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排序方式: 共有7568条查询结果,搜索用时 15 毫秒
1.
Peter Chiba Barbara Tell Walter Jger Elisabeth Richter Manuela Hitzlera Gerhard Ecker 《Archiv der Pharmazie》1997,330(11):343-347
A series of 5-hydroxy and 5-benzyloxy analogs of the antiarrhythmic and multidrug resistance (MDR) modulating drug propafenone was synthesized and the MDR-modulating activity of the compounds was evaluated using a daunomycin efflux assay system. The key step of the synthesis is the selective reduction of the double bond in 1 without cleavage of the benzyl group thus leading to the phenol 3 . Alkylation with epichlorohydrine followed by nucleophilic epoxide ring opening gave the benzylated target compounds 5a–d . Subsequent cleavage of the benzyl group gave the 5-hydroxy analogs 6a–d . Structure activity relationship studies showed, that the 5-hydroxy derivates 6a–d fit the log P/log potency correlation line previously established for a series of propafenone analogs. In contrast, all four 5-benzyloxy analogs 5a–d showed almost identical EC50 values, independent of their log P value. 相似文献
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Manuela Kusch Claudia Grundmann Stefanie Keitel Rainer Seitz Herbert K?nig 《Blood coagulation & fibrinolysis》2006,17(7):575-580
A novel assay for factor XIII is described that utilizes exclusively small synthetic peptides as substrates for the cross-linking reaction catalyzed by activated factor XIII (FXIIIa). The acyl donor substrate (selection peptide) is immobilized on a microplate via biotin while the acyl acceptor substrate (detection peptide) is labeled with the fluorochrome Oregon green to allow sensitive detection without the need for secondary enzyme systems for signal amplification. Starting with an amino acid sequence from the fibrin gamma-chain (GQQHHLGGAKQAGDV) as a prototype peptide, the influence of amino acid exchanges were investigated with respect to their impact on the FXIIIa-catalyzed reaction. It was found that FXIIIa readily accepts a broad range of substrate peptides, with a proline neighboring the essential lysine having the most detrimental effect. The assay appears to be valuable for the molecular characterization of factor XIII and may be used for a deeper investigation into the substrate requirements of this final enzyme of wound repair, and eventually also for the characterization of other transglutaminases. 相似文献
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Factors affecting aseptic loosening of 4750 total hip arthroplasties: multivariate survival analysis
Barbara Bordini Susanna Stea Manuela De Clerico Sergio Strazzari Antonio Sasdelli Aldo Toni 《BMC musculoskeletal disorders》2007,8(1):69
Background
Total hip arthroplasty is a successful surgery, that fails at a rate of approximately 10% at ten years from surgery. Causes for failure are mainly aseptic loosening of one or both components partially due to wear of articular surfaces and partially to design. The present analysis aimed to identify risk factors and quantify their effects on aseptic failure. 相似文献7.
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Wolfgang G Rehwald Michael Salerno Enn-Ling Chen Burkhard Sievers Raymond J Kim Robert M Judd 《Magnetic resonance in medicine》2007,58(1):82-91
To extend the signal longevity of magnetically excited spins in flowing fluids while in a state of global coherent free precession (GCFP), a refocusing radiofrequency (RF) pulse and bipolar gradient waveforms were combined with the GCFP sequence. The data demonstrate that RF refocusing in the presence of flowing blood is possible, but the improvement in signal amplitude depends on the static magnetic field homogeneity along the direction of motion and the displacement of the spins between the excitation and the RF refocusing pulse, as well as displacement during subsequent RF refocusing pulses. The least amount of phase dispersion and thus the longest lasting signal is obtained with the shortest echo spacing where only one line of data is recorded between two RF refocusing pulses. This approach was successfully used in a phantom and in vivo to image fast and slow blood flow. Depending on the experimental conditions, signal persistence is improved significantly compared to playing the same sequence without RF refocusing, but the improvement is limited by the product of blood flow velocity and the time between RF refocusing pulses. 相似文献
9.
Hypertonic sodium bicarbonate (HSB) has been reported to reduce the toxicity of Class IC antiarrhythmic agents in rats and, anecdotally, in patients. A pilot study was conducted of the safety and efficacy of HSB for reversing the electrocardiographic effects of therapeutic doses of encainide or flecainide in ten patients taking these drugs for chronic ventricular arrhythmias. Patients had a mean drug-induced QRS prolongation before treatment of 27.6 +/- 8.8%. Each patient received a single dose of HSB 100 mEq or normal saline IV over 5 minutes on two separate occasions. The administration of treatments was blinded and balanced. There were no important side effects of HSB. Venous blood pH, CO2 content and sodium concentration were all significantly increased by HSB in comparison to saline. No differences were found during the 2-hour observation period in the primary endpoint, QRS duration, the PR or QT intervals, or the frequency of premature ventricular beats. It was concluded that HSB 100 mEq does not reduce QRS duration in patients taking therapeutic doses of flecainide or encainide. Because HSB was well tolerated, investigation of its use in higher doses or in patients with overt toxicity due to Class IC drugs is feasible. 相似文献
10.
P J O'Brien E Ling H M Williams S Brotherton T Salerno J H Lumsden C D Ianuzzo 《The Canadian journal of cardiology》1988,4(5):243-250
This study was undertaken to test the hypothesis that a compensatory response of the heart to a chronic and continuous, metabolic and heart rate overload was an increase in the calcium sequestering activity of the myocardial sarcoplasmic reticulum. Calcium sequestering activity was estimated by determination of the calcium-dependent ATPase (Ca2+-ATPase) activity of isolated microsomes. Chronic rate overload was modelled by comparing: dysthyroid and control rats; control swine and swine with implanted cardiac pacemakers set at 180 beats/min; and different species of mammals with widely different heart rates. The myocardial sarcoplasmic reticulum Ca2+-ATPase pump activity was significantly increased by 39% for hyperthyroid rats compared to control rats and by 87% for control rats compared to thyroidectomized rats; by 63% for paced swine compared to control swine; and by 43% for rats compared to guinea pigs, by 140% for guinea pigs compared to dogs and by 120% for dogs compared to cows. These data indicate that calcium sequestering activity of myocardial sarcoplasmic reticulum increases in equivalent proportion to the chronotropic demand and that heart rate is a hemodynamic correlate of the sarcoplasmic reticulum Ca2+-ATPase activity. 相似文献