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排序方式: 共有652条查询结果,搜索用时 15 毫秒
91.
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Mirbagheri SA Sadeghi A Amouie M Mansouri S Forootan M Rashidi A Abouzari M 《Digestive diseases and sciences》2008,53(10):2621-2626
Gastroesophageal reflux disease (GERD) refractory to conventional medical treatment is frequently associated with gastroparesis, a complex condition with no definitive treatment to date. We first developed a scoring system to assess the severity and frequency of both reflux- and gastroparesis-related symptoms. We then tested, for the first time, the hypothesis that endoscopic pyloric botulinum toxin injection alleviates both of these symptom types. Eleven patients (four males) with GERD (confirmed by esophageal pH monitoring) plus gastroparesis (confirmed by gastric emptying study) underwent toxin injection. Patients had no concomitant disease and were not allowed to use prokinetics before or after treatment. Injection significantly improved both gastroparesis- and reflux-related symptoms in the majority of patients but the duration of symptom relief was relatively short. Responders to treatment had significantly higher total reflux symptom scores (before injection) than nonresponders. All but one of the patients in whom gastroparesis symptoms improved also showed response in reflux symptoms, which supports our hypothesis. We believe that response to toxin injection is a reliable predictor of response to subsequent surgery following the recurrence of symptoms. 相似文献
93.
Davatchi F Jamshidi AR Banihashemi AT Gholami J Forouzanfar MH Akhlaghi M Barghamdi M Noorolahzadeh E Khabazi AR Salesi M Salari AH Karimifar M Essalat-Manesh K Hajialiloo M Soroosh M Farzad F Moussavi HR Samadi F Ghaznavi K Asgharifard H Zangiabadi AH Shahram F Nadji A Akbarian M Gharibdoost F 《The Journal of rheumatology》2008,35(7):1384
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Romagnoli R Baraldi PG Salvador MK Preti D Aghazadeh Tabrizi M Brancale A Fu XH Li J Zhang SZ Hamel E Bortolozzi R Basso G Viola G 《Journal of medicinal chemistry》2012,55(1):475-488
Tubulin, the major structural component of microtubules, is a target for the development of anticancer agents. Two series of 1,5-diaryl substituted 1,2,3,4-tetrazoles were concisely synthesized, using a palladium-catalyzed cross-coupling reaction, and identified as potent antiproliferative agents and novel tubulin polymerization inhibitors that act at the colchicine site. SAR analysis indicated that compounds with a 4-ethoxyphenyl group at the N-1 or C-5 position of the 1,2,3,4-tetrazole ring exhibited maximal activity. Several of these compounds also had potent activity in inhibiting the growth of multidrug resistant cells overexpressing P-glycoprotein. Active compounds induced apoptosis through the mitochondrial pathway with activation of caspase-9 and caspase-3. Furthermore, compound 4l significantly reduced in vivo the growth of the HT-29 xenograft in a nude mouse model, suggesting that 4l is a promising new antimitotic agent with clinical potential. 相似文献
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Baraldi PG Saponaro G Romagnoli R Aghazadeh Tabrizi M Baraldi S Moorman AR Cosconati S Di Maro S Marinelli L Gessi S Merighi S Varani K Borea PA Preti D 《Journal of medicinal chemistry》2012,55(11):5380-5390
A relevant problem of the pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine nucleus, an attractive scaffold for the preparation of adenosine receptor antagonists, is the low water solubility. We originally functionalized the C(5) position with a salifiable 4-pyridylcarbamoyl moiety that conferred good water solubility at low pH (<4.0) but poor solubility at physiologic pH, indicative of the dissociation of the pyridinium species. Here we replaced the pyridin-4-yl moiety with a 1-(substituted)piperidin-4-yl ring to exploit the higher basicity of this nucleus and for the the possibility to generate stable, water-soluble salts. The hydrochloride salt of the 1-(cyclohexylmethyl)piperidin-4-yl derivative (10, K(i)(hA(3)) = 9.7 nM, IC(50)(hA(3)) = 30 nM, K(i)(hA(1)/hA(3)) = 351, K(i)(hA(2A)/hA(3)) > 515, IC(50)(hA(2B)) > 5 μM) showed a solubility of 8 mg/mL at physiological pH and gave a stable aqueous system suitable for intravenous infusion. Molecular modeling studies were helpful in rationalizing the available structure-activity relationships and the selectivity profile of the new ligands. 相似文献
98.
R Romagnoli PG Baraldi MD Carrion CL Cara O Cruz-Lopez MK Salvador D Preti MA Tabrizi AR Moorman F Vincenzi PA Borea K Varani 《Journal of medicinal chemistry》2012,55(17):7719-7735
We have recently reported a detailed structure-activity relationship study around a wide series of 2-amino-3-(4-chlorobenzoyl)-4-[(4-arylpiperazin-1-yl)methyl]thiophene derivatives as potent allosteric enhancers of the A(1) adenosine receptor. In the current study, we have continued to explore the potential of these molecules by synthesizing of a novel series of analogues that share a common 2-amino-3-(4-chlorobenzoyl)thiophene nucleus. Modifications were focused on varying the nature and the position of electron-withdrawing or electron-releasing groups on the phenyl of an arylpiperazine moiety attached at the 4-position of the thiophene ring by a methylene chain, combined with the presence of small alkyl groups (methyl or ethyl), bromine, or aryl moieties at the thiophene C-5 position. In this series of compounds, substitution at the 5-position had a fundamental effect on activity, with the 5-aryl group contributing additively to the allosteric enhancer activity. The thiophene C-5 aryl derivatives 4ad, 4ak, and 4al were the most active compounds in binding and functional experiments. 相似文献
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Maryam SAHEBARI Mojgan AFKHAMIZADEH Kamila HASHEMZADEH Masoud PEZESHKI RAD 《International journal of rheumatic diseases》2010,13(2):175-179
Systemic lupus erythematosus (SLE) is an autoimmune disease in which organs undergo damage. Hypoparathyroidism is a rare disease, which presents in two forms: hereditary and acquired. Cases of hypoparathyroidism and SLE rarely co‐exist. Only six cases have been reported; five of them first presented with lupus and then hypoparathyroidism or simultaneously. We present here developing lupus disease in a woman who had idiopathic hypoparathyroidism. According to increasing data about the autoimmune origin of idiopathic hypoparathyroidism, these case reports suggest that there may be an autoimmune process linking these diseases. 相似文献