阿魏酸钠对乙醇所致小鼠肝脏抗氧化功能改变的拮抗作用

研究了不同剂量乙醇对小鼠抗氧化和解毒功能的影响以及阿魏酸钠的拮抗作用。结果表明,大剂量乙醇(11.4g·kg^-1ig)引起肝脏GSH-Px活性升高的同时,肝脏GSH-Re,SOD和GST活性降低,GSH耗竭,而血清GST升高;阿魏酸钠(100mg·kg^-1ig,qd×10)预处理则明显拮抗大剂量乙醇所致的上述改变。表明阿魏酸钠对急性乙醇所致肝损害具有良好保护作用,其机理可能与提高GSH氧化还原酶功能、增加SOD活性和增强GSH结合反应有关。研究结果还提示,血清GST水平是反映乙醇性肝损害的灵敏指标。     

Effects of managed care on alcohol and other drug (AOD) treatment

The article represents the proceedings of a symposium at the 2001 RSA Meeting in Montreal, Canada. The organizer/chair was Stephen Magura. The presentations examined: (1) How managed care organization policies may affect enrollees' use of alcohol and other drug (AOD) treatment, by Constance Horgan and associates; (2) The determinants of patients' access to and utilization of AOD treatment in a large health maintenance organization, by Jennifer R. Mertens and Constance Weisner; (3) The impact on treatment access and costs of a statewide carve-out for AOD treatment for Medicaid, by Donald Shepard and associates; and (4) The predictive validity of a new patient assessment technology developed, in part, to better justify AOD treatment in response to the demands of managed care, by Stephen Magura and associates.     

Nox4 oxidase overexpression specifically decreases endogenous Nox4 mRNA and inhibits angiotensin II-induced adventitial myofibroblast migration

The vascular adventitia is emerging as an important modulator of vessel remodeling. Adventitial myofibroblasts migrate to the neointima after balloon angioplasty, contributing to restenosis. We postulated that angiotensin II (Ang II) enhances adventitial myofibroblast migration in vitro via reduced nicotinamide-adenine dinucleotide phosphate oxidase-derived H(2)O(2) and that Nox4-based oxidase promotes migration. Ang II increased myofibroblast migration in a concentration-dependent manner, with a peak increase of 1023+/-83%. Rat adventitial myofibroblasts were cotransfected with human Nox4 and human p22-phox plasmids or an empty vector. PCR showed an 8-fold increase in human Nox4 and human p22-phox plasmid expression. Using RT-PCR with primers specifically designed for rat reduced nicotinamide-adenine dinucleotide phosphate oxidases, endogenous Nox levels were determined. Ang II decreased endogenous Nox4 and Nox1 mRNA to 41% and 27% of control, respectively, but had no effect on Nox2. Cotransfection with human Nox4 and human p22-phox plasmids combined with Ang II reduced endogenous Nox4 mRNA levels (37+/-5% of control; P<0.05), whereas it had no significant effect on Nox1 or Nox2. In empty vector-transfected cells, Ang II increased myofibroblast migration by 192+/-32% versus vehicle (P<0.01) while increasing H(2)O(2) (473+/-22% versus control; P<0.001). Cotransfection with human Nox4 and human p22-phox plasmids decreased Ang II-induced migration (46+/-6%; P<0.001) in parallel with attenuation of H(2)O(2) production (23+/-8% versus empty vector; P<0.05). Our data suggest that Nox4 promotes Ang II-induced myofibroblast migration via an H(2)O(2)-dependent pathway. The data also suggest that Nox4 causes feedback inhibition of its own expression in adventitial myofibroblasts.     

RNA binding determinant in some class I tRNA synthetases identified by alignment-guided mutagenesis.

The N-terminal nucleotide binding folds of all 10 class I tRNA synthetases (RSs) contain characteristic conserved sequence motifs that define this class of synthetases. Sequences of C-terminal domains, which in some cases are known to interact with anticodons, are divergent. In the 676-amino acid Escherichia coli methionyl-tRNA synthetase (MetRS), interactions with the methionine tRNA anticodon are sensitive to substitutions at a specific location on the surface of the C-terminal domain of this protein of known three-dimensional structure. Although four class I synthetases of heterogeneous lengths and unknown structures are believed to be historically related to MetRS, pair-wise sequence similarities in the region of this RNA binding determinant are obscure. A multiple alignment of all sequences of three of these synthetases with all MetRS sequences suggested a location for the functional analog of the anticodon-binding site in these enzymes. We chose a member of this set for alignment-guided mutagenesis, combined with a functional analysis of mutant proteins. Substitutions within two amino acids of the site fixed by the multiple sequence alignment severely affected interactions with tRNA but not with ATP or amino acid. Multiple individual replacements at this location do not disrupt enzyme stability, indicating this segment is on the surface, as in the MetRS structure. The results suggest the location of an RNA binding determinant in each of these three synthetases of unknown structure.     

Orlistat fails to alter postprandial plasma lipid excursions or plasma lipases in normal-weight male volunteers

OBJECTIVES: After 10 d of orlistat administration (120 mg three times/day), the primary objective was to determine the drug's effect on postprandial plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities on day 10 after an oral fat-load. The secondary objectives were to determine the effects of orlistat on 12 h postprandial measures of: (1) preheparin HTGL and LPL; and (2) serum triglycerides, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and free fatty acids. METHODS: Twenty-four normal-weight, healthy male volunteers were randomized to either 120 mg orlistat (n=12) or placebo (n=12) three times a day with meals for 10 d. Preheparin LPL and HTGL activities and LPL specific activity were measured in the fasted state on days 1, 5, and 10. On days 5 and 10 the study medication (orlistat or placebo) was taken at the beginning of a fat-rich breakfast and serum lipid and lipoprotein levels monitored for 12 h postprandially. On day 10, 15 min postheparin HTGL activity was measured 8 h after the fat-rich breakfast. RESULTS: No differences were found between groups in fasting levels of preheparin LPL or HTGL activity or in LPL-specific activity on days 1, 5 and 10. No difference was found between the two treatment groups in postheparin HTGL activity 8 h after the fat-rich breakfast. Also, no differences were found between the two groups in plasma triglycerides or lipoproteins. CONCLUSION: The results indicate that the oral administration of orlistat (120 mg t. i.d.) does not significantly alter plasma triglycerides or lipoproteins, and that the inhibitory effect of orlistat on lipases is limited to the gastrointestinal tract and is not manifested systemically.     

MAPLE Deposition of Macromolecules

Macromolecules are poised to feature prominently as components in organic electronics, medical implants, drug delivery systems, and sensors. A common theme for the role polymers will play in all of these is as a thin film. In all applications, it is paramount to have precise control over film thickness, structure, morphology, surfaces roughness, etc. Here, matrix‐assisted pulsed laser evaporation (MAPLE) is reviewed as a route to processing polymer and other soft matter thin films with control over the above‐mentioned parameters. After briefly discussing the experimental setup and current proposed mechanism of film formation via MAPLE, the use of MAPLE to process thin films is highlighted for use in various technologies and applications. Future directions and challenges for MAPLE processing of thin films are also discussed.