Licochalcone H Induces Cell Cycle Arrest and Apoptosis in Human Skin Cancer Cells by Modulating JAK2/STAT3 Signaling

Licochalcone H (LCH) is a phenolic compound synthetically derived from licochalcone C (LCC) that exerts anticancer activity. In this study, we investigated the anticancer activity of LCH in human skin cancer A375 and A431 cells. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cell viability assay was used to evaluate the antiproliferative activity of LCH. Cell cycle distribution and the induction of apoptosis were analyzed by flow cytometry. Western blotting assays were performed to detect the levels of proteins involved in cell cycle progression, apoptosis, and the JAK2/STAT3 signaling pathway. LCH inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay revealed that LCH induced apoptosis, and the LCH-induced apoptosis was accompanied by cell cycle arrest in the G1 phase. Western blot analysis showed that the phosphorylation of JAK2 and STAT3 was decreased by treatment with LCH. The inhibition of the JAK2/STAT3 signaling pathway by pharmacological inhibitors against JAK2/STAT3 (cryptotanshinone (CTS) and S3I-201) simulated the antiproliferative effect of LCH suggesting that LCH induced apoptosis by modulating JAK2/STAT3 signaling.

Podophyllotoxin Induces ROS-Mediated Apoptosis and Cell Cycle Arrest in Human Colorectal Cancer Cells via p38 MAPK Signaling

Podophyllotoxin (PT), a lignan compound from the roots and rhizomes of Podophyllum peltatum, has diverse pharmacological activities including anticancer effect in several types of cancer. The molecular mechanism of the anticancer effects of PT on colorectal cancer cells has not been reported yet. In this study, we sought to evaluate the anticancer effect of PT on human colorectal cancer HCT116 cells and identify the detailed molecular mechanism. PT inhibited the growth of cells and colony formation in a concentration-dependent manner and induced apoptosis as determined by the annexin V/7-aminoactinomycin D double staining assay. PT-induced apoptosis was accompanied by cell cycle arrest in the G2/M phase and an increase in the generation of reactive oxygen species (ROS). The effects of PT on the induction of ROS and apoptosis were prevented by pretreatment with N-acetyl-L-cysteine (NAC), indicating that an increase in ROS generation mediates the apoptosis of HCT116 cells induced by PT.Furthermore, Western blot analysis showed that PT upregulated the level of phospho (p)-p38 mitogen-activated protein kinase (MAPK). The treatment of SB203580, a p38 inhibitor, strongly prevented the apoptosis induced by PT, suggesting that PT-induced apoptosis involved the p38 MAPK signaling pathway. In addition, PT induced the loss of mitochondrial membrane potential and multi-caspase activation. The results suggested that PT induced cell cycle arrest in the G2/M phase and apoptosis through the p38 MAPK signaling pathway by upregulating ROS in HCT116 cells.

Indication and Clinical Outcomes of Percutaneous Endoscopic Gastrostomy: A Single-center Retrospective Analysis

BACKGROUND/AIMS: Percutaneous endoscopic gastrostomy (PEG) is performed to provide enteral nutrition to patients who require tube-feeding support due to impaired oral intake. As life expectancy increases, the need for, and use of PEG also tend to increase. We aimed to evaluate the indications and complications of PEG insertion, and to investigate any differences in the complication group. MATERIALS AND METHODS: We conducted a retrospective analysis of 109 patients who received a PEG procedure between April 2011 and April 2016 in the Korea University Ansan Hospital. We reviewed the indications and complications related to PEG insertion and time interval of tube change. RESULTS: Among 109 patients who underwent a PEG procedure, 71.6% were male, and the mean age was 68.2 years. The most common indications for PEG were central nervous system diseases, including stroke (33.9%), cerebral hemorrhage (29.4%), and hypoxic brain damage (8.3%). The overall complication rate was 14.7%, and the most common complication was peristomal infection (7.3%). Most of the complications occurred within 10 days in 14 of 16 patients (87.5%). The patients with complications were older than those without complications (74.6±11.1 vs. 67.1±14.0 years, P=0.043). The mean time interval for gastrostomy tube change was 7.3 months. CONCLUSIONS: The most common indication of PEG was brain disease, and the complication rate cannot be ignored. Careful attention is needed after a PEG procedure especially in elderly patients.

Factors Influencing Nursing Students' Performance on Standard Precautions of Infection Control

PURPOSE: The purpose of this study was to identify the factors that affect nursing students' performance on standard precaution of infection control. METHODS: For the analysis of the study results, mistakes and percentages, descriptive statistics, Pearson's coefficient, and multiple regression analysis were performed. RESULTS: Among the participants, 76.5% received hospital infection education, and 72.5% experienced an exposure to blood or body fluid, and the most of the exposures were occurred during the first semester of the third year. The knowledge score was 20.08±2.09, the awareness score was 4.63±.41, and the performance score was 4.34±.55. In the relationship between the standard precautions knowledge, awareness, and performance, the awareness and the performance were in positive correlations, while the factors that affected the performance level of the standard precautions were awareness and the school year (third year), which had 37.0% of the total exposures. CONCLUSION: In order to increase the performance level of the standard precautions among the nursing department students, after identifying the differences between school years and demands of the students, it is necessary to provide continuous and regular education of standard precautions.

