Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H 2O 2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is closely related to gut-microbiome. There is a paucity of research on which strains of gut microbiota affect the progression of NAFLD. This study explored the NAFLD-associated microbiome in humans and the role of Lactobacillus in the progression of NAFLD in mice. Methods: The gut microbiome was analyzed via next-generation sequencing in healthy people (n=37) and NAFLD patients with elevated liver enzymes (n=57). Six-week-old male C57BL/6J mice were separated into six groups (n=10 per group; normal, Western, and four Western diet + strains [109 colony-forming units/g for 8 weeks; L. acidophilus, L. fermentum, L. paracasei, and L. plantarum]). Liver/body weight ratio, liver pathology, serum analysis, and metagenomics in the mice were examined. Results: Compared to healthy subjects (1.6±4.3), NAFLD patients showed an elevated Firmicutes/Bacteroidetes ratio (25.0±29.0) and a reduced composition of Akkermansia and L. murinus (P<0.05). In the animal experiment, L. acidophilus group was associated with a significant reduction in liver/body weight ratio (5.5±0.4) compared to the Western group (6.2±0.6) (P<0.05). L. acidophilus (41.0±8.6), L. fermentum (44.3±12.6), and L. plantarum (39.0±7.6) groups showed decreased cholesterol levels compared to the Western group (85.7±8.6) (P<0.05). In comparison of steatosis, L. acidophilus (1.9±0.6), L. plantarum (2.4±0.7), and L. paracasei (2.0±0.9) groups showed significant improvement of steatosis compared to the Western group (2.6±0.5) (P<0.05). Conclusions Ingestion of Lactobacillus, such as L. acidophilus, L. fermentum, and L. plantarum, ameliorates the progression of nonalcoholic steatosis by lowering cholesterol. The use of Lactobacillus can be considered as a useful strategy for the treatment of NAFLD.

Aldose reductase (AR) protein, a member of the NADPH-dependent aldo-keto reductase family, reduces a wide range of aldehydes and enhances cell survival by inhibition of oxidative stress. Oxidative stress is known as one of the major pathological factor in ischemia. Since the precise function of AR protein in ischemic injury is fully unclear, we examined the function of AR protein in hippocampal neuronal (HT-22) cells and in an animal model of ischemia in this study. Cell permeable Tat-AR protein was produced by fusion of protein transduction domain in Tat for delivery into the cells. Tat-AR protein transduced into HT-22 cells and significantly inhibited cell death and regulated the mitogen-activate protein kinases (MAPKs), Bcl-2, Bax, and Caspase-3 under oxidative stress condition. In an ischemic animal model, Tat-AR protein transduced into the brain tissues through the blood-brain barrier (BBB) and drastically decreased neuronal cell death in hippocampal CA1 region. These results indicate that transduced Tat-AR protein has protective effects against oxidative stress-induced neuronal cell death in vitro and in vivo, suggesting that Tat-AR protein could be used as potential therapeutic agent in ischemic injury.
Aldehyde Reductase ; Aldehydes ; Blood-Brain Barrier ; Brain ; CA1 Region, Hippocampal ; Caspase 3 ; Cell Death ; Cell Survival ; Humans ; In Vitro Techniques ; Ischemia ; Models, Animal ; Neurons ; Oxidative Stress ; Oxidoreductases ; Protein Kinases

Mirizzi syndrome is a rare complication, resulting in bile duct obstruction and jaundice that usually arise from impacted gallstone in the cystic duct or neck of the gallbladder. It is vitally important to confirm underlying cystic duct anomaly in Mirizzi syndrome since it can produce surgical difficulty and higher complications. Generally, Mirizzi syndrome is treated surgically while endoscopic treatment is limited. Herein, we present Mirizzi syndrome with low lying cystic duct and remnant cyst duct calculi treated successfully by biliary stent and administration of choleretic agent, following by balloon dilatation on cystic duct and balloon extraction of the stone.
Calculi ; Cholangiopancreatography, Endoscopic Retrograde ; Cholangitis ; Cholestasis ; Cystic Duct* ; Deception* ; Dilatation ; Gallbladder ; Gallstones ; Humans ; Jaundice ; Mirizzi Syndrome* ; Neck ; Stents

Mirizzi syndrome is a rare complication, resulting in bile duct obstruction and jaundice that usually arise from impacted gallstone in the cystic duct or neck of the gallbladder. It is vitally important to confirm underlying cystic duct anomaly in Mirizzi syndrome since it can produce surgical difficulty and higher complications. Generally, Mirizzi syndrome is treated surgically while endoscopic treatment is limited. Herein, we present Mirizzi syndrome with low lying cystic duct and remnant cyst duct calculi treated successfully by biliary stent and administration of choleretic agent, following by balloon dilatation on cystic duct and balloon extraction of the stone.
Calculi ; Cholangiopancreatography, Endoscopic Retrograde ; Cholangitis ; Cholestasis ; Cystic Duct* ; Deception* ; Dilatation ; Gallbladder ; Gallstones ; Humans ; Jaundice ; Mirizzi Syndrome* ; Neck ; Stents

The title of page 189 should be corrected.

