The purpose of this study is to assess the way the body absorbs, distributes, breaks down and eliminates radioactive BMS-986278 as well as the safety and tolerability of BMS-986278 in healthy male participants.

Start Date15 Oct 2020

Sponsor / Collaborator

Bristol Myers Squibb Co.

NCT01656057 / CompletedNot ApplicableIIT

The Impact of Gall Bladder Emptying and Bile Acids on the Human GLP-1-secretion

The last couple of years it has been shown that bile acids not only acts as simple emulsifiers of fat, but constitutes a complex metabolic integrator which not only have an influence on fat digestion and lipid metabolism, but also modulates the energy expenditure in (brown) adipose tissue and muscle tissue. This action is due to stimulation of the receptor TGR5 by bile acids. Recently scientists have discovered that this receptor in rodents is also expressed on the surface of intestinal L-cells (which normally secrets Glucagon-Like Peptide-1 (GLP-1) in response to nutrient stimulation). The stimulation of this receptor has shown a GLP-1 secretion from the intestinal cells which is interesting since GLP-1 has a central role in maintaining normal glucose tolerance and thus blood sugar. Given the above, bile acids has an important impact on intestinal GLP-1 secretion. Whether these scientific findings can be proven in human beings is uncertain.
The primary hypothesis is that stimulating gall bladder emptying via Cholecystokinin (CCK) in healthy subjects will result in a significant GLP-1 response. We also hypothesize that adding orally Metformin or a sequestrant ("a bile acid binder") will further enhance this GLP-1 response.

Start Date01 Jul 2012

Sponsor / Collaborator

University of Copenhagen

NCT00706381 / CompletedPhase 3IIT

Thyroid Hormones Homeostasis and Energy Metabolism Changes During Stimulation of Endogenously Secreted Bile Acids (BAs)

Postprandial thermogenesis, or thermic effect of food are terms that describe the increase in utilization of energy by the human body following a meal. The mechanisms involved in this process are believed to differ according to the type of food consumed, whether fat, protein or carbohydrate.
The bile acids (BAs), unique substances secreted by the gall bladder into the gut after a meal, play an important role in the absorption of fat and the management of cholesterol stores in the body. Recent studies suggest that BAs may also serve as regulators of energy expenditure (consumption) in the cells of our body by increasing the production of T3, an active form of thyroid hormone. T3 in turn is believed to increase the efficiency with which our bodies burn calories thereby generating heat. Although this process has been shown to be effective in rodents who demonstrated weight loss after treatment, the role of BAs in humans is poorly understood. Thus we do not know whether endogenous (produced by the body) or exogenous (taken as medication) BAs play a significant role in the maintenance of body weight. We hypothesize that, similarly to rodents, humans will respond to BAs by increasing energy expenditure via the production of the active form of thyroid hormone.
This randomized, cross-over study will look at changes in thyroid hormones and energy consumption in response to stimuli of endogenous BA secretion including dietary content, and to the intake of pharmacological doses of bile acids.
Following a two-day period of equilibration diet, 30 healthy volunteers will be randomly assigned to receive either a high-fat or high-carbohydrate isocaloric meal followed by a 6-hour metabolic chamber stay; the next day they will be crossed-over to the alternate intervention. During the following three days, the study subjects will again be randomized to receive either an intravenous injection of sincalide (the C-terminal octapeptide fragment of cholecystokinin) 0.04 mcg/kg or placebo and P.O. placebo, or I.V. placebo and 15 mg/kg of BA (ursodiol) with similar metabolic chamber stays and cross-over design.
The data gathered from this study will provide greater insight into the physiological and molecular mechanism(s) regulating the relation between endogenous bile acid secretion and energy metabolism in response to meals, as well as the role of BAs per se on energy metabolism.

Start Date23 Jun 2008

Sponsor / Collaborator

National Institute of Diabetes & Digestive & Kidney Diseases

100 Clinical Results associated with Sincalide

100 Translational Medicine associated with Sincalide

100 Patents (Medical) associated with Sincalide

1,333

Literatures (Medical) associated with Sincalide

30 Jul 2024·Journal of Neurogastroenterology and Motility

Effects of Cholecystokinin on Esophageal Motor Response to Distension in Asymptomatic Volunteers

Article

Author: Kahrilas, Peter J ; Ellison, Ashton C ; Carlson, Dustin A ; Pandolfino, John E

Background/Aims:

Cholecystokinin (CCK) administration has been shown to reduce lower esophageal sphincter (LES) pressure in normal subjects in manometric studies. Functional luminal imaging probe (FLIP) panometry offers a method to assess esophageal motility in response to sustained distension though mechanisms related to this response remain unexplored. The aim of this study is to evaluate the effect of CCK-8 on the esophageal response to distension in asymptomatic volunteers using FLIP.

