Fluvoxamine Attenuated Endoplasmic Reticulum Stress-Induced Leptin Resistance

Increasing evidence indicates that endoplasmic reticulum stress (ER stress) is involved in the development of metabolic syndrome. However, pharmacological treatments targeting ER stress are not well understood. In the present study, we found that fluvoxamine, a selective serotonin reuptake inhibitor used for depression, can attenuate ER stress-induced “leptin resistance,” i.e., insensitivity to the anti-obesity hormone leptin. Treatment with tunicamycin, an ER stress-inducing reagent, caused cell death which was significantly inhibited by fluvoxamine. Leptin activates JAK2–STAT3 signaling. ER stress caused an impairment of leptin-induced STAT3 phosphorylation which was reversed by fluvoxamine. Fluvoxamine would be a novel leptin-sensitizing drug, which targets ER stress

Myeloid Differentiation Factor 88 (MyD88)-Deficiency Increases Risk of Diabetes in Mice

BACKGROUND: Multiple lines of evidence suggest innate immune response pathways to be involved in the development of obesity-associated diabetes although the molecular mechanism underling the disease is unknown. Recent observations suggest that saturated fatty acids can act as a ligand for toll-like receptor (TLR) 4, which is thought to mediate obesity-associated insulin resistance. Myeloid differentiation factor 88 (MyD88) is an adapter protein for TLR/IL-1 receptor signaling, which is involved in the activation of inflammatory pathways. To evaluate molecular mechanisms linking obesity-associated diabetes down-stream of TLR4, we investigated physiological role of MyD88 in high-fat diet (HFD)-induced obesity. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we found MyD88-deficient mice fed a HFD had increased circulating levels of insulin, leptin and cholesterol, as well as liver dysfunction (increased induction of ALT levels, increased activation of JNK and cleavage of PARP), which were linked to the onset of severe diabetes. On the other hand, TNF-alpha would not be involved in HFD-induced diabetes in MyD88-deficient mice, because TNF-alpha level was attenuated in MyD88-deficient mice fed with HFD. CONCLUSIONS/SIGNIFICANCE: The present finding of an unexpected role for MyD88 in preventing diabetes may provide a potential novel target/strategy for treating metabolic syndrome

Impending Gastric Rupture in a Neonate with Gastric Outlet Obstruction due to Malrotation

This is a case report of a neonate with impending gastric rupture due to malrotation with gastric outlet obstruction. A preoperative plain abdominal X-ray showed expansion of the gastric bubble. A barium meal demonstrated an unusual bulging of the gastric wall extending from the fundus to the body of the stomach on the greater curvature side and malrotation of the duodenal loop. At operation a malrotation with volvulus and a rupture of the seromuscular layer with bulging of the mucosa in the stomach was found. We think that this unusual bulging of the gastric wall in the barium meal is an important radiological sign of impending gastric rupture

Increased isoprostane levels in oleic acid-induced lung injury

The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2 alpha). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.ArticleBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 388(2):297-300 (2009)journal articl

Prevalence of gastroesophageal reflux disorder in arrhythmic patients and adjunctive effects of proton pump inhibitors on comorbid atrial fibrillation

Background: Although the coexistence of atrial fibrillation (AF) and gastroesophageal reflux disorder (GERD) has been reported, the prevalence of GERD in arrhythmic patients remains unknown. This study aimed to investigate the relationship between GERD and several kinds of arrhythmia, and the therapeutic effects of proton pump inhibitors (PPI) on AF.Methods: In Study 1, patients with various kinds of arrhythmia (n=147) including AF (n=98) were administered a GERD-specific questionnaire (F-scale). In Study 2, patients with AF and GERD (n=27) responded to an AF-specific questionnaire (AFQLQ) before and after the additive PPI therapy to explore the effects of PPI on comorbid AF. In Study 3, device memory was assessed as it is related to PPI administration in pacemaker patients with GERD and AF (n=5) to study the effects of PPI on device-documented AF.Results: Left atrial (LA) size and F-scale scores in AF patients were the largest among the arrhythmic patients in Study 1. Logistic regression analysis showed no independent determinants of GERD. F-scale scores and AFQLQ scores showed temporal and partial correlations and significant improvement after starting PPI in Study 2. However, device interrogation confirmed limited AF improvement by starting PPI in Study 3.Conclusions: GERD is prevalent in AF patients. LA size is not an independent determinant of GERD. Symptoms of AF were improved, whereas device-documented paroxysms of AF were not ameliorated by PPI administration. A large-scale prospective study is required to conclude the efficacy of PPI on the comorbid AF

Molecular phylogeny and evolution of alcohol dehydrogenase (Adh) genes in legumes

BACKGROUND: Nuclear genes determine the vast range of phenotypes that are responsible for the adaptive abilities of organisms in nature. Nevertheless, the evolutionary processes that generate the structures and functions of nuclear genes are only now be coming understood. The aim of our study is to isolate the alcohol dehydrogenase (Adh) genes in two distantly related legumes, and use these sequences to examine the molecular evolutionary history of this nuclear gene. RESULTS: We isolated the expressed Adh genes from two species of legumes, Sophora flavescens Ait. and Wisteria floribunda DC., by a RT-PCR based approach and found a new Adh locus in addition to homologues of the Adh genes found previously in legumes. To examine the evolution of these genes, we compared the species and gene trees and found gene duplication of the Adh loci in the legumes occurred as an ancient event. CONCLUSION: This is the first report revealing that some legume species have at least two Adh gene loci belonging to separate clades. Phylogenetic analyses suggest that these genes resulted from relatively ancient duplication events

Super responder of critical COVID-19 case

This report presents a case of a 74-year-old man who showed dramatic therapeutic response to treatment of coronavirus infectious disease-19 (COVID-19) pneumonia. He reported four-day history of sustained fever and acute progressive dyspnea. He developed severe respiratory failure, underwent urgent endotracheal intubation and showed marked elevation of inflammatory and coagulation markers such as c-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH) and D-dimer. Chest computed tomography (CT) demonstrated diffuse consolidation and ground glass opacity (GGO). We diagnosed critical COVID-19 pneumonia with detailed sick contact history and naso-pharyngeal swab of a reverse-transcriptase-polymerase-chain reaction (RT-PCR) assay testing. He received anti-viral drug, anti-interleukin (IL-6) receptor antagonist and intravenous methylprednisolone. After commencing combined intensive therapy, he showed dramatic improvement of clinical condition, serum biomarkers and radiological findings. Early diagnosis and rapid critical care management may provide meaningful clinical benefit even if severe case