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1.
Int J Mol Sci ; 23(11)2022 Jun 03.
Article in English | MEDLINE | ID: mdl-35682965

ABSTRACT

Traumatic events frequently produce false fear memories. We investigated the effect of hypothalamic corticotropin-releasing factor (CRF) knockdown (Hy-Crf-KD) or overexpression (Hy-CRF-OE) on contextual fear memory, as fear stress-released CRF and hypothalamic-pituitary-adrenal axis activation affects the memory system. Mice were placed in a chamber with an electric footshock as a conditioning stimulus (CS) in Context A, then exposed to a novel chamber without CS, as Context B, at 3 h (B-3h) or 24 h (B-24h). The freezing response in B-3h was intensified in the experimental mice, compared to control mice not exposed to CS, indicating that a false fear memory was formed at 3 h. The within-group freezing level at B-24h was higher than that at B-3h, indicating that false context fear memory was enhanced at B-24h. The difference in freezing levels between B-3h and B-24h in Hy-Crf-KD mice was larger than that of controls. In Hy-CRF-OE mice, the freezing level at B-3h was higher than that of control and Hy-Crf-KD mice, while the freezing level in B-24h was similar to that in B-3h. Locomotor activity before CS and freezing level during CS were similar among the groups. Therefore, we hypothesized that Hy-Crf-KD potentiates the induction of false context fear memory, while Hy-CRF-OE enhances the onset of false fear memory formation.


Subject(s)
Adrenocorticotropic Hormone , Corticotropin-Releasing Hormone , Adrenocorticotropic Hormone/pharmacology , Animals , Corticotropin-Releasing Hormone/metabolism , Fear , Freezing Reaction, Cataleptic/physiology , Hypothalamo-Hypophyseal System/metabolism , Mice , Pituitary Hormone-Releasing Hormones/pharmacology , Pituitary-Adrenal System/metabolism
2.
Eur Surg Res ; 61(4-5): 123-129, 2020.
Article in English | MEDLINE | ID: mdl-32248190

ABSTRACT

INTRODUCTION: Pneumonia is one of the most frequently occurring complications after esophagectomy and is associated with increased operative mortality. Chronic obstructive pulmonary disease (COPD) is known to be a risk factor for pulmonary complications and operative mortality. However, in COPD patients preparing for esophagectomy, preventive measures against postoperative pneumonia have not yet been discovered. In this study, we evaluate the effect of perioperative inhaled tiotropium, a long-acting, antimuscarinic bronchodilator used in the management of COPD, on patients with COPD who undergo esophageal cancer surgery. METHODS/DESIGN: This study investigates the effect of perioperative inhaled tiotropium on patients with COPD who undergo esophagectomy. It is an open-label, randomized controlled trial conducted in a single center (EPITOPE study). A total of 32 enrolled patients are randomly assigned in a 1:1 ratio to either conventional management or inhalation of tiotropium in addition to the conventional management. Patients included in the intervention group receive tiotropium Respimat 5 µg (two inhalations of 2.5 µg) for at least 2 weeks before the esophagectomy. Following the esophagectomy, tiotropium is re-delivered, starting as early as possible and continuing until the postoperative evaluation (between 30 and 44 days after the operation). The primary outcome is the incidence of pneumonia within 30 days after esophagectomy. Secondary outcomes are the incidence of cardiovascular complications within 30 days after esophagectomy, the incidence of any postoperative complications within 30 days after esophagectomy, pulmonary function (preintervention, preoperative, and postoperative), walking distance in the incremental shuttle walking test (preintervention, preoperative, and postoperative), the incidence of adverse events, and mortality within 30 days after esophagectomy. DISCUSSION: The EPITOPE study is the first pilot study on the effects of perioperative inhaled tiotropium on patients with COPD undergoing esophagectomy. After completing this study, we will plan a multicenter RCT with the appropriate outcomes in the future.


Subject(s)
Esophageal Neoplasms/surgery , Esophagectomy/adverse effects , Pneumonia/prevention & control , Postoperative Complications/prevention & control , Pulmonary Disease, Chronic Obstructive/drug therapy , Tiotropium Bromide/administration & dosage , Administration, Inhalation , Esophagectomy/mortality , Humans , Pilot Projects , Prospective Studies
3.
J Biol Chem ; 278(38): 36748-53, 2003 Sep 19.
Article in English | MEDLINE | ID: mdl-12847109

ABSTRACT

Platelet adhesion to vascular endothelial cells is a pathophysiologically relevant cell-to-cell interaction. However, the mechanisms underlying this cellular interaction are incompletely understood. In search of the ligand for CD226 adhesion molecule expressed on platelets, we found that human umbilical vein endothelial cells (HUVEC) express significant amount of putative CD226 ligand. We demonstrated that thrombin-activated, but not resting, platelets bind to intact HUVEC. Anti-CD226 monoclonal antibody specifically inhibited the binding, indicating that CD226 mediates the intercellular binding between thrombin-activated platelets and HUVEC. We also demonstrated that platelet activation with thrombin induces tyrosine phosphorylation of CD226 as well as CD226-mediated platelet adhesion. Moreover, experiments using mutant transfectants suggested that the tyrosine at residue 322 of CD226 plays an important role for its adhesive function. CD226 was also expressed on primary megakaryocytes and megakaryocytic cell lines. Anti-CD226 monoclonal antibody inhibited binding of megakaryocytic cell lines to HUVEC. Taken together, these results reveal a novel mechanism for adhesion of platelets and megakaryocytic cells to vascular endothelial cells.


Subject(s)
Antigens, Differentiation, T-Lymphocyte/biosynthesis , Antigens, Differentiation, T-Lymphocyte/chemistry , Blood Platelets/metabolism , Endothelium, Vascular/cytology , Megakaryocytes/metabolism , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/metabolism , COS Cells , Cell Adhesion , Cell Line , Cells, Cultured , Flow Cytometry , Fluoresceins/metabolism , Humans , Ligands , Microscopy, Fluorescence , Mutation , Phosphorylation , Thrombin/chemistry , Transfection , Tyrosine/chemistry , Tyrosine/metabolism , Umbilical Veins/cytology
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