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排序方式: 共有979条查询结果,搜索用时 15 毫秒
971.
Ballatore C Soper JH Piscitelli F James M Huang L Atasoylu O Huryn DM Trojanowski JQ Lee VM Brunden KR Smith AB 《Journal of medicinal chemistry》2011,54(19):6969-6983
Cyclopentane-1,3-diones are known to exhibit pK(a) values typically in the range of carboxylic acids. To explore the potential of the cyclopentane-1,3-dione unit as a carboxylic acid isostere, the physical-chemical properties of representative congeners were examined and compared with similar derivatives bearing carboxylic acid or tetrazole residues. These studies suggest that cyclopentane-1,3-diones may effectively substitute for the carboxylic acid functional group. To demonstrate the use of the cyclopentane-1,3-dione isostere in drug design, derivatives of a known thromboxane A(2) prostanoid (TP) receptor antagonist, 3-(3-(2-(4-chlorophenylsulfonamido)ethyl)phenyl)propanoic acid (12), were synthesized and evaluated in both functional and radioligand-binding assays. A series of mono- and disubstituted cyclopentane-1,3-dione derivatives (41-45) were identified that exhibit nanomolar IC(50) and K(d) values similar to 12. Collectively, these studies demonstrate that the cyclopentane-1,3-dione moiety comprises a novel isostere of the carboxylic acid functional group. Given the combination of the relatively strong acidity, tunable lipophilicity, and versatility of the structure, the cyclopentane-1,3-dione moiety may constitute a valuable addition to the palette of carboxylic acid isosteres. 相似文献
972.
Monika A. Kwiatek Peter J. Kahrilas Nathaniel J. Soper William J. Bulsiewicz Barry P. McMahon Hans Gregersen John E. Pandolfino 《Journal of gastrointestinal surgery》2010,14(2):268-276
Objective
The aim of the study was to compare the esophagogastric junction (EGJ) compliance in response to controlled distension in fundoplication (FP) patients and controls using the functional luminal imaging probe (FLIP). 相似文献973.
974.
Purpose
Single-incision laparoscopy (SIL) is potentially less invasive compared with standard laparoscopic surgery (LAP); however, it may be more technically challenging and have a longer learning curve. A two-phase study was conducted to examine the performance of standardized tasks on a surgical simulator by novices during a distributed training period. Phase 1 examined the effect of LAP-specific or SIL-specific training on skill acquisition for both techniques. Phase 2 compared the effectiveness and learning curves of additional instrument types for SIL (straight [STR] vs. dynamic articulating [D-ART]). 相似文献975.
Byron F. Santos Edward D. Auyang Eric S. Hungness Kush R. Desai Edward S. Chan Darren B. van Beek Edward C. Wang Nathaniel J. Soper 《Surgical endoscopy》2011,25(4):1168-1175
Background
Extraction of a gallbladder through an endoscopic overtube during natural orifice translumenal endoscopic surgery (NOTES?) transgastric cholecystectomy avoids potential injury to the esophagus. This study examined the rate of successful gallbladder specimen extraction through an overtube and hypothesized that preoperative ultrasound findings could predict successful specimen passage. 相似文献976.
977.
H Sch?cke TM Zollner WD D?cke H Rehwinkel S Jaroch W Skuballa R Neuhaus E May U Zügel K Asadullah 《British journal of pharmacology》2009,158(4):1088-1103
Background and purpose:
Glucocorticoids are highly effective in the therapy of inflammatory diseases. Their value, however, is limited by side effects. The discovery of the molecular mechanisms of the glucocorticoid receptor and the recognition that activation and repression of gene expression could be addressed separately opened the possibility of achieving improved safety profiles by the identification of ligands that predominantly induce repression. Here we report on ZK 245186, a novel, non-steroidal, low-molecular-weight, glucocorticoid receptor-selective agonist for the topical treatment of inflammatory dermatoses.Experimental approach:
Pharmacological properties of ZK 245186 and reference compounds were studied in terms of their potential anti-inflammatory and side effects in functional bioassays in vitro and in rodent models in vivo.Key results:
Anti-inflammatory activity of ZK 245186 was demonstrated in in vitro assays for inhibition of cytokine secretion and T cell proliferation. In vivo, using irritant contact dermatitis and T cell-mediated contact allergy models in mice and rats, ZK 245186 showed anti-inflammatory efficacy after topical application similar to the classical glucocorticoids, mometasone furoate and methylprednisolone aceponate. ZK 245186, however, exhibits a better safety profile with regard to growth inhibition and induction of skin atrophy after long-term topical application, thymocyte apoptosis, hyperglycaemia and hepatic tyrosine aminotransferase activity.Conclusions and implications:
ZK 245186 is a potent anti-inflammatory compound with a lower potential for side effects, compared with classical glucocorticoids. It represents a promising drug candidate and is currently in clinical trials.This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 相似文献978.
Bacterial vaginosis and trichomoniasis vaginitis are risk factors for cuff cellulitis after abdominal hysterectomy 总被引:10,自引:0,他引:10
D E Soper R C Bump W G Hurt 《American journal of obstetrics and gynecology》1990,163(3):1016-21; discussion 1021-3
To assess the relationship between either bacterial vaginosis or trichomoniasis vaginitis and posthysterectomy infection, preoperative evaluation of the vaginal secretions was performed in 161 women undergoing abdominal hysterectomy. Thirty-two patients (19.9%) and 27 patients (16.8%), respectively, met the diagnostic criteria for bacterial vaginosis and trichomoniasis vaginitis. Patients with either bacterial vaginosis or trichomoniasis vaginitis were more likely than control subjects to have cuff cellulitis, cuff abscess, or both (relative risk 3.2, 95% confidence interval 1.5 to 6.7 for bacterial vaginosis; relative risk 3.4, 95% confidence interval 1.6 to 7.1 for trichomoniasis vaginitis). Preoperative vaginitis had no effect with respect to the incidence of postoperative wound infection, urinary tract infection, or intravenous line phlebitis. Bacteroides sp., Peptostreptococcus sp., and/or Gardnerella vaginalis ("bacterial vaginosis organisms") were isolated from the vaginal cuff in the majority of patients with postoperative cuff cellulitis. Bacterial vaginosis and trichomoniasis vaginitis are risk factors for the development of posthysterectomy cuff cellulitis. 相似文献
979.
DR Carvalho MMM Navarro BJAF Martins KEFA Coelho WD Mello RI Takata CE Speck‐Martins 《Clinical genetics》2010,77(2):171-176
Carvalho DR, Navarro MMM, Martins BJAF, Coelho KEFA, Mello WD, Takata RI, Speck‐Martins CE. Mutational screening of ACVR1 gene in Brazilian fibrodysplasia ossificans progressiva patients. Fibrodysplasia ossificans progressiva (FOP) is a severe genetic disorder reported worldwide. A specific heterozygous mutation (c.617G> A; p.R206H) in the activin A type I receptor gene (ACVR1) is regarded as the genetic cause of FOP in all classically affected individuals worldwide. However, a few patients with FOP variants harbor distinct mutations in ACVR1. We screened a group of FOP Brazilian population for mutations in ACVR1. Of 16 patients with a classic FOP phenotype (10 males and 6 females, age range of 3–42 years), all had the classic mutation (p.R206H). One 21‐year‐old woman with a variant FOP phenotype had the previously reported c.983G> A mutation (p.G328E). Our study contributes to the understanding of the predominant FOP phenotype and genotype and suggests that variant FOP phenotypes are associated with specific mutations in ACVR1 gene. 相似文献