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991.
992.
Amartya Basu Maksim Chudayeu Paula de F. de Moraes Tanaji T. Talele Paulo R. R. Costa Neerja Kaushik‐Basu 《Chemical biology & drug design》2013,81(5):607-614
Coumarins and coumestans represent an important family of compounds with diverse pharmacological properties. We recently identified coumestans as novel inhibitors of hepatitis C virus NS5B polymerase and predicted their binding in thumb pocket‐1 (TP‐1) of NS5B. As the coumarins are structurally related to coumestans by virtue of their common A‐ and B‐rings, we postulated them to also exhibit similar binding interaction with NS5B and inhibit its polymerase function. We therefore investigated 24 coumarin and neoflavone derivatives as candidate NS5B inhibitors and identified 14 compounds inhibiting NS5B polymerase activity with IC50 values between 17 and 63 μm . Of these, the newly synthesized 6,8‐diallyl‐5,7‐dihydroxycoumarin ( 8a ) was produced in three steps in high chemical yield from floroglucinol and found to be the most potent of this series, exhibiting activity similar to the reference coumestan LQB‐ 34 . The binding site of 8a was mapped to TP‐1 of NS5B by counter screening against P495L NS5B mutant, employed as a screen for TP‐1 site binders. NS5B‐TP‐1‐ 8a interaction map provided insight into 8a binding and offered clues for future SAR optimization. 相似文献
993.
Kelvin P. Jordan Richard A. Hayward Milisa Blagojevic‐Bucknall Peter Croft 《International journal of cancer. Journal international du cancer》2013,133(3):713-720
Musculoskeletal pain has been linked with subsequent cancer. The objective was to investigate associations between pain sites and specific cancers, and investigate the hypothesis that musculoskeletal pain is an early marker, rather than cause, of cancer. This was a cohort study in the General Practice Research Database. From a cohort of 46,656 people aged ≥50 years with a recorded musculoskeletal problem in 1996 but not during the previous 2 years, patients with a new consultation for back, neck, shoulder or hip pain in 1996 were selected and compared with 39,253 persons who had had no musculoskeletal consultation between 1994 and 1996. Outcome was incidence of prostate, breast, lung and colorectal cancer up to 10 years after baseline consultation. Strongest associations with prostate cancer were in the first year of follow‐up for males consulting initially with back (adjusted hazard ratio 5.42; 95% CI 3.31, 8.88), hip (6.08; 2.87, 12.85) or neck problems (3.46; 1.58, 7.58). These associations remained for back and neck problems over 10 years. Significant associations existed with breast cancer up to 5 years after consultation in females with hip problems, and with breast and lung cancer in the first year after presentation with back problems. Previously observed links between pain and cancer reflect specific associations between pain sites and certain cancers. One explanation is liability for bony metastases from primary sites, and that pain represents a potential early marker of cancer. However, older patients with uncomplicated musculoskeletal pain seen in clinical practice have a low absolute excess cancer risk. 相似文献
994.
Ximena Terra PhD Teresa Auguet MD PhD Zaida Agüera MSc Isabel Maria Quesada Josep Maria Orellana‐Gavaldà PhD Carmen Aguilar PhD Susana Jiménez‐Murcia PhD Alba Berlanga MSc Esther Guiu‐Jurado MSc José Manuel Menchón MD Fernando Fernández‐Aranda PhD Cristóbal Richart MD PhD 《The International journal of eating disorders》2013,46(8):855-861
995.
Jung Yeon Chin M.D. Jeong Eun Yi M.D. Ho‐Joong Youn M.D. Ph.D. 《Echocardiography (Mount Kisco, N.Y.)》2013,30(9):E269-E273
Cardiac involvement in Churg–Strauss syndrome (CSS) is a major cause of mortality. Here we report a case of a 75‐year‐old woman with eosinophilic endomyocarditis due to CSS. An electrocardiogram showed intraventricular conduction delay, and echocardiography showed an impaired relaxation pattern and biventricular apical thickening. Magnetic resonance imaging revealed subendocardial delayed enhancement with biventricular apical thrombi. Endomyocardial biopsy showed perivascular eosinophilic infiltration. Despite resolution of the hypereosinophilia after steroid therapy, her left ventricular (LV) diastolic function worsened into a restrictive pattern and she died with a ventricular escape rhythm on her 14th day in the hospital. This case is unusual in that there was rapid progression of the LV diastolic dysfunction and conduction disturbance due to CSS. 相似文献
996.
997.
The experiences of myocardial infarction patients readmitted within six months of primary percutaneous coronary intervention 下载免费PDF全文
Heather Iles‐Smith RGN MSc PhD Christi Deaton PhD RN FAHA FESC FAAN Malcolm Campbell BSc MSc PhD Catherine Mercer BSc Linda McGowan RN RM BSc MSc PhD 《Journal of clinical nursing》2017,26(21-22):3511-3518
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999.
Geltrude Mingrone Lidia Castagneto‐Gissey Katherine Macé 《British journal of clinical pharmacology》2013,75(3):671-676
Even‐number, medium‐chain dicarboxylic acids (DAs), naturally occurring in higher plants, are a promising alternative energy substrate. Unlike the homologous fatty acids, DAs are soluble in water as salts. They are β‐oxidized, providing acetyl‐CoA and succinyl‐CoA, the latter being an intermediate of the tricarboxylic acid cycle. Sebacic acid and dodecanedioic acid, DAs with 10 and 12 carbon atoms respectively, provide 6.6 and 7.2 kcal g−1 each; therefore, their energy density is intermediate between glucose and fatty acids. Dicarboxylic acids have been proved to be safe in both experimental animals and humans, and their use has recently been proposed in diabetes. Studies in animals and humans with type 2 diabetes showed that oral administration of sebacic acid improved glycaemic control, probably by enhancing insulin sensitivity, and reduced hepatic gluconeogenesis and glucose output. Moreover, dodecanedioic acid intake reduced muscle fatigue during exercise in subjects with type 2 diabetes, suggesting an improvement of energy utilization and ‘metabolic flexibility’. In this article, we review the natural sources of DAs, their fate in animals and humans and their effect in improving glucose metabolism in type 2 diabetes. 相似文献
1000.