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991.
LL von Moltke DJ Greenblatt JM Grassi BW Granda K Venkatakrishnan J Schmider JS Harmatz RI Shader 《Canadian Metallurgical Quarterly》1998,50(9):997-1004
Cytochromes mediating the biotransformation of dextromethorphan to dextrorphan and 3-methoxymorphinan, its principal metabolites in man, have been studied by use of liver microsomes and microsomes containing individual cytochromes expressed by cDNA-transfected human lymphoblastoid cells. In-vitro formation of dextrorphan from dextromethorphan by liver microsomes was mediated principally by a high-affinity enzyme (Km (substrate concentration producing maximum reaction velocity) 3-13 microM). Formation of dextrorphan from 25 microM dextromethorphan was strongly inhibited by quinidine (IC50 (concentration resulting in 50% inhibition) = 0.37 microM); inhibition by sulphaphenazole was approximately 18% and omeprazole and ketoconazole had minimal effect. Dextrorphan was formed from dextromethorphan by microsomes from cDNA-transfected lymphoblastoid cells expressing CYP2C9, -2C19, and -2D6 but not by those expressing CYP1A2, -2E1 or -3A4. Despite the low in-vivo abundance of CYP2D6, this cytochrome was identified as the dominant enzyme mediating dextrorphan formation at substrate concentrations below 10 microM. Formation of 3-methoxy-morphinan from dextromethorphan in liver microsomes proceeded with a mean Km of 259 microM. For formation of 3-methoxymorphinan from 25 microM dextromethorphan the IC50 for ketoconazole was 1.15 microM; sulphaphenazole, omeprazole and quinidine had little effect. 3-Methoxymorphinan was formed by microsomes from cDNA-transfected lymphoblastoid cells expressing CYP2C9, -2C19, -2D6, and -3A4, but not by those expressing CYP1A2 or -2E1. CYP2C19 had the highest affinity (Km = 49 microM) whereas CYP3A4 had the lowest (Km = 1155 microM). Relative abundances of the four cytochromes were determined in liver microsomes by use of the relative activity factor approach. After adjustment for relative abundance, CYP3A4 was identified as the dominant enzyme mediating 3-methoxymorphinan formation from dextromethorphan, although CYP2C9 and -2C19 were estimated to contribute to 3-methoxymorphinan formation, particularly at low substrate concentrations. Although formation of dextrorphan from dextromethorphan appears to be sufficiently specific to be used as an in-vitro or in-vivo index reaction for profiling of CYP2D6 activity, the findings raise questions about the specificity of 3-methoxymorphinan formation as an index of CYP3A activity. 相似文献
992.
M Reck B Haering G Koschel E Kaukel J von Pawel U Gatzemeier 《Canadian Metallurgical Quarterly》1998,52(10):570-573
In the palliative treatment of advanced SCLC and NSCLC there is a big need for effective and well tolerable drugs. Bendamustin is an alcylatic agent which had shown activity in the treatment of Non Hodgkin- and Hodgkin-Lymphoma as well as in the treatment of solid tumors like Mamma-Carcinoma and Colorectal-Carcinoma. We treated 21 patients with NSCLC (5 pat. Stad. III b, 16 pat. Stad. IV) and 22 pat. with Extensive Disease SCLC with Bendamustin 70 mg/m2 i.v., day 1-4 (q.28 days). We observed a response rate of 40.9% in the patients with SCLC (9 PR/40.9%), (0 CR) and no response in the patients with NSCLC. Hematologic toxicity in both groups was mild (Leucopenia WHO 1 + 2: 13 pat./30.2%, WHO 3: 2 pat./4.6%; Anemia WHO 1 + 2: 13 pat./30.2%, WHO 3: 1 pat./2.4%; Thrombopenia WHO 1 + 2: 4 pat./9.6%, WHO 3: 1/2.4%). Non Hematologic toxicity consisting of Nausea/Vomiting (WHO 2 + 3:13 pat./30.2%), Diarrhea (WHO 2 + 3:3 pat./7%), Obstipation (WHO 1 + 2: 2 pat./4.6%), Fever (WHO 1 + 2: 9 pat./20.9%) and Alopecia (WHO 1 + 2: 13 pat./31.7%, WHO 3: 1 pat./2.4%) was well tolerable. Cardiac Arrhythmias occurred in 7 pat./16.3% and PNP in 2 pat./4.6%. Treatment had to be stopped in one patient because of an allergic skin reaction. Bendamustin is a well tolerable cytostatic drug with a remarkable activity in advanced SCLC which is comparable to other well known agents in the treatment of this disease. Because of the good toxicity profile a combination with other compounds might be feasible. In advanced NSCLC Bendamustin showed no activity. 相似文献
993.
