Endothelin-1 increases Na-K-2Cl cotransporter-1 expression in cultured astrocytes and in traumatic brain injury model: An involvement of HIF1α activation.

Na-K-2Cl cotransporter-1 (NKCC1) is present in brain cells, including astrocytes. The expression of astrocytic NKCC1 increases in the acute phase of traumatic brain injury (TBI), which induces brain edema. Endothelin-1 (ET-1) is a factor that induces brain edema and regulates the expression of several pathology-related genes in astrocytes.

Roles of astrocytic sonic hedgehog production and its signal for regulation of the blood-brain barrier permeability.

Sonic hedgehog (Shh) is a secreted glycopeptide belonging to the hedgehog family that is essential for morphogenesis during embryonic development. The Shh signal is mediated by two membrane proteins, Patched-1 (Ptch-1) and Smoothened (Smo), following the activation of transcription factors such as Gli. Shh decreases the permeability of the blood-brain barrier (BBB) and plays a key role in its function.

Histamine H Receptor-Mediated JNK Phosphorylation Is Regulated by G Protein-Dependent but Arrestin-Independent Pathways.

Arrestins are known to be involved not only in the desensitization and internalization of G protein-coupled receptors but also in the G protein-independent activation of mitogen-activated protein (MAP) kinases, such as extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), to regulate cell proliferation and inflammation. Our previous study revealed that the histamine H receptor-mediated activation of ERK is dually regulated by G proteins and arrestins. In this study, we investigated the roles of G proteins and arrestins in the H receptor-mediated activation of JNK in Chinese hamster ovary (CHO) cells expressing wild-type (WT) human H receptors, the G protein-biased mutant S487TR, and the arrestin-biased mutant S487A.

Mortal Dangers of Adult-Onset IgA Vasculitis.

IgA vasculitis (IgAV), previously known as Henoch Schoenlein purpura (HSP), is a leukocytoclastic vasculitis subtype predominantly amongst the pediatric patient population involving IgA dominant immune complex deposits attacking small vessel walls. While it oftentimes follows upper respiratory infections and presents with palpable purpuras, IgAV can also present in the adult patient population and lead to systemic inflammation. In this case report, we present the case of an adult-onset IgAV complicated via gastrointestinal perforation, acute kidney injury secondary to IgA nephritis, and circulatory shock.

Roles of Astrocytic Endothelin ET Receptor in Traumatic Brain Injury.

Traumatic brain injury (TBI) is an intracranial injury caused by accidents, falls, or sports. The production of endothelins (ETs) is increased in the injured brain. ET receptors are classified into distinct types, including ET receptor (ET-R) and ET receptor (ET-R).

Selective histamine H receptor agonists alleviate blood-brain barrier disruption by promoting the expression of vascular protective factors following traumatic brain injury in mice.

Histamine is a major neurotransmitter and alleviates neuronal damage after ischemic injury via H receptors. Herein, we investigated the effects of H receptor agonists on the blood-brain barrier (BBB) disruption after traumatic brain injury (TBI). Male ddY mice were used to generate the TBI model, in which a fluid percussion injury (FPI) was induced by a hydraulic impact.

Molecular Determinants of the Kinetic Binding Properties of Antihistamines at the Histamine H Receptors.

The binding affinity of ligands for their receptors is determined by their kinetic and thermodynamic binding properties. Kinetic analyses of the rate constants of association and dissociation ( and , respectively) of antihistamines have suggested that second-generation antihistamines have a long duration of action owing to the long residence time (1/) at the H receptors. In this study, we examined the relationship between the kinetic and thermodynamic binding properties of antihistamines, followed by an evaluation of the structural determinants responsible for their kinetic binding properties using quantitative structure-activity relationship (QSAR) analyses.

Differential Regulation of Bilastine Affinity for Human Histamine H Receptors by Lys 179 and Lys 191 via Its Binding Enthalpy and Entropy.

Bilastine, a zwitterionic second-generation antihistamine containing a carboxyl group, has higher selectivity for H receptors than first-generation antihistamines. Ligand-receptor docking simulations have suggested that the electrostatic interaction between the carboxyl group of second-generation antihistamines and the amino group of Lys179 and Lys191 of human H receptors might contribute to increased affinity of these antihistamines to H receptors. In this study, we evaluated the roles of Lys179 and Lys191 in regulating the electrostatic and hydrophobic binding of bilastine to H receptors by thermodynamic analyses.

Roles of Lys191 and Lys179 in regulating thermodynamic binding forces of ligands to determine their binding affinity for human histamine H receptors.

