats. The reactions with the strain difference were inhibited concentration-dependently by sparteine, a substrate of the CYP2D subfamily, and an antibody against a CYP2D isoenzyme. The profiles of these decreased metabolic activities corresponded to that of the lower metabolic activities in Dark-Agouti rats. These results indicated that a cytochrome P450 isozyme in the CYP2D subfamily was involved in E- and Z-10-hydroxylations of amitriptyline and nortriptyline in rat liver microsomes as a major isozyme in a low substrate concentration range. It seems likely that the CYP2D enzyme contributes to nortriptyline N-demethylation.