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991.
Madurahydroxylactone derivatives as dual inhibitors of human immunodeficiency virus type 1 integrase and RNase H
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Marchand C Beutler JA Wamiru A Budihas S Möllmann U Heinisch L Mellors JW Le Grice SF Pommier Y 《Antimicrobial agents and chemotherapy》2008,52(1):361-364
A series of 29 madurahydroxylactone derivatives was evaluated for dual inhibition of human immunodeficiency virus type 1 (HIV-1) integrase and RNase H. While most of the compounds exhibited similar potencies for both enzymes, two of the derivatives showed 10- to 100-fold-higher selectivity for each enzyme, suggesting that distinct pharmacophore models could be generated. This study exemplifies the common and divergent structural requirements for the inhibition of two structurally related HIV-1 enzymes and demonstrates the importance of systematically screening for both integrase and RNase H when developing novel inhibitors. 相似文献
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994.
Resynchronization: What if the Left Ventricular Lead Cannot Reach the Lateral or Posterolateral Wall? 总被引:2,自引:0,他引:2
Background: The recommended left ventricular (LV) lead position for cardiac resynchronization therapy (CRT) is at the lateral or posterolateral wall. However, LV leads cannot always be implanted at this site. The objective of our study was to compare the clinical response to CRT when the LV lead could be implanted or not at the lateral or posterolateral wall.
Methods: In consecutive patients implanted with a CRT device, we documented the final position achieved by the tip of the LV lead in the left anterior oblique projection. Patients were prospectively followed for 6 months after implantation. They were defined as responders if they were alive, had gained 1 New York Heart Association (NYHA) functional class, and had not been hospitalized for heart failure.
Results: The study population consisted of 77 patients (56 men, 71 ± 10 years, 62 NYHA class III, 15 NYHA class IV). The LV lead was implanted at the lateral or posterolateral wall in 54 patients (group A) and at the anterior or anterolateral wall in 23 patients (group B). At 6 months, seven patients (9%) died (all in group A). There were 37 responders (69%) in group A as compared to 22 (96%) in group B.
Conclusions: The responder rate was not inferior when the LV lead was implanted at the anterior or anterolateral wall. Thus, in case of failed implantation at the lateral or posterolateral wall, positioning the LV lead in a more anterior location appears to be a reasonable alternative. Further studies are required to confirm these findings. 相似文献
Methods: In consecutive patients implanted with a CRT device, we documented the final position achieved by the tip of the LV lead in the left anterior oblique projection. Patients were prospectively followed for 6 months after implantation. They were defined as responders if they were alive, had gained 1 New York Heart Association (NYHA) functional class, and had not been hospitalized for heart failure.
Results: The study population consisted of 77 patients (56 men, 71 ± 10 years, 62 NYHA class III, 15 NYHA class IV). The LV lead was implanted at the lateral or posterolateral wall in 54 patients (group A) and at the anterior or anterolateral wall in 23 patients (group B). At 6 months, seven patients (9%) died (all in group A). There were 37 responders (69%) in group A as compared to 22 (96%) in group B.
Conclusions: The responder rate was not inferior when the LV lead was implanted at the anterior or anterolateral wall. Thus, in case of failed implantation at the lateral or posterolateral wall, positioning the LV lead in a more anterior location appears to be a reasonable alternative. Further studies are required to confirm these findings. 相似文献
995.
Where Are the Left Ventricular Leads Really Implanted? A Study of 90 Consecutive Patients 总被引:1,自引:0,他引:1
Background: Cardiac resynchronization therapy (CRT) is a recognized treatment for severe heart failure. The recommended left ventricular (LV) lead position is at the lateral or posterolateral wall. However, LV leads cannot always be implanted at the expected site. The aim of our study was to describe in a large series of patients the anatomical position really achieved by LV leads at implant.
Method: In consecutive patients referred for CRT, we determined the LV lead implantation success rate, the success rate for the initial target vein, and the final position achieved by the tip of the LV lead in the left and right anterior oblique projections.
Results: Ninety patients (66 men, 71 ± 9 years, 20% New York Heart Association (NYHA) class IV) were referred for an LV lead implantation between September 2003 and March 2006. A LV lead could be implanted in 92% of patients. In 70%, LV leads were implanted in the initial target vein. The final location was lateral or posterolateral in 68% and anterior or anterolateral in 32% of patients. The mean procedural time was 117 ± 42 minutes.
