For post-Cesarean analgesia, the investigators will compare the efficacy of single-shot epidural preservative free morphine with a continuous epidural fentanyl infusion. The investigators will be comparing the patient's pain level and satisfaction with the two techniques, as well as the side effects that the patients experience, such as itching, nausea, back pain and respiratory depression.

开始日期2011-01-01

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100 项与甲磺酸阿曲沙星相关的临床结果

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100 项与甲磺酸阿曲沙星相关的转化医学

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100 项与甲磺酸阿曲沙星相关的专利（医药）

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项与甲磺酸阿曲沙星相关的文献（医药）

2019-12-02·Molecular Pharmaceutics2区 · 医学

Optimizing Lysosomal Activation of Antibody–Drug Conjugates (ADCs) by Incorporation of Novel Cleavable Dipeptide Linkers

2区 · 医学

Article

作者: Miller, Michael L. ; Reid, Emily E. ; Maloney, Erin K. ; Archer, Katie E. ; Chari, Ravi V. J. ; Wilhelm, Alan J. ; Keating, Thomas A. ; Harris, Luke ; Singh, Rajeeva ; Salomon, Paulin L.

Although peptide linkers are used in multiple clinical-stage ADCs, there are only few reports on optimizing peptide linkers for efficient lysosomal proteolysis and for stability in circulation. We screened multiple dipeptide linkers for efficiency of proteolysis and compared them to the dipeptide linkers currently being evaluated in the clinic: Val-Cit, Val-Ala, and Ala-Ala. Lead dipeptide linkers selected from the initial screen were incorporated into ADCs with indolinobenzodiazepine dimer (IGN) payloads to evaluate cellular processing, in vitro cytotoxic activity, plasma stability, and in vivo efficacy. ADCs with several dipeptide linkers bearing l-amino acids showed faster lysosomal processing in target cancer cells compared to the l-Ala-l-Ala linked ADC. These variances in linker processing rates did not result in different in vitro and in vivo activities among peptide linker ADCs, presumably due to accumulation of threshold cytotoxic catabolite levels for ADCs of several peptide linkers in the cell lines and xenografts tested. ADCs with l-amino acid dipeptide linkers exhibited superior in vitro cytotoxic potencies in multiple cell lines compared to an ADC with a d-Ala-d-Ala dipeptide linker and an ADC with a noncleavable linker. This work adds to the toolbox of stable, lysosomally cleavable peptide linkers for ADCs.

2018-02-01·Biochemistry (Moscow)4区 · 生物学

2,5-Diketopiperazines: A New Class of Poly(ADP-ribose)polymerase Inhibitors

4区 · 生物学

Article

作者: V. K. Švedas ; D. K. Nilov ; A. L. Zakharenko ; I. V. Gushchina ; M. V. Sukhanova ; O. I. Lavrik ; K. I. Yashina

We show for the first time that natural 2,5-diketopiperazines (cyclic dipeptides) can suppress the activity of the important anticancer target poly(ADP-ribose)polymerase (PARP). Cyclo(L-Ala-L-Ala) and cyclo(L-Ala-D-Ala) can interact with the key residues of the PARP-1 active site, as demonstrated using docking and molecular dynamics simulations. One of the amide groups of cyclo(L-Ala-L-Ala) and cyclo(L-Ala-D-Ala) forms hydrogen bonds with the Gly863 residue, while the second amide group can form a hydrogen bond with the catalytic residue Glu988, and the side chain can make a hydrophobic contact with Ala898. Newly identified diketopiperazine inhibitors are promising basic structures for the design of more effective inhibitors of PARP family enzymes. The piperazine core with two chiral centers provides many opportunities for structural optimization.

2016-07-01·Microbiology4区 · 生物学

Secretion of d-alanine by Escherichia coli

4区 · 生物学

Article

作者: Isogai, Emiko ; Ando, Tasuke ; Yoneyama, Hiroshi ; Katsube, Satoshi ; Sato, Kazuki

Escherichia coli has an l-alanine export system that protects the cells from toxic accumulation of intracellular l-alanine in the presence of l-alanyl-l-alanine (l-Ala-l-Ala). When a DadA-deficient strain was incubated with 6.0 mM l-Ala-l-Ala, we detected l-alanine and d-alanine using high-performance liquid chromatography (HPLC) analysis at a level of 7.0 mM and 3.0 mM, respectively, after 48 h incubation. Treatment of the culture supernatant with d-amino acid oxidase resulted in the disappearance of a signal corresponding to d-alanine. Additionally, the culture supernatant enabled a d-alanine auxotroph to grow without d-alanine supplementation, confirming that the signal detected by HPLC was authentic d-alanine. Upon introduction of an expression vector harbouring the alanine racemase genes, alr or dadX, the extracellular level of d-alanine increased to 11.5 mM and 8.5 mM, respectively, under similar conditions, suggesting that increased metabolic flow from l-alanine to d-alanine enhanced d-alanine secretion. When high-density DadA-deficient cells preloaded with l-Ala-l-Ala were treated with 20 µM carbonyl cyanide m-chlorophenyl hydrazone (CCCP), secretion of both l-alanine and d-alanine was enhanced ~twofold compared with that in cells without CCCP treatment. In contrast, the ATPase inhibitor dicyclohexylcarbodiimide did not exert such an effect on the l-alanine and d-alanine secretion. Furthermore, inverted membrane vesicles prepared from DadA-deficient cells lacking the l-alanine exporter AlaE accumulated [3H]D-alanine in an energy-dependent manner. This energy-dependent accumulation of [3H]D-alanine was strongly inhibited by CCCP. These results indicate that E. coli has a transport system(s) that exports d-alanine and that this function is most likely modulated by proton electrochemical potential.

100 项与甲磺酸阿曲沙星相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D02470	甲磺酸阿曲沙星	J01MA13	DB09335

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01362998 (CTgov)	N/A	镇痛	2	Preservative free morphine (Preservative Free Morphine)	廠積顧範衊齋繭壓簾選(醖鏇製憲顧選齋製襯艱) = 餘築憲齋觸廠艱齋顧簾膚簾構範夢壓艱餘糧願 (蓋膚築顧艱願鹹夢積築, 構鹹願獵網齋廠夢艱鹹 ~ 範觸鹽窪選鹽選廠簾顧) 更多	-	2022-11-14
				Fentanyl (Fentanyl Infusion)	鏇製鹹範範鬱壓願鹽衊(鹽淵糧憲簾鏇艱艱選獵) = 製製築鹽艱網憲鑰廠淵鏇積衊膚鹹簾鏇蓋觸構 (窪獵獵鏇範鹽積醖鹽顧, 衊積繭鏇範齋積襯膚壓 ~ 願餘蓋膚衊鏇積齋蓋構) 更多