Docking simulations based on the crystal structure of human histamine H receptors have predicted crucial roles of Lys191 and Lys179, which exist at the entrance of the ligand-binding pocket, in increasing the H-receptor selectivity for carboxylated second-generation antihistamines via electrostatic interaction. In this study, we evaluated the roles of Lys191 and Lys179 in regulating the thermodynamic binding forces of non-carboxylated and carboxylated antihistamines that determine their binding affinity for human H receptors. The binding enthalpy and entropy of the 3 sets of non-carboxylated and corresponding carboxylated antihistamines (doxepin and olopatadine, desloratadine and loratadine, and terfenadine and fexofenadine, respectively) were estimated using the van't Hoff equation with the dissociation constants obtained from the displacement curves of the non-carboxylated and carboxylated antihistamines against the binding of [H]mepyramine to the membrane preparations of Chinese hamster ovary cells expressing human H receptors at various temperatures, ranging from 4 °C to 37 °C.

Epidermoid cyst within an intrapancreatic accessory spleen exhibiting abrupt changes in serum carbohydrate antigen 19-9 level: a case report.

Background: Epidermoid cyst within an intrapancreatic accessory spleen (ECIAS) is a rare disease. While the detection of solid components relevant to an accessory spleen is a key diagnostic finding, the differential diagnosis between ECIAS and malignant tumors is difficult without resection in patients with no other findings of an accessory spleen.

Case Presentation: A 73-year-old male was found to have an elevated carbohydrate antigen (CA) 19-9 level (95 U/mL) at an annual checkup, and a cystic lesion in the pancreatic tail was located by abdominal ultrasound.

Validation and clinical usefulness of pre- and postoperative systemic inflammatory parameters as prognostic markers in patients with potentially resectable pancreatic cancer.

Background: Several preoperative systemic inflammatory parameters, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and Glasgow prognostic score, have been reported to be associated with the prognosis of solid tumors. In this study, we compared pre- and postoperative hematological inflammatory parameters and validated their prognostic significance in pancreatic cancer patients who underwent surgical resection.

Methods: Clinical records from 211 consecutive pancreatic cancer patients who underwent surgical resection at our institution were retrospectively analyzed.

Human equilibrative nucleoside transporter-1 expression is a predictor in patients with resected pancreatic cancer treated with adjuvant S-1 chemotherapy.

The high expression of human equilibrative nucleoside transporter-1 (hENT1) and the low expression of dihydropyrimidine dehydrogenase (DPD) are reported to predict a favorable prognosis in patients treated with gemcitabine (GEM) and 5-fluorouracil (5FU) as the adjuvant setting, respectively. The expression of hENT1 and DPD were analyzed in patients registered in the JASPAC 01 trial, which showed a better survival of S-1 over GEM as adjuvant chemotherapy after resection for pancreatic cancer, and their possible roles for predicting treatment outcomes and selecting a chemotherapeutic agent were investigated. Intensity of hENT1 and DPD expression was categorized into no, weak, moderate or strong by immunohistochemistry staining, and the patients were classified into high (strong/moderate) and low (no/weak) groups.

Outcomes in patients with pancreatic cancer as a secondary malignancy: a retrospective single-institution study.

Purpose: This study aimed to evaluate the clinicopathological features and oncological outcomes of pancreatic cancer (PC) patients with prior malignancies (2nd primary PC) compared with those of patients without any prior malignancies in their history (1st primary PC).

Methods: We retrospectively reviewed clinical data from 185 PC patients undergoing surgical resection. Patients were divided into the 1st and 2nd primary PC groups.

Nadir lymphocytopenia as a risk factor of bloodstream infection during molecular targeting pharmacotherapy in multiple myeloma.

Objective: Molecular targeting pharmacotherapy (MTP) with proteasome inhibitors and immunomodulatory drugs has led to a remarkable improvement in the effectiveness of multiple myeloma (MM) therapy. However, the effect of MTP on the occurrence of infections in patients with MM remains unclear. We aimed to identify the incidence of and risk factors for bloodstream infection (BSI) in patients with MM undergoing MTP.

Predictive Factors for Elevated Postoperative Carbohydrate Antigen 19-9 Levels in Patients With Resected Pancreatic Cancer.

Aim: In this study, we investigated the clinical significance of postoperative serum carbohydrate antigen (CA) 19-9 in patients with pancreatic ductal carcinoma (PDAC).

Patients And Methods: A series of 116 patients with macroscopically curative PDAC resection was retrospectively evaluated. The cut-off level for elevated postoperative CA 19-9 was 37 U/ml.

Association of Preoperative Platelet-to-Lymphocyte Ratio with Poor Outcome in Patients with Distal Cholangiocarcinoma.

Background: Several preoperative systemic inflammatory parameters, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and Glasgow Prognostic Score, have been reported to be associated with the prognosis of solid tumors. However, there are conflicting survival data regarding these parameters in cholangiocarcinoma.