Methods:

Esophageal response to distension was studied in 7 asymptomatic volunteers (mean age ± SD [27 ± 2]; 86% female) before and after CCK-8 administration in a crossover study design. During sedated endoscopy, FLIP was performed twice with CCK-8 administered via intravenous push in one of 2 protocols: during filling (n = 4) or during emptying (n = 3). Esophagogastric junction distensibility index (EGJ-DI) at 60 mL fill volume and esophageal body contractile response patterns were analyzed.

Results:

During the baseline FLIP study, all subjects had a contractile response with repetitive antegrade contractions both before and after CCK-8 administration. However, a sustained LES contraction or a sustained occluding contraction with esophageal shortening was observed in all subjects in the filling protocol, but in none during the emptying protocol. EGJ-DI was similar before and after CCK-8 during both filling (4.7 ± 1.9 mm²/mmHg vs 4.3 ± 1.8 mm²/mmHg) and emptying protocol (7.5 ± 1.4 mm²/mmHg vs 6.9 ± 0.6 mm²/mmHg).

Conclusion:

While EGJ-DI appeared unaffected by CCK-8 administration in asymptomatic volunteers, CCK induced spastic-reactive contractions of the LES during distention suggesting that exogenous CCK interferes with normal LES relaxation during secondary peristalsis.

01 May 2024·Chinese journal of integrative medicine

Paeoniflorin, the Main Monomer Component of Paeonia lactiflora, Exhibits Anti-inflammatory Properties in Osteoarthritis Synovial Inflammation

Article

Author: Zhou, Jun ; Chen, Pu ; Ma, Yu-Feng ; Ruan, An-Min ; Wang, Qing-Fu

OBJECTIVE:

To explore the mechanism of paeoniflorin (PF) on osteoarthritis (OA) synovial inflammation from network pharmacology to experimental pharmacology.

METHODS:

Targets of OA were constructed by detecting the database of network database platforms (Therapeutic Target database, DrugBank and GeneCards), and the targets of PF were constructed by PubChem and Herbal Ingredients' Targets database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these co-targeted genes were conducted via Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, and protein-protein interaction (PPI) networks were conducted via the search tool for the retrieval of interacting genes (STRING) database. Cell counting kit-8 (CCK-8) assay was performed to assess the potential toxicity of PF on human OA fibroblast-like synoviocytes (FLS), quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA) and Western blot were used to verify the potential mechanism of PF in synovial inflammation.

RESULTS:

Twenty-six co-targeted genes were identified. GO enrichment results showed that these co-targeted genes were most likely localized in the cytoplasm, and the biological processes mainly involved 'cellular response to hypoxia' 'lipopolysaccharide (LPS)-mediated signaling pathway' and 'positive regulation of gene expression'. KEGG pathway analysis indicated that these co-targeted genes may function through pathways associated with 'hypoxia-inducible factor-1 (HIF-1) signaling pathway' and 'tumor-necrosis factor (TNF) signaling pathway'. The PPI network showed that the top 3 hub genes were TP53, TNF, and CASP3. Molecular docking results showed that PF was well docking with TNF. CCK-8 showed no potential toxicity of 10, 20 and 50 µmol/L PF on human OA FLS. And PF significantly decreased the expression levels of interleukin-1 β, interleukin-6, TNF-α matrix metalloproteinase 13 (MMP13), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and TNF-α in LPS-induced OA FLS.

CONCLUSION:

PF exhibited potent anti-inflammatory effect in OA synovial inflammation.

26 Feb 2024·Biological chemistry

Mechanism of hypoxia-induced exosome circ_0051799 regulating the progression of lung adenocarcinoma

Article

Author: Zhu, Shunping ; Liao, Bihong

Abstract:

This study attempted to investigate the effect of circ_0051799 on the immune microenvironment of lung adenocarcinoma (LUAD) and the relationship between circ_0051799 and exosomes. The number and morphology of exosomes were verified by nanoparticle tracking, transmission electron microscopy and western blotting. CCK8, EdU, Transwell and flow cytometry were used to verify the regulatory role of exosomes and circ_0051799 on tumor progression. Dual luciferase reporting and RNA immunoprecipitation were used to verify the targeted regulatory relationship between circ_0051799, miR-214-3p and IGF2BP3. WB was used to verify the role of the JAK/STAT pathway in circ_0051799 regulation. Ectopic tumor grafts and in situ models were used to validate in vivo their role in regulating LUAD progression. Hypoxic environment could alter but does not alter its shape. Exosomes can participate in the regulation of macrophage polarization by circ_0051799. In vitro and in vivo assays had shown that circ_0051799 could affect the proliferation and metastasis of LUAD through targeting miR-214-3p mediated IGF2BP3 regulated JAK/STAT pathway. This study found that hypoxia can affect LUAD process by promoting the regulation of macrophage polarization by exosome circ_0051799.