Conclusions: LV lead implantation was achieved in 92% of patients with mean procedure duration of less than 2 hours. Nevertheless, 30% of LV leads were implanted outside of the initial target vein and 32% at the anterior or anterolateral wall. Further studies are warranted to compare the responder rate to CRT when the LV lead is at the lateral or posterolateral wall or when the LV lead is at an alternative site. 相似文献
Method: In consecutive patients referred for CRT, we determined the LV lead implantation success rate, the success rate for the initial target vein, and the final position achieved by the tip of the LV lead in the left and right anterior oblique projections.
Results: Ninety patients (66 men, 71 ± 9 years, 20% New York Heart Association (NYHA) class IV) were referred for an LV lead implantation between September 2003 and March 2006. A LV lead could be implanted in 92% of patients. In 70%, LV leads were implanted in the initial target vein. The final location was lateral or posterolateral in 68% and anterior or anterolateral in 32% of patients. The mean procedural time was 117 ± 42 minutes.
Conclusions: LV lead implantation was achieved in 92% of patients with mean procedure duration of less than 2 hours. Nevertheless, 30% of LV leads were implanted outside of the initial target vein and 32% at the anterior or anterolateral wall. Further studies are warranted to compare the responder rate to CRT when the LV lead is at the lateral or posterolateral wall or when the LV lead is at an alternative site. 相似文献
996.
997.
Ventura G De Bandt JP Segaud F Perret C Robic D Levillain O Le Plenier S Godard C Cynober L Moinard C 《The British journal of nutrition》2009,101(6):843-851
Ornithine aminotransferase (OAT) is a reversible enzyme expressed mainly in the liver, kidney and intestine. OAT controls the interconversion of ornithine into glutamate semi-aldehyde, and is therefore involved in the metabolism of arginine and glutamine which play a major role in N homeostasis. We hypothesised that OAT could be a limiting step in glutamine-arginine interconversion. To study the contribution of the OAT enzyme in amino acid metabolism, transgenic mice that specifically overexpress human OAT in the liver, kidneys and intestine were generated. The transgene expression was analysed by in situ hybridisation and real-time PCR. Tissue (liver, jejunum and kidney) OAT activity, and plasma and tissue (liver and jejunum) amino acid concentrations were measured. Transgenic male mice exhibited higher OAT activity in the liver (25 (sem 4) v. 11 (sem 1) nmol/min per microg protein for wild-type (WT) mice; P < 0.05) but there were no differences in kinetic parameters (i.e. Km and maximum rate of reaction (Vmax)) between WT and transgenic animals. OAT overexpression decreased plasma and liver ornithine concentrations but did not affect glutamine or arginine homeostasis. There was an inverse relationship between ornithine levels and OAT activity. We conclude that OAT overexpression has only limited metabolic effects, probably due to the reversible nature of the enzyme. Moreover, these metabolic modifications had no effect on phenotype. 相似文献
998.
Rochais C Duc NV Lescot E Sopkova-de Oliveira Santos J Bureau R Meijer L Dallemagne P Rault S 《European journal of medicinal chemistry》2009,44(2):708-716
We herein describe the synthesis of novel dipyrrolo- and furopyrrolopyrazinones related to highly cytotoxic tripentones and to their oximes. The synthetic pathway involved in particular a Curtius rearrangement and a subsequent cyclisation into the title pyrazinones. The biological evaluation towards various cyclin-dependent kinases (CDKs1-5, GSK-3) highlighted a weak inhibitory activity for the oximes whose SAR was studied by a molecular modeling study. 相似文献
999.
1000.
Tuntipopipat S Zeder C Siriprapa P Charoenkiatkul S 《International journal of food sciences and nutrition》2009,60(Z1):43-55
Spices and herbs are extensively used in indigenous diets in tropical regions where prevalence of iron deficiency is still high. They are rich in polyphenolic compounds that are expected to inhibit iron absorption by forming iron complexes in the intestine, making dietary iron less available for absorption. The effects of six spices and herbs (chili pepper, garlic, 'Pak kyheng' (Thai leafy vegetable), shallot, tamarind, turmeric) and one mixture of spices (curry paste) on iron availability were determined by measuring the percentage dialyzable iron after addition of spices and herbs to a rice meal after simulated digestion. All tested spices and herbs contained from 0.5 to 33 mg polyphenol per meal and were potent inhibitors of iron availability (20-90%), reducing iron availability in a dose-dependent manner--with the exception of tamarind, which at 11 mg polyphenol per meal enhanced iron availability. Our findings demonstrate that culinary spices and herbs can play an important role in iron nutrition. 相似文献