Three different vaccination sites were compared for efficiency of immunization with naked DNA. Using the bacterial lacZ gene as a model, all three sites of the mouse (skeletal muscle, dermis of abdominal skin or of the ear pinna) could express the gene product beta-gal but varied in expression time with muscle tissue showing the longest expression. Expression time, however, did not correlate with immune response intensity. The ear pinna was by far the most effective and muscle the least effective priming site for specific humoral and cytotoxic T cell-mediated immune responses. Following intra-pinna DNA inoculation, beta-gal expressing cells were detectable around the injection site and in the major draining lymph node. Efficiency of immunization was also dependent on the promoter and expression vector used. The cytomegalus virus promoter driven pCMV beta vector was superior to the Moloney murine leukemia virus LTR driven BAG vector. LacZ DNA immunization was also compared with cell-based vaccination with lacZ-transfected tumor cells, in which case again the pinna was the best site for inducing strong immune responses. Tumor-specific T cell responses could also be well induced in the pinna, leading to cytotoxic T lymphocyte induction and protective antitumor immunity. Thus, the pinna was found to be a privileged site for induction of antitumor responses and for genetic immunization, an important finding of immediate practical and potential future clinical implications. 相似文献
994.
Crystallization kinetics of the three main components of cocoa butter, the triacylglycerols POP, POS, and SOS (where P, O,
and S stand for palmitic, oleic, and stearic acids, respectively) were studied by combined differential scanning calorimetry
and polarized light microscopy. The morphologies, nucleation kinetics, growth kinetics, and phases of the grains formed were
identified with this system. The experimental data, as well as two different models to simulate crystallization and to predict
behavior of the pure triacylglycerols, are presented. The first model is based on a macroscopical approach to solidification
by using time-temperature-transformation (TTT) diagrams and the additivity principle. It allows prediction of the proportion
of the different phases formed for any given thermal path imposed on the sample once the TTT diagram is known for the product.
It is illustrated for SOS at constant cooling rates and is compared with experimental results. The second model directly simulates
growth of the spherulites in the sample by using nucleation and growth rates that are determined experimentally. It provides
a view of the structure as it would be observed with a microscope and shows evolution of the heat released in the sample.
Isothermal solidification of POP at 15°C is displayed. The experiment and the model are in good agreement. 相似文献
995.
RC von Borstel 《Canadian Metallurgical Quarterly》1994,266(5188):1144-1145
996.
This article presents a reliability analysis of 116 full-scale pond systems in Brazil, comprising 73 primary facultative ponds and 43 anaerobic -facultative pond systems. A methodology developed by Niku et al. (1979) is used for the determination of the coefficients of reliability, in terms of the compliance of effluent BOD, COD, TSS and FC to discharge standards or effluent quality targets. The design concentrations necessary to meet the prevailing discharge standards and the expected compliance percentages have been calculated from the coefficients of reliability obtained. The results showed that few units, under the observed operating conditions, would be able to present reliable performances in terms of compliance with the analyzed standards. For the four constituents (BOD, COD, TSS and FC) and both systems (facultative ponds and anaerobic-facultative systems), the variability of the effluent quality was very large, leading to a high variability of the coefficient of variation (CV) and the coefficient of reliability (COR). The effluent quality from the facultative ponds showed a larger distance to both the desired values and the discharge standard values, compared with the anaerobic-facultative systems. 相似文献
997.
§ 31 Abs 5 o? BauO gew?hrt nur bei Neuerrichtungen Einwendungen gegen heranrückende Wohnbauten, nicht aber auch bei sonstigen,
wenn auch substantiellen Bauma?nahmen (hier: Umbau). 相似文献
998.
GM Kacl I Bicik AW Sch?nenberger P Steiner B Romanowski JF Debatin GK von Schulthess 《Canadian Metallurgical Quarterly》1998,8(7):1173-1178
The purpose of this review was to give an answer to the question whether there are convincing data to support the hypothesis of an amino acid imbalance as one possible mechanism to explain overtraining syndrome. Animal studies point to an enhanced synthesis of the neurotransmitter 5-hydroxytryptamine through an amino acid imbalance at the blood-brain barrier with a preferable tryptophan uptake into the brain, resulting in premature fatigue. Human studies, however, show contradictory results, mainly because of nonstandardized methodology, so that a final conclusion cannot be made at present. BCAA supplementation in addition to standard carbohydrate ingestion during sustained exercise seems to be of no eminent advantage to delay fatigue. The overall results concerning the BCAA hypothesis to explain overtraining are inconclusive and require more controlled experimental research. 相似文献
999.
1000.
The influence of running water on spray water cooling is experimentally looked at with the aid of a stationary working experimental plant. The running water was fed separately to the sample from above as a defined water film by using a slot nozzle. In addition to the spray nozzle pre-pressure, the velocity of the running water at the slot nozzle exit and the temperature of the running water, the angle of inclination of the sample plane was also varied. By employing three different full cone spray nozzles and setting different nozzle distances, a range of 450 to 2000 l/(m2·min) of the water impingement density was covered. To estimate the marginal influences, samples of 20 × 20 mm as well as 30 × 30 mm were used. Studies of initially pure spray water cooling without the additional running water film revealed a dependency of the heat transfer on the spray water impingement density, the spray water velocity and also the angle of inclination of the sample plane. For nozzles with a low water impingement density, a superimposing of a running water film on the spray water revealed a sharp increase in the heat transfer coefficients compared to pure spray water cooling. For nozzles with a high water impingement density and, therefore, with a high heat transfer already even for pure spray water cooling, the increase of the heat transfer coefficient is minor. 相似文献