This study is being done to evaluate cutaneous nerve biopsies from patients with refractory gastrointestinal motility disorders. The purpose of the study is to evaluate skin biopsies for signs of small fiber neuropathy in GI dysmotility patients, which may provide a better understanding of the underlying pathology of their condition. Specifically, identifying any small fiber neuropathy that may exist in the peripheral nervous system may help us to better understand the mechanism of presumed enteric neuropathy that may be involved in causing GI dysmotility.

开始日期2023-12-22

申办/合作机构

The Johns Hopkins University

ChiCTR1800015099 / RecruitingIIT

The Effects of Single-Dose Etomidate Versus Propofol on Cortisol Levels in Elderly Patients Undergoing Gastrointestinal Tumor Surgery

开始日期2018-03-07

申办/合作机构-

JPRN-UMIN000030725 / Recruiting临床2期IIT

Randomized study evaluating antiperistaltic effect of mildly cold water sprayed onto the gastrointestinal mucosa for colonoscopy - Randomized study evaluating antiperistaltic effect of mildly cold water sprayed onto the gastrointestinal mucosa for colonoscopy

开始日期2018-01-04

申办/合作机构-

100 项与胃肠痉挛相关的临床结果

登录后查看更多信息

100 项与胃肠痉挛相关的转化医学

登录后查看更多信息

0 项与胃肠痉挛相关的专利（医药）

登录后查看更多信息

454

项与胃肠痉挛相关的文献（医药）

2024-07-01·Bioorganic Chemistry

Novel trifluoromethyl ketone derivatives as oral cPLA2/COX-2 dual inhibitors for resolution of inflammation in rheumatoid arthritis

Article

作者: Cai, Nan ; Zhou, Yuhan ; Gao, Xiang ; Li, Wenjing ; Qu, Jingping ; Yang, Li ; Zhao, Jinfeng

Thirty-five trifluoromethyl hydrazones and seventeen trifluoromethyl oxime esters were designed and synthesized via molecular hybridization. All the target compounds were initially screened for in vitro anti-inflammatory activity by assessing their inhibitory effect on NO release in LPS-stimulated RAW264.7 cells, and the optimal compound was finally identified as 2-(3-Methoxyphenyl)-N'-((6Z,9Z,12Z,15Z)-1,1,1-trifluorohenicosa-6,9,12,15-tetraen-2-ylidene)acetohydrazide (F26, IC₅₀ = 4.55 ± 0.92 μM) with no cytotoxicity. Moreover, F26 potently reduced the production of PGE₂ in LPS-stimulated RAW264.7 cells compared to indomethacin. The interaction of F26 with COX-2 and cPLA₂ was directly verified by the CETSA technique. F26 was found to modulate the phosphorylation levels of p38 MAPK and NF-κB p65, as well as the protein expression of IκB, cPLA₂, COX-2, and iNOS in LPS-stimulated rat peritoneal macrophages. Additionally, F26 was observed to prevent the nuclear translocation of NF-κB p65 in LPS-stimulated rat peritoneal macrophages by immunofluorescence localization. Therefore, the aforementioned in vitro experiments demonstrated that F26 blocked the p38 MAPK and NF-κB pathways by binding to COX-2 and cPLA₂. In the adjuvant-induced arthritis model, F26 demonstrated a significant effect in preventing arthritis symptoms and inflammatory status in rats, exerting an immunomodulatory role by regulating the homeostasis between Th17 and Treg through inhibition of the p38 MAPK/cPLA₂/COX-2/PGE₂ and NF-κB pathways. Encouragingly, F26 caused less acute ulcerogenicity in rats at a dose of 50 mg/kg compared to indomethacin. Overall, F26 is a promising candidate worthy of further investigation for treating inflammation and associated pain with lesser gastrointestinal irritation, as well as other symptoms in which cPLA₂ and COX-2 are implicated in the pathophysiology.

2024-06-01·Acta Pharmaceutica

Lipid-based systems with precipitation inhibitors as formulation approach to improve the drug bioavailability and/or lower its dose: a review

Review

作者: Gašperlin, Mirjana ; Pobirk, Alenka Zvonar ; Kovačević, Mila

AbstractLipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly water-soluble drugs. By applying the “spring and parachute” strategy in designing supersaturable SMEDDS, it is possible to maintain the drug in the supersaturated state long enough to allow absorption of the complete dose, thus improving the drug’s bio-availability. As such an approach allows the incorporation of larger amounts of the drug in equal or even lower volumes of SMEDDS, it also enables the production of smaller final dosage forms as well as decreased gastrointestinal irritation, being of particular importance when formulating dosage forms for children or the elderly. In this review, the technological approaches used to prolong the drug supersaturation are discussed regarding the type and concentration of polymers used in liquid and solid SMEDDS formulation. The addition of hypromellose derivatives, vinyl polymers, polyethylene glycol, polyoxyethylene, or polymetacrylate copolymers proved to be effective in inhibiting drug precipitation. Regarding the available literature, hypromellose has been the most commonly used polymeric precipitation inhibitor, added in a concentration of 5 % (m/m). However, the inhibiting ability is mainly governed not only by the physicochemical properties of the polymer but also by the API, therefore the choice of optimal precipitation inhibitor is recommended to be evaluated on an individual basis.

2024-06-01·Biomedicine & Pharmacotherapy

Multiple drug-delivery strategies to enhance the pharmacological and toxicological properties of Mefenamic acid

Article

作者: Rimoli, Maria Grazia ; Rolando, Barbara ; Dixon, Emily ; Axioti, Eleni ; Moloney, Cara ; Cuzzucoli Crucitti, Valentina ; Cristiano, Claudia ; Liguori, Fabrizio Maria ; Russo, Roberto ; Cuozzo, Mariarosaria ; Schiano, Marica Erminia ; Sodano, Federica ; Jacob, Philippa L ; Taresco, Vincenzo ; Cavanagh, Robert J

OBJECTIVETo improve the biological and toxicological properties of Mefenamic acid (MA), the galactosylated prodrug of MA named MefeGAL was included in polymeric solid dispersions (PSs) composed of poly(glycerol adipate) (PGA) and Pluronic® F68 (MefeGAL-PS). MefeGAL-PS was compared with polymeric solid formulations of MA (MA-PS) or a mixture of equal ratio of MefeGAL/MA (Mix-PS).METHODSThe in vitro and in vivo pharmacological and toxicological profiles of PSs have been investigated. In detail, we evaluated the anti-inflammatory (carrageenan-induced paw edema test), analgesic (acetic acid-induced writhing test) and ulcerogenic activity in mice after oral treatment. Additionally, the antiproliferative activity of PSs was assessed on in vitro models of colorectal and non-small cell lung cancer.RESULTSWhen the PSs were resuspended in water, MefeGAL's, MA's and their mixture's apparent solubilities improved due to the interaction with the polymeric formulation. By comparing the in-vivo biological performance of MefeGAL-PS with that of MA, MefeGAL and MA-PS, it was seen that MefeGAL-PS exhibited the same sustained and delayed analgesic and anti-inflammatory profile as MefeGAL but did not cause gastrointestinal irritation. The pharmacological effect of Mix-PS was present from the first hours after administration, lasting about 44 hours with only slight gastric mucosa irritation. In-vitro evaluation indicated that Mix-PS had statistically significant higher cytotoxicity than MA-PS and MefeGAL-PS.CONCLUSIONSThese preliminary data are promising evidence that the galactosylated prodrug approach in tandem with a polymer-drug solid dispersion formulation strategy could represent a new drug delivery route to improve the solubility and biological activity of NSAIDs.