Objectives: In this study, we performed a retrospective cohort analysis of patients with distal cholangiocarcinoma (DCC) who underwent surgical resection to evaluate the prognostic value of a cluster of preoperative hematological inflammatory parameters for survival.

Differential Regulation of Thermodynamic Binding Forces of Levocetirizine and ()-Cetirizine by Lys191 in Human Histamine H₁ Receptors.

Cetirizine is a zwitterionic second-generation antihistamine containing - and -enantiomers, levocetirizine, and ()-cetirizine. Levocetirizine is known to have a higher affinity for the histamine H₁ receptors than ()-cetirizine; ligand-receptor docking simulations have suggested the importance of the formation of a salt bridge (electrostatic interaction) between the carboxylic group of levocetirizine and the Lys191 residue at the fifth transmembrane domain of human histamine H₁ receptors. In this study, we evaluated the roles of Lys191 in the regulation of the thermodynamic binding forces of levocetirizine in comparison with ()-cetirizine.

Rapid progression of a granulocyte colony-stimulating factor-producing liver tumor metastasized from esophagogastric junction cancer: A case report and literature review.

The current study presents the case of a 72-year-old woman with a rapidly enlarged liver metastasis from esophagogastric junction (EGJ) cancer, accompanied by progressive leukocytosis (47,680/µl) and elevated serum granulocyte colony-stimulating factor (G-CSF; 779 pg/ml). The patient underwent right hemihepatectomy 26 months after a total gastrectomy. On the seventh post-operative day the patient's leukocyte count and serum G-CSF level decreased to 4,280/µl and ≤19.

Health-related quality of life of adjuvant chemotherapy with S-1 versus gemcitabine for resected pancreatic cancer: Results from a randomised phase III trial (JASPAC 01).

Background: Adjuvant chemotherapy with S-1 for resected pancreatic cancer demonstrated survival benefits compared with gemcitabine in the JASPAC 01 trial. We investigated the effect of these agents on health-related quality of life (HRQOL) of patients in the JASPAC 01 trial.

Methods: Patients with resected pancreatic cancer were randomly assigned to receive gemcitabine (1000 mg/m weekly for three of four weeks for up to six cycles) or S-1 (40, 50, or 60 mg twice daily for four of six weeks for up to four cycles).

Ca -dependent down-regulation of human histamine H receptors in Chinese hamster ovary cells.

G protein-coupled human histamine H receptors in Chinese hamster ovary cells stimulated with histamine undergo clathrin-dependent endocytosis followed by proteasome/lysosome-mediated down-regulation. In this study, we evaluated the effects of a sustained increase in intracellular Ca concentrations induced by a receptor-bypassed stimulation with ionomycin, a Ca ionophore, on the endocytosis and down-regulation of H receptors in Chinese hamster ovary cells. All cellular and cell-surface H receptors were detected by the binding of [ H]mepyramine to intact cells sensitive to the hydrophobic and hydrophilic H receptor ligands, mepyramine and pirdonium, respectively.

Clinical implications of the proliferative ability of the squamous component regarding tumor progression of adenosquamous carcinoma of the pancreas: A preliminary report.

Objectives: The objectives of this study were to examine the clinicopathological characteristics of patients with adenosquamous carcinoma of the pancreas (ASCP) and assess whether the proliferative ability of the squamous cell carcinoma (SCC) component contributes to either its proportion within the tumor or tumor progression.

Methods: We retrospectively reviewed 12 patients with resected ASCP and compared their clinicopathological characteristics with those of 161 patients with adenocarcinoma of the pancreas (ACP). The Ki-67 indexes of the separate ASCP components were assessed.

Inhibition of Ectopic Arginine Vasopressin Production by Phenytoin in the Small Cell Lung Cancer Cell Line Lu-165.

Phenytoin, a voltage-gated sodium channel (Na channel) antagonist, reportedly inhibits arginine vasopressin (AVP) release from an isolated rat neurohypophysis. So far, it is uncertain whether phenytoin has a direct action on ectopic AVP-producing neuroendocrine tumors. We studied the effect of phenytoin on the release of copeptin, the C-terminal fragment of pro-AVP, and expression of AVP gene in the human small cell lung cancer cell line Lu-165.

Reassessment of the clinical significance of portal-superior mesenteric vein invasion in borderline resectable pancreatic cancer.

Objective: The principal objective of this study is to clarify the prognostic significance of borderline resectable pancreatic cancer (BRPC). The second objective is to evaluate the prognostic impact of the depth of pathological venous invasion.

Methods: The study included 122 pancreatic cancer patients who underwent curative surgery.