Venticute in Patients With Pneumonia or Aspiration of Gastric Contents Leading to Intubation, Ventilation, and Severe Oxygenation Impairment: A Randomized, Multinational, Multicenter, Parallel Group, Double Blind, Control Group Study

Study to demonstrate that administration of Venticute increases survival of patients with pneumonia or aspiration of gastric contents leading to intubation, mechanical ventilation, and severe oxygenation impairment.

开始日期2003-11-01

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

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185

项与 Lusupultide 相关的文献（医药）

2024-12-01·Journal of Ethnopharmacology

Novel insights into the molecular mechanisms underlying anti-nociceptive effect of myricitrin against reserpine-induced fibromyalgia model in rats: Implication of SIRT1 and miRNAs

Article

作者: Harras, Marwa F ; El-Said, Nermin T ; Zaky, Heba S ; Allam, Albatoul ; Farag, Fatma Sayed Abdel-Aal ; Aboutaleb, Amany S ; Abdel-Sattar, Somaia A ; Ahmed, Hebatalla I ; Abd El-Mordy, Fatma Mohamed

ETHNOPHARMACOLOGICAL RELEVANCEManilkara zapota (L.) P. Royen, also termed sapodilla or chikoo, is a significant plant in ethnomedicine because of its long history of traditional medical applications. In diverse cultures, sapodilla is believed to protect against oxidative stress, inflammation, and some chronic diseases because of its high antioxidant content. The naturally occurring antioxidant myricitrin (MYR) flavonoid is primarily found in the leaves and other plant parts of sapodilla and it is well-known for having therapeutic qualities and possible health advantages.AIM OF THE STUDYTo appraise the possible impact of MYR on a rat model of reserpine-induced fibromyalgia (FM) and explore its mechanism of action.MATERIALS AND METHODSIsolation and identification of MYR with more than 99% purity from Manilkara zapota leaves were primarily done and confirmed through chromatographic and spectrophotometric techniques. To develop FM model, reserpine (RSP) was injected daily (1 mg/kg, s.c.) for three successive days. Then, MYR (10 mg/kg, i.p.) and pregabalin (PGB, 30 mg/kg, p.o.) were given daily for another five days. Behavioral changes were assessed through open field test (OFT), hot plate test, and forced swimming test (FST). Further analyses of different brain parameters and signaling pathways were performed to assess monoamines levels, oxidative stress, inflammatory response, apoptotic changes as well as silent information regulator 1 (SIRT1) and micro RNAs (miRNAs) expressions.RESULTSFrom High-Performance Liquid Chromatography (HPLC) analysis, the methanol extract of sapodilla leaves contains 166.17 μg/ml of MYR. Results of behavioral tests showed a significant improvement in RSP-induced nociceptive stimulation, reduced locomotion and exploration and depressive-like behavior by MYR. Biochemical analyses showed that MYR significantly ameliorated the RSP-induced imbalance in brain monoamine neurotransmitters. In addition, MYR significantly attenuated oxidative stress elicited by RSP via up-regulating nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expressions, enhancing superoxide dismutase (SOD) and catalase (CAT) activities, and reducing malondialdehyde (MDA) content in brain. The RSP-provoked inflammatory response was also diminished by MYR treatment as shown by a significant decreased NOD-like receptor protein 3 (NLRP3) inflammasome expression along with reduced levels of interleukin 1 beta (IL-1β) and nuclear factor-κB (NF-κB). Furthermore, the anti-apoptotic activity of MYR was demonstrated by a marked rise in Bcl-2-associated X protein (BAX)/B cell lymphoma-2 (Bcl-2) ratio by lowering Bcl-2 while increasing BAX levels. In addition, MYR treatment significantly boosted the expression of SIRT1 deacetylase in RSP-treated animals. Interestingly, molecular docking showed the ability of MYR to form a stable complex in the binding site of SIRT1. Regarding miRNAs, MYR effectively ameliorated RSP-induced changes in miR-320 and miR-107 gene expressions.CONCLUSIONOur findings afford new insights into the anti-nociceptive profile of MYR in the RSP-induced FM model in rats. The underlying mechanisms involved direct binding and activation of SIRT1 to influence different signaling cascades, including Nrf2 and NF-κB/NLRP3 together with modulation of miRNAs. However, more in-depth studies are needed before proposing MYR as a new clinically relevant drug in the management of FM.

