Search results for "Indole"
showing 10 items of 570 documents
Molecular mechanisms mediating the neuroprotective role of the selective estrogen receptor modulator, bazedoxifene, in acute ischemic stroke: A compa…
2017
As the knowledge on the estrogenic system in the brain grows, the possibilities to modulate it in order to afford further neuroprotection in brain damaging disorders so do it. We have previously demonstrated the ability of the selective estrogen receptor modulator, bazedoxifene (BZA), to reduce experimental ischemic brain damage. The present study has been designed to gain insight into the molecular mechanisms involved in such a neuroprotective action by investigating: 1) stroke-induced apoptotic cell death; 2) expression of estrogen receptors (ER) ERα, ERβ and the G-protein coupled estrogen receptor (GPER); and 3) modulation of MAPK/ ERK1/2 and PI3K/Akt signaling pathways. For comparison, …
Nintedanib plus docetaxel after progression on immune checkpoint inhibitor therapy: insights from VARGADO, a prospective study in patients with lung …
2019
Aim: To assess outcomes in patients with advanced adenocarcinoma non-small-cell lung cancer who received nintedanib plus docetaxel after progression on prior chemotherapy followed by immune checkpoint inhibitor (ICI) therapy. Patients & methods: VARGADO is a prospective, noninterventional study. We describe initial data from a cohort of 22 patients who received nintedanib plus docetaxel after chemotherapy and ICI therapy. Results: Median progression-free survival with nintedanib plus docetaxel was 5.5 months (95% CI: 1.9–8.7 months). The objective response rate was 7/12 (58%) and the disease control rate was 10/12 (83%). Data for overall survival rate 12 months after the start of treat…
Plasminogen activator inhibitor‐1 augments damage by impairing fibrinolysis after traumatic brain injury
2019
Objective Plasminogen activator inhibitor-1 (PAI-1) is the key endogenous inhibitor of fibrinolysis, and enhances clot formation after injury. In traumatic brain injury, dysregulation of fibrinolysis may lead to sustained microthrombosis and accelerated lesion expansion. In the present study, we hypothesized that PAI-1 mediates post-traumatic malfunction of coagulation, with inhibition or genetic depletion of PAI-1 attenuating clot formation and lesion expansion after brain trauma. Methods We evaluated PAI-1 as a possible new target in a mouse controlled cortical impact (CCI) model of traumatic brain injury. We performed the pharmacological inhibition of PAI-1 with PAI-039 and stimulation b…
Mast cells' involvement in inflammation pathways linked to depression: evidence in mastocytosis
2016
International audience; Converging sources of evidence point to a role for inflammation in the development of depression, fatigue and cognitive dysfunction. More precisely, the tryptophan (TRP) catabolism is thought to play a major role in inflammation-induced depression. Mastocytosis is a rare disease in which chronic symptoms, including depression, are related to mast cell accumulation and activation. Our objectives were to study the correlations between neuropsychiatric features and the TRP catabolism pathway in mastocytosis in order to demonstrate mast cells' potential involvement in inflammation-induced depression. Fifty-four patients with mastocytosis and a mean age of 50.1 years were…
Effect of some indole derivatives on xenobiotic metabolism and xenobiotic-induced toxicity in cultured rat liver slices.
1999
In this study the effect of some indole derivatives on xenobiotic metabolizing enzymes and xenobiotic-induced toxicity has been examined in cultured precision-cut liver slices from male Sprague-Dawley rats. While treatment of rat liver slices for 72 hours with 2-200 microM of either indole-3-carbinol (I3C) or indole-3-acetonitrile (3-ICN) had little effect on cytochrome P-450 (CYP)-dependent enzyme activities, enzyme induction was observed after in vivo administration of I3C. The treatment of rat liver slices with 50 microM 3,3'-diindolylmethane (DIM; a dimer derived from I3C under acidic conditions) for 72 hours resulted in a marked induction of CYP-dependent enzyme activities. DIM appears…
Histamine inhibits 5-hydroxytryptamine release from the porcine small intestine: Involvement of H3 receptors
1992
Abstract Strips of the porcine small intestine were incubated in vitro, and the release of 5-hydroxytryptamine (5-HT) was determined by high-pressure liquid chromatography with electrochemical detection. Removal of the mucosa resulted in a large reduction (95%) of tissue 5-HT, suggesting that enterochromaffin cells are the main source of 5-HT. The release of 5-HT was reduced by 70% after omission of calcium. Tetrodotoxin and hexamethonium reduced the release of 5-HT by 30%–40% in a nonadditive manner, indicating a spontaneous neuronal (nicotinic) excitatory input to the enterochromaffin cells. Histamine inhibited the release of 5-HT by about 50%. This effect was not affected by mepyramine o…
BCL-XL inhibition induces an FGFR4-mediated rescue response in colorectal cancer
2022
The heterogeneous therapy response observed in colorectal cancer is in part due to cancer stem cells (CSCs) that resist chemotherapeutic insults. The anti-apoptotic protein BCL-XL plays a critical role in protecting CSCs from cell death, where its inhibition with high doses of BH3 mimetics can induce apoptosis. Here, we screen a compound library for synergy with low-dose BCL-XL inhibitor A-1155463 to identify pathways that regulate sensitivity to BCL-XL inhibition and reveal that fibroblast growth factor receptor (FGFR)4 inhibition effectively sensitizes to A-1155463 both in vitro and in vivo. Mechanistically, we identify a rescue response that is activated upon BCL-XL inhibition and leads …
GABA receptors are involved in the modulation of the release of 5-hydroxytryptamine from the vascularly perfused small intestine of the guinea-pig
1989
Isolated small intestinal segments of the guinea-pig were perfused arterially and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) into the portal venous effluent was determined by HPLC with electrochemical detection. Test substances were applied intraarterially. Muscimol (1 microM) time dependently first increased then decreased the release of 5-HT and 5-HIAA. The stimulatory effect was prevented by tetrodotoxin (TTx) or scopolamine, indicating that it was mediated by the release of acetylcholine. Bicuculline concentration dependently decreased (1 microM) or increased (10, 50 microM) the release of 5-HT and 5-HIAA, indicating that endogenous GABA also activ…
Involvement of CB1 and CB2 receptors in the modulation of cholinergic neurotransmission in mouse gastric preparations.
2007
Abstract While most of the studies concerning the role of cannabinoids on gastric motility have focused the attention on the gastric emptying in in vivo animal models, there is little information about the cannabinoid peripheral influence in the stomach. In addition, the functional features of CB2 receptors in the gastrointestinal tract have been poorly characterized. The purpose of the present study was to investigate the effects of cannabinoid drugs on the excitatory cholinergic and inhibitory non-adrenergic non-cholinergic (NANC) neurotransmission in mouse isolated gastric preparations. Intraluminal pressure from isolated whole stomach was recorded and mechanical responses induced by ele…
Association of a functional deficit of the BKCa channel, a synaptic regulator of neuronal excitability, with autism and mental retardation
2006
International audience; Objective: Autism is a complex, largely genetic psychiatric disorder. In the majority of cases, the cause of autism is not known, but there is strong evidence for a genetic etiology. To identify candidate genes, the physical mapping of balanced chromosomal aberrations is a powerful strategy, since several genes have been characterized in numerous disorders. In this study, the authors analyzed a balanced reciprocal translocation arising de novo in a subject with autism and mental retardation. Method: The authors performed the physical mapping of the balanced 9q23/ 10q22 translocation by fluorescent in situ hybridization experiments using bacterial artificial chromosom…