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排序方式: 共有3333条查询结果,搜索用时 31 毫秒
41.
David C Bischoff L Meudal H Mothé A De Mota N DaNascimento S Llorens-Cortes C Fournié-Zaluski MC Roques BP 《Journal of medicinal chemistry》1999,42(25):5197-5211
The study of the physiological roles of the membrane-bound zinc-aminopeptidase A (glutamyl aminopeptidase, EC 3.4.11.7) needs the design of efficient and selective inhibitors of this enzyme. An acute exploration of aminopeptidase A active site was performed by a combinatorial approach using (3-amino-2-mercapto-acyl)dipeptides able to fit its S(1), S(1)', and S(2)' subsites. This analysis confirmed that the S(1) subsite is optimally blocked by a glutamate or isosteric residues and demonstrated that the S(1)' subsite is hydrophobic whereas the S(2)' subsite recognizes preferentially negatively charged residues derived from aspartic acid. The optimization of these structural parameters led to the synthesis of nanomolar and subnanomolar inhibitors of aminopeptidase A such as H(3)N(+)CH(CH(2)CH(2)SO(3)(-))CH(SH)CO-Ile-(3-COOH)Pro that exhibits a K(i) of 0.87 nM. The best compounds were synthesized by a stereochemically controlled route. These first described highly potent inhibitors could allow studies about the role of physiological substrates of APA such as angiotensin II and cholecystokinin CCK(8) in the central nervous system. 相似文献
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High rate of hematological responses to sorafenib in FLT3‐ITD acute myeloid leukemia relapsed after allogeneic hematopoietic stem cell transplantation
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Tiago De Freitas Sarah Marktel Simona Piemontese Matteo G. Carrabba Cristina Tresoldi Carlo Messina Maria Teresa Lupo Stanghellini Andrea Assanelli Consuelo Corti Massimo Bernardi Jacopo Peccatori Luca Vago Fabio Ciceri 《European journal of haematology》2016,96(6):629-636
Relapse represents the most significant cause of failure of allogeneic hematopoietic stem cell transplantation (HSCT) for FLT3‐ITD‐positive acute myeloid leukemia (AML), and available therapies are largely unsatisfactory. In this study, we retrospectively collected data on the off‐label use of the tyrosine kinase inhibitor sorafenib, either alone or in association with hypomethylating agents and adoptive immunotherapy, in 13 patients with post‐transplantation FLT3‐ITD‐positive AML relapses. Hematological response was documented in 12 of 13 patients (92%), and five of 13 (38%) achieved complete bone marrow remission. Treatment was overall manageable in the outpatient setting, although all patients experienced significant adverse events, especially severe cytopenias (requiring a donor stem cell boost in five patients) and typical hand‐foot syndrome. None of the patients developed graft‐vs.‐host disease following sorafenib alone, whereas this was frequently observed when this was given in association with donor T‐cell infusions. Six patients are alive and in remission at the last follow‐up, and four could be bridged to a second allogeneic HSCT, configuring a 65 ± 14% overall survival at 100 d from relapse. Taken together, our data suggest that sorafenib might represent a valid treatment option for patients with FLT3‐ITD‐positive post‐transplantation relapses, manageable also in combination with other therapeutic strategies. 相似文献
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José Tiago Sequeira Lopes da Silva Olga González Casas Verónica Bejarano Moguel Maria Lobo Pascua Antonio López-Santamaría Redondo Remigio Cordero Torres 《Gastroenterologia y hepatologia》2013
Somatostatin and somatostatin analogues are considered very useful for the treatment of hormone producing tumors and acute variceal bleeding. They have also been proposed for the treatment of acute pancreatitis and for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis although clinical trials have failed to show any efficacy. The authors report the case of a 45-year-old man, recently diagnosed of acromegaly, which developed an acute pancreatitis shortly after his first injection of lanreotide autogel. The patient developed a severe dilatation of his hypocontractile gallbladder with distension of the intra and extrahepatic biliary ducts, the choledochus and the main pancreatic duct, without lithiasis or other abnormalities at the papilla, which resolved spontaneously in a month. We consider that lanreotide most likely induced a functional spasm of the Sphincter of Oddi, with impairment of the biliary-pancreatic outflow, leading to an acute pancreatitis, and review the literature concerning this drug related pancreatitis. 相似文献
47.
Francisco C. Carnevale Airton Mota Moreira Alberto A. Antunes 《Cardiovascular and interventional radiology》2014,37(6):1602-1605
Prostatic artery embolization requires a refined technique to achieve good imaging and clinical success. The PErFecTED (Proximal Embolization First, Then Embolize Distal) technique has produced greater prostate ischemia and infarction than previously described methods with clinical improvement of lower urinary symptoms and lower recurrence rates. The microcatheter should cross any collateral branch to the bladder, rectum, corpus cavernosum, gonad, or penis and be placed distally into the prostatic artery before its branching to the central gland and peripheral zone. This technique allows better distribution of embolic material in the intraprostatic arteries and reduces risk of spasm or thrombus. Because benign prostatic hyperplasia develops primarily in the periurethral region of the prostate, the urethral group of arteries should be embolized first. Subsequent distal investigation and embolization completes occlusion and stasis of blood flow to the prostatic parenchyma. Since we added the second step to the PErFecTED technique, we have observed infarcts in all patients submitted to prostatic artery embolization. 相似文献
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José Robson Neves Cavalcanti Filho Tiago Fonseca Silva Woah Queiroz Nobre Larissa Isabela Oliveira de Souza Cristiane Santos Silva e Silva Figueiredo Regina Celia Bressan Queiroz de Figueiredo 《Pharmaceutical biology》2017,55(1):1521-1527
Context: Buchenavia tetraphylla (Aubl.) RA Howard (Combretaceae: Combretoideae) is an ethnomedicinal plant with reported antifungal action.Objective: This study evaluates the antimicrobial activity of B. tetraphylla leaf extracts against clinical isolates of Candida albicans. The morphological alterations, combinatory effects with fluconazole and the cytotoxicity of the active extract were analyzed.Materials and methods: Extracts were obtained using different solvents (hexane: BTHE; chloroform: BTCE; ethyl acetate: BTEE; and methanol: BTME). Antimicrobial activity was determined by the broth microdilution method using nine strains of C. albicans isolated from vaginal secretions and one standard strain (UFPEDA 1007).Results: All extracts showed anti-C. albicans activity, including against the azole-resistant strains. The MIC values ranged from 156 to 2500?μg/mL for the BTHE; 156 to 1250?μg/mL for the BTCE; 625 to 1250?μg/mL for the BTME and 625?μg/mL to 2500?μg/mL for the BTEE. BTME showed the best anti-C. albicans activity. This extract demonstrated additive/synergistic interactions with fluconazole. Scanning electron microscopy analysis suggested that the BTME interferes with the cell division and development of C. albicans. BTME showed IC50 values of 981 and 3935?μg/mL, against J774 macrophages and human erythrocytes, respectively. This extract also enhanced the production of nitric oxide by J774 macrophages.Discussion and conclusion: Buchenavia tetraphylla methanolic extract (BTME) is a great source of antimicrobial compounds that are able to enhance the action of fluconazole against different C. albicans strains; this action seems related to inhibition of cell division. 相似文献
50.
Screening of candidate biomaterials for alveolar augmentation using a critical‐size rat calvaria defect model
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