News (Medical) associated with Sincalide

08 Aug 2023

·www.biospace.com

Fresenius Kabi Further Expands Radiology Portfolio with Launch of Gadobutrol Injection

FDA-approved generic for MRI procedures is fully substitutable for Gadavist® LAKE ZURICH, Ill.--(BUSINESS WIRE)-- Fresenius Kabi announced today it has launched Gadobutrol Injection, a generic substitute for the contrast agent Gadavist®, which is used in magnetic resonance imaging (MRI) procedures. Fresenius Kabi Gadobutrol Injection, a high-relaxivity macrocyclic agent, is available immediately in the United States. It is the second MRI offering in the company’s growing radiology portfolio, which also includes: Gadoterate Meglumine Injection, USP, a generic equivalent of Dotarem® Sincalide for Injection, an authorized generic of Kinevac®; and Iodixanol Injection, USP, a generic for Visipaque® "Fresenius Kabi is pleased to introduce Gadobutrol Injection as the newest addition to our U.S. radiology portfolio, expanding the range of cost-effective contrast agent options available to hospitals and clinics," said John Ducker, president and CEO of Fresenius Kabi USA. Gadobutrol Injection is a gadolinium-based contrast agent indicated for use with MRI.1 It is the fourth product offering in the Fresenius Kabi radiology portfolio, which first launched in July 2022 with the introduction of Iodixanol Injection, USP during a nationwide shortage. Gadobutrol Injection is available to order direct from the company and through wholesalers and distributors. It is currently available in 2 mL, 7.5 mL, 10 mL and 15 mL Single Dose Vials. Fresenius Kabi Gadobutrol Injection is preservative-free, and the container closure is not made with natural rubber latex. INDICATIONS AND USAGE Gadobutrol injection is a gadolinium-based contrast agent indicated for use with magnetic resonance imaging (MRI): To detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system in adult and pediatric patients, including term neonates. To assess the presence and extent of malignant breast disease in adult patients. To evaluate known or suspected supra-aortic or renal artery disease in adult and pediatric patients, including term neonates. To assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD). WARNING: NEPHROGENIC SYSTEMIC FIBROSIS (NSF) See full prescribing information for complete boxed warning Gadolinium-based contrast agents (GBCAs) increase the risk for NSF among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. The risk for NSF appears highest among patients with: Chronic, severe kidney disease (GFR < 30 mL/min/1.73m2), or Acute kidney injury. Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (for example, age > 60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing. IMPORTANT SAFETY INFORMATION Contraindications: History of severe hypersensitivity reaction to gadobutrol injection. Nephrogenic Systemic Fibrosis has occurred in patients with impaired elimination of GBCAs. Higher than recommended dosing or repeated dosing appears to increase the risk. Anaphylactic and other hypersensitivity reactions with cardiovascular, respiratory, or cutaneous manifestations, ranging from mild to severe, including death, have occurred. Monitor patients closely during and after administration of gadobutrol injection. Gadolinium is retained for months or years in brain, bone, and other organs. Adverse Events: Most common adverse reactions (incidence ≥ 0.5%) are headache, nausea, and dizziness. Pregnancy: Use only if imaging is essential during pregnancy and cannot be delayed. To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176, option 5, or FDA at 1-800-FDA-1088 or . This Important Safety Information does not include all the information needed to use Gadobutrol Injection safely and effectively. Please see full prescribing information, including BOXED WARNING, for Gadobutrol Injection at . About Fresenius Kabi Fresenius Kabi ( ) is a global health care company that specializes in medicines and technologies for infusion, transfusion, and clinical nutrition. The company’s products and services are used to help care for patients with critical and chronic conditions. The company’s U.S. headquarters is in Lake Zurich, Illinois. The company’s global headquarters is in Bad Homburg, Germany. To learn about U.S. career opportunities at Fresenius Kabi, visit us at and follow us on LinkedIn. References Gadobutrol Injection Package Insert, January 2023 *Gadavist® is a registered trademark of Bayer. *Dotarem® is a registered trademark of Guerbet. *Kinevac® is a registered trademark of Bracco Diagnostics Inc. *Visipaque® is a registered trademark of GE Healthcare.

Drug Approval

100 Deals associated with Sincalide

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KEGG	Wiki	ATC	Drug Bank
D05845	Sincalide	V04CC03	DB09142

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Gallbladder Diseases	US	Maia Pharmaceuticals, Inc.	22 Nov 2022
Intestinal Diseases	US	Maia Pharmaceuticals, Inc.	22 Nov 2022
Pancreatic Diseases	US	Maia Pharmaceuticals, Inc.	22 Nov 2022
Cholecystitis	US	Bracco Diagnostics, Inc.	21 Jul 1976

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