2024-11-01·Journal of Chromatography A

Expanding cyclodextrin use in normal phase and super/subcritical fluid chromatographic modes for the chiral separation of 1,4-dihydropyridines

Article

作者: Salehi, Reza ; Koçak Aslan, Ebru ; Sajeevan J, Siddharth Jaya ; Armstrong, Daniel W ; Armstrong, Daniel W. ; Gündüz, Miyase Gözde ; Burk, Ryan Jacob

Cyclodextrin-based stationary phases are important chiral selectors in liquid chromatography. These chiral selectors are most commonly used in the reversed-phase mode because native cyclodextrin assumes a torus conformation with a hydrophobic cavity, facilitating inclusion complexation in aqueous environments. However, the value of native and aliphatic-derivatized cyclodextrins in other modes, such as the normal phase liquid chromatography (NPLC) or super/subcritical fluid chromatography (SFC), remains unexplored. In this work, we report chiral separations of pharmaceutically relevant compounds with the 1,4-dihydropyridine (DHP) scaffold on a 2-hydroxypropyl-β-cyclodextrin (CD-RSP) stationary phase in NPLC and SFC modes. Although CD-RSP is conventionally considered only effective in the reversed-phase mode, we show that these compounds tend to separate better in other modes. This is particularly apparent for analytes with hydrogen-bonding moieties. We propose that the separation mechanism primarily depends on external adsorption rather than inclusion complexation. The negligible impact of a complexation-competitive additive on retention in non-aqueous modes further supports this claim. Additionally, van Deemter analysis demonstrated the efficiency and environmental benefit of using this stationary phase in the SFC mode, further highlighting the promise of aliphatic derivatized cyclodextrin stationary phases for greener separations.

2024-10-14·ACS Biomaterials Science & Engineering

Influence of Initial Secondary Structure on Conformation and Mechanical Properties of Spider Silk Protein Gels

Article

作者: Suzuki, Yu ; Satoh, Ryo ; Sato, Takehiro K. ; Higashi, Takanori ; Okamura, Hideyasu ; Morinaga, Takashi

Recombinant spider silk protein (RSP) is a promising biomaterial for developing high-performance materials independent of fossil fuels. In this study, we investigated the influence of the initial secondary structure of RSPs on the properties of RSP-based hydrogels. By altering the initial structure of RSP to β-sheets (β-RSP), α-helices (α-RSP), and random coils (rc-RSP) through solvent treatment, we compared the structures and mechanical properties of the resulting gels. Solid-state NMR revealed a β-sheet-rich structure in all gels, with the α-RSP gel exhibiting significantly higher strength and Young's modulus compared to the rc-RSP gel. X-ray diffraction revealed that the α-RSP gel had a unique crystalline structure, distinguishing it from the β-RSP and rc-RSP gels. The different initial secondary structures possibly lead to variations in the crystalline and network structures of the molecular chains within the gels, explaining the superior mechanical properties observed in the α-RSP gels.

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外链

KEGG	Wiki	ATC	Drug Bank
D08943	-	-	-

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适应症	最高研发状态	国家/地区	公司	日期
成人呼吸窘迫综合征	临床3期	大洋洲	Nycomed GmbH	-
成人呼吸窘迫综合征	临床3期	以色列	Nycomed GmbH	-
成人呼吸窘迫综合征	临床3期	加拿大	Nycomed GmbH	-
成人呼吸窘迫综合征	临床3期	南非	Nycomed GmbH	-
成人呼吸窘迫综合征	临床3期	美国	Nycomed GmbH	-
成人呼吸窘迫综合征	临床3期	-	Johnson & Johnson	-
成人呼吸窘迫综合征	临床3期	南美洲	Nycomed GmbH	-
成人呼吸窘迫综合征	临床3期	欧盟	Nycomed GmbH	-
成人呼吸窘迫综合征	临床3期	瑞士	Nycomed GmbH	-
成人呼吸窘迫综合征	临床3期	俄罗斯	Nycomed GmbH	-

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ASN2012	N/A	APC \| sEPCR \| sTM ... 更多	-	Recombinant Protein C	鏇窪鏇網製獵顧築鬱淵(鹽遞夢獵廠衊選壓鹽鬱) = increased 糧顧鹹獵繭鑰觸築築夢 (鏇簾觸壓鏇製選膚夢衊 ) 更多	积极	2012-10-30
				Recombinant Protein C