BACKGROUND: The aim of this study is to describe the clinical course and outcome of patients who were diagnosed with acute respiratory distress syndrome (ARDS) caused by scrub typhus and who received ventilator care in the intensive care units (ICU) of two university hospitals. METHODS: We performed a retrospective analysis of all adult ventilated patients who were diagnosed with ARDS caused by scrub typhus. RESULTS: Eleven (1.7%) of 632 scrub typhus patients were diagnosed with ARDS (median age 72; seven were male). Eight patients had underlying diseases, the most common of which was hypertension (four patients). Eight patients (72.7%) were admitted in November. The most common chief complaints of the patients were fever and rash (63.6%). All patients had skin eschar and rash; seven were treated for shock. On the day of diagnosis with ARDS, the median Acute Physiology and Chronic Health Evaluation score was 20 (range 11-28) and Sequential Organ Failure Assessment score was 7 (range 4-14). All patients had PaO2/FiO2 < 200 mmHg, high serum aspartate aminotransferase level (> 40 IU/L), and hypoalbuminemia (< 3.3 g/dl). Nine patients were treated with doxycycline on the day of admission. Their median lengths of stay in the ICU and hospital were 10 (range 4-65) and 14 (4-136) days, respectively. The mortality rate during treatment in the hospital was 36.4%. CONCLUSIONS: In our study, the risk of ARDS among patients diagnosed with scrub typhus was at least 1.7%, with a hospital mortality rate of 36.4%.
Adult ; APACHE ; Aspartate Aminotransferases ; Diagnosis ; Doxycycline ; Exanthema ; Fever ; Hospital Mortality ; Hospitals, University ; Humans ; Hypertension ; Hypoalbuminemia ; Intensive Care Units ; Mortality ; Respiratory Distress Syndrome, Adult* ; Retrospective Studies ; Scrub Typhus* ; Shock ; Skin ; Ventilators, Mechanical

The title of page 189 should be corrected.

OBJECTIVES: Previous studies suggest that the cannabinoid receptor 1 (CNR1) gene could be an important candidate gene for schizophrenia. According to linkage studies, this gene is located on chromosome 6q14-q15, which is known to harbor the schizophrenia susceptibility locus (locus 5, SCZ5, OMIM 803175). The pharmacological agent delta-9-tetrahydrocannabinol (Delta-9-THC) seems to elicit the symptoms of schizophrenia. The association between CNR1 polymorphisms and schizophrenia is actively being investigated, and some studies have linked the AAT-trinucleotide repeats in CNR1 to the onset of schizophrenia. In this study, we have investigated the association between the AAT-trinucleotide repeats in CNR1 and schizophrenia by studying schizophrenia patients and healthy individuals from Korea. METHODS: DNA was extracted from the blood samples of 394 control subjects and 337 patients diagnosed with schizophrenia (as per the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria). After polymerase chain reaction amplification, a logistic regression analysis, with age and gender as the covariates, was performed to study the variations in the AAT-repeat polymorphisms between the two groups. RESULTS: In total, 8 types of trinucleotide repeats were identified, each containing 7, 8, 10, 11, 12, 13, 14, and 15 repeats, respectively. (AAT)13 allele was most frequently observed, with a frequency of 33.6% and 31.6% in the patient and control groups, respectively. The frequency of the other repeat alleles in the patient group (in the decreasing order) was as follows : (AAT)13 33.6%, (AAT)14 21.6%, (AAT)12 18.5%, and (AAT)7 11.1%. The frequency of the repeat alleles in the control group (in the decreasing order) was as follows : (AAT)13 31.6%, (AAT)14 24.5%, (AAT)12 17.2%, and (AAT)7 11.6%. However, there were no significant differences in the AAT-repeat polymorphisms of the CNR1 gene between the patient group and the control group. CONCLUSIONS: Although our study revealed no significant association of the AAT-repeat polymorphism of the CNR1 gene with schizophrenia, it will serve as a good reference for future studies designed to examine the cannabinoid hypothesis of schizophrenia.