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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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We have studied the effects of semi-synthetic diets rich in either n-9 (olive oil, OO) or n-6 (corn oil, CO), or n-3 (fish oil, FO, as MaxEPA) fatty acids on the levels of major PUFA in platelet lipids, on the generation of inositol phosphates by [3H]inositol labelled platelets after stimulation with thrombin and of thromboxane B2 (TxB2) by platelet rich plasma (PRP) after stimulation with collagen. The predicted elevations of oleic (OA), linoleic (LA) and eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were observed in platelet lipids of each animal group, but in the MaxEPA fed group accumulation of EPA was associated with depletion of linoleic acid (LA) rather than of arachidonic acid (AA). Basal levels of inositol-tris-phosphate (IP3) in platelets were lowest in the OO group and highest in the CO group, whereas the increment after thrombin stimulation (1 unit/ml NIH) was maximal in the OO group and minimal in the FO group. Instead, when generation of TxB2 by stimulated platelets was evaluated, no appreciable difference among the various groups could be detected, in accordance with the limited modifications of platelet AA content induced by the diets. The overall data indicate that dietary fatty acids modulate the pathway of inositol phosphate generation in rabbit platelets, independently of modifications of TxB2 production. 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8.
Luigi La Vecchia Paolo Vincenzi Luca Favero Manuela Martini Andrea Rubboli Filippo Ottani Leonardo Varotto Alessandro Fontanelli 《Italian heart journal》2004,5(10):749-754
BACKGROUND: Recent studies evaluated the technique of direct coronary stenting as compared to stenting-after-predilation in selected anatomic and clinical settings. However, the impact of direct stenting in routine interventional practice remains poorly elucidated. METHODS: From April 1999 to March 2001, all percutaneous coronary interventions performed at our Center were prospectively analyzed to determine the frequency of direct stenting, the success rate and the variables associated with its utilization. RESULTS: 1151 lesions were treated in 835 procedures. Stenting was attempted in 835/1151 lesions (72.5%), 309 (37%) with direct stenting and 526 (63%) with stenting-after-predilation. Direct stenting was successful in 300/309 (97%) and stenting-after-predilation in 515/526 (98%). The success rate of direct stenting was significantly lower in small vessels (< or = 2.75 mm) (89.2 vs 98.5%, p = 0.005). Patients treated with direct stenting were younger (63 +/- 11 vs 65 +/- 11 years, p = 0.024). Direct stenting was preferentially used in saphenous vein grafts and at the ostium of the left anterior descending coronary artery, while it was avoided in bifurcation lesions and with increasing calcium burden. Operators with a caseload > 140 interventions per year were significantly more likely to perform direct stenting than less experienced operators (p = 0.017). In direct stenting, the total contrast medium and the fluoroscopy and procedural times were all significantly (p < 0.0001) lower than those observed in case of stenting-after-predilation. CONCLUSIONS: Direct coronary stenting is currently performed in about one third of the overall caseload. Variables pertaining to the operator's experience, lesion morphology and length, vessel size, and the clinical presentation are all important factors determining the selection of candidates suitable for direct stenting. 相似文献
9.
Lupus anticoagulant IgG's (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin. 总被引:25,自引:0,他引:25
Plasmas from 16 patients that were found to be positive both for anticardiolipin antibodies (ACA) and lupus anticoagulants (LA) were incubated with liposomes that contained anionic phospholipids. In 11 of these plasmas, ACA could be cosedimented with the liposomes in a dose-dependent manner, whereas LA activity of the remaining supernatant was unaffected. LA activity of purified total IgG from 6 patients was measured in three different coagulation tests, using normal plasmas from different species. Prolongation of the aPTT, KCT and dRVV clotting times was observed only with normal plasma from human origin, not with bovine, rat or sheep plasma. Highly purified coagulation factors Xa, Va and prothrombin, both of human and bovine origin, were used to establish for two patient IgG's the effect of LA on the rate of thrombin formation in the presence and absence of lipid vesicles composed of 20 mole% phosphatidylserine and 80 mole% phosphatidylcholine. A strong and dose dependent inhibition by LA was observed only when human prothrombin was used as substrate in the prothrombinase complex in the presence of lipids. No inhibition was found when bovine prothrombin was used as substrate. The inhibitory effect observed in the presence of human prothrombin was independent of the source of factors Xa and Va, and was not found in the absence of lipid. Preliminary binding studies suggest that LA only associate with a lipid surface, provided that human prothrombin and calcium ions are present. These data indicate that LA are not directed to phospholipids alone, but presumably recognize an epitope which becomes exposed upon Ca(2+)-mediated binding of human prothrombin to phospholipids. 相似文献
10.