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排序方式: 共有246条查询结果,搜索用时 15 毫秒
91.
92.
Perić M Fajdetić A Rupčić R Alihodžić S Ziher D Bukvić Krajačić M Smith KS Ivezić-Schönfeld Z Padovan J Landek G Jelić D Hutinec A Mesić M Ager A Ellis WY Milhous WK Ohrt C Spaventi R 《Journal of medicinal chemistry》2012,55(3):1389-1401
Novel classes of antimalarial drugs are needed due to emerging drug resistance. Azithromycin, the first macrolide investigated for malaria treatment and prophylaxis, failed as a single agent and thus novel analogues were envisaged as the next generation with improved activity. We synthesized 42 new 9a-N substituted 15-membered azalides with amide and amine functionalities via simple and inexpensive chemical procedures using easily available building blocks. These compounds exhibited marked advances over azithromycin in vitro in terms of potency against Plasmodium falciparum (over 100-fold) and high selectivity for the parasite and were characterized by moderate oral bioavailability in vivo. Two amines and one amide derivative showed improved in vivo potency in comparison to azithromycin when tested in a mouse efficacy model. Results obtained for compound 6u, including improved in vitro potency, good pharmacokinetic parameters, and in vivo efficacy higher than azithromycin and comparable to chloroquine, warrant its further development for malaria treatment and prophylaxis. 相似文献
93.
We evaluated whether the presence of polycystic ovaries in adolescent girls as a cause of oligomenorrhoea and amenorrhoea would pose any protective effect against osteoporosis or low bone mineral density (BMD) compared with girls having similar menstrual dysfunction but normal ovaries. A cross-sectional observational study was done in consecutive girls, aged between 16 and 19 years, presenting to the adolescent gynaecology clinic with oligomenorrhoea or amenorrhoea. All patients underwent full hormonal profile assessment, pelvic ultrasound for ovarian morphology, bio-impedance estimation of body fat, and dual-energy X-ray absorptiometry and quantitative peripheral computed tomography scans to determine BMD in axial and appendicular skeletal sites. Polycystic ovaries were diagnosed according to ultrasound morphology. These were then compared with an age-matched eumenorrhoeic control group that had undergone the same evaluation. Of 45 patients with oligomenorrhoea or amenorrhoea, 14 (31%) were diagnosed to have polycystic ovaries, while the other 31 had normal ovaries. The control group consisted of 45 age-matched eumenorrhoeic girls. The group with normal ovaries had lower BMD at the lumbar spine and hip, as well as lower total tibial volumetric BMD, than the eumenorrhoeic controls, but there were no significant differences between the group with polycystic ovaries and eumenorrhoeic controls. We conclude that adolescents with oligomenorrhoea and amenorrhoea with normal ovaries had lower BMD than eumenorrhoeic ones, but those with polycystic ovaries had BMD values comparable to those of eumenorrhoeic controls despite their menstrual dysfunction. 相似文献
94.
Gbotosho GO Ogundahunsi OA Happi CT Kyle DE Gerena L Milhous WK Sowunmi A Oduola AM Salako LA 《Annals of tropical medicine and parasitology》2006,100(7):571-578
An in-vitro model based on the semi-automated microdilution technique has been developed for selecting compounds that might be used clinically for the reversal of chloroquine resistance. This was used initially to test the susceptibility of Plasmodium falciparum clone W2 to chloroquine (CQ). The model was then employed to investigate the effects of each of four resistance-reversing agents (verapamil, desipramine, chlorpheniramine and promethazine, at 1 microM) on this parasite's susceptibility to CQ, with and without alpha(1)-acid glycoprotein (AGP), at a patho-physiological concentration (1.25 g/litre), in the culture medium. In the absence of AGP, each of the resistance-reversing agents reduced the median inhibitory concentrations of CQ by 82%-97%, from a baseline value of about 94 ng/ml. In the presence of AGP, however, most of the resistance-reversing agents had much less effect. There appears to be competitive interaction between CQ, the resistance-reversing agents and AGP. The binding kinetics between CQ, resistance-reversing agents, AGP and other plasma proteins will clearly need to elucidated if clinically effective resistance-reversing agents are to be selected in vitro. 相似文献
95.
96.
朝藿素B和朝藿素C的结构 总被引:3,自引:0,他引:3
从朝鲜淫羊藿(Epeimedium koreanum Nadai)地上部分中分离得到二个新黄酮成分:朝藿素B(epimedokoreanin B)(Ix)和朝藿素C(epimedokoreanin C)(XV),经光谱分析证明,朝藿素B(IX)的结构为5,7,3`,4`-tetrahydroxyl-8,5`,-diprenylflavone;朝藿素c(xv)的结构为5,7,31`,7`-tetrahydroxyl-8-prenyl-2{[2`-(l-hydroxyl-l-methylethyl)-2`,3`-dihydrobenzofuran]-5`-yl}-chromone. 相似文献
97.
98.
P W Kelley E T Takafuji H Wiener W Milhous R Miller N J Thompson P Schantz R N Miller 《Military medicine》1989,154(2):55-59
During 1983, a multinational military intervention took place on Grenada. After deployment, troops from several U.S. Army units noted signs and symptoms consistent with soil-transmitted helminthic infection. Of 684 soldiers screened five to seven weeks post-deployment, over 20% reported abdominal pain and/or diarrhea during or after the action. Eosinophilia of at least 10% was observed in 119 (22.5%) of 529 soldiers evaluated further; eosinophilia of 5-9% was documented in another 126 (23.8%) of the 529 soldiers. Stool examinations confirmed hookworm infection in 35 soldiers. One case of strongyloidiasis was also documented. Infection was attributed to ground exposure near homes with compromised sanitation. Units that joined the operation after the initial assault phase were at low risk of hookworm infection. 相似文献
99.
J Verspeelt P De Locht WK Amery 《Cephalalgia : an international journal of headache》1996,16(5):328-336
A comparative post-marketing surveillance study of the safety and efficacy of flunarizine and propranolol in the treatment of migraine was carried out. General practitioners in Belgium and the Netherlands each recruited patients for whom they would prescribe one of the study medications in the normal course of their treatment and recorded all medical events on follow-up forms for up to 8 months. A total of 1601 migraine patients were enrolled; 838 in the flunarizine cohort and 763 in the propranolol cohort. Propranolol was somewhat better than flunarizine in reducing the severity of migraine attacks, although this may have been due to a selection bias. Discontinuations of therapy due to events considered likely to be treatment-related were mostly due to the recognized side effects of the two drugs. As regards the occurrence of depressions, a total of 58 patients had depressive events, 34 in the flunarizine cohort and 24 in the propranolol cohort. Whereas migraine itself appears to be associated with an increased risk of depression, the number of previous migraine treatments was shown to be an additional risk factor for the development of depression in patients receiving flunarizine as was a history of depression. Overall, there was no appreciable difference in the risk/benefit ratio between flunarizine and propranolol. 相似文献
100.
Abstract Bronchiectasis is defined in current medical parlance as the abnormal and permanent dilatation of one or more bronchi, and in clinical practice, the condition is often characterized by features of chronic bronchial infection. Apart from occurring as a primary lung disease, bronchiectasis is a major component of two other disease entities, cystic fibrosis and diffuse panbronchiolitis. Although the three conditions have distinctly different underlying causes, they share the similarity of a predominantly neutrophilic airways inflammation, and the persistent bronchial infection by bacteria, in particular Pseudotnonas aeruginosa . Hence, new knowledge in one disease may be explored and applied in the others. 相似文献