Metastatic papillary thyroid cancers with malignant pleural effusion aggravated during thyroid hormone withdrawal for radioiodine therapy / 영남의대학술지

L-thyroxine (LT4) withdrawal prior to radioactive iodine (RAI) ablation therapy is a commonly used method for successful treatment of patients with papillary thyroid cancer (PTC). However, a prolonged period of hypothyroidism induced by LT4 withdrawal is sometimes associated with impaired quality of life and cardiopulmonary dysfunction in PTC patients. Furthermore, LT4 withdrawal may have a trophic effect on residual cancer by means of increased thyrotropin. We report on 2 cases of metastatic PTC patients with malignant pleural effusion (MPE) whose disease showed rapid worsening after LT4 withdrawal and RAI therapy. The first case is a 65-year-old woman who had PTC with multiple distant metastases and MPE. During LT4 withdrawal for RAI therapy, MPE showed rapid worsening, and the patient required repetitive therapeutic thoracentesis. The second case is a 49-year-old woman with PTC who underwent 3 additional operations for cancer recurrence in the neck lymph nodes and 6 times of RAI treatments. While preparing for the 7th RAI treatment by withdrawing LT4, she developed MPE which became progressively aggravated after RAI therapy. Both patients experienced increased pleural effusion during the LT4 withdrawal period and a rise in the thyroglobulin level was observed after RAI therapy. MPE was not controlled with therapeutic thoracentesis and pleurodesis. Eventually, both patients died of rapid disease progression after RAI therapy. In summary, LT4 withdrawal may have an adverse effect on metastatic PTC patients, particularly those with MPE.

EEG Source Imaging in Partial Epilepsy in Comparison with Presurgical Evaluation and Magnetoencephalography

BACKGROUND AND PURPOSE: The aim of this study was to determine the usefulness of three-dimensional (3D) scalp EEG source imaging (ESI) in partial epilepsy in comparison with the results of presurgical evaluation, magnetoencephalography (MEG), and electrocorticography (ECoG). METHODS: The epilepsy syndrome of 27 partial epilepsy patients was determined by presurgical evaluations. EEG recordings were made using 70 scalp electrodes, and the 3D coordinates of the electrodes were digitized. ESI images of individual and averaged spikes were analyzed by Curry software with a boundary element method. MEG and ECoG were performed in 23 and 9 patients, respectively. RESULTS: ESI and MEG source imaging (MSI) results were well concordant with the results of presurgical evaluations (in 96.3% and 100% cases for ESI and MSI, respectively) at the lobar level. However, there were no spikes in the MEG recordings of three patients. The ESI results were well concordant with MSI results in 90.0% of cases. Compared to ECoG, the ESI results tended to be localized deeper than the cortex, whereas the MSI results were generally localized on the cortical surface. ESI was well concordant with ECoG in 8 of 9 (88.9%) cases, and MSI was also well concordant with ECoG in 4 of 5 (80.0%) cases. The EEG single dipoles in one patient with mesial temporal lobe epilepsy were tightly clustered with the averaged dipole when a 3 Hz high-pass filter was used. CONCLUSIONS: The ESI results were well concordant with the results of the presurgical evaluation, MSI, and ECoG. The ESI analysis was found to be useful for localizing the seizure focus and is recommended for the presurgical evaluation of intractable epilepsy patients.

Leflunomide-induced Toxic Epidermal Necrolysis in a Patient with Rheumatoid Arthritis

Leflunomide was licensed for the treatment of rheumatoid arthritis in 1998 and has been available in Korea since 2003. Allergic cutaneous reactions (rash, purpura) are common (<10%) side effects of leflunomide, but severe cases such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) are rarely reported. There has not been a report of SJS or TEN induced by leflunomide in Korea. Here we report a case of leflunomide-induced TEN in a patient with rheumatoid arthritis. Leflunomide was discontinued, and the TEN was treated with methylprednisolone, cholestyramine and immunoglobulin. The skin lesion eventually resolved over four weeks with residual post-inflammatory hyperpigmentation.

Mutiple Spontaneous Rib Fractures in Patient with Cushing's Syndrome

Glucocorticoid (GC) excess, including Cushing's syndrome, is a common cause of secondary osteoporosis. Thirty to fifty percent of Cushing's syndrome patients experience non-traumatic fractures, which is often the presenting manifestation of Cushing's syndrome. However, there have been rare cases of Cushing's syndrome diagnosed only based upon bone manifestations. We describe a case of Cushing's syndrome that was diagnosed in a 44-year-old woman who initially visited our hospital due to multiple non-traumatic rib fractures. She did not exhibit any other manifestations of Cushing's syndrome such as moon face, buffalo hump or abdominal striae. Initially, we evaluated her for bone metastases from a cancer of unknown origin, but there was no evidence of metastatic cancer. Instead, we found a left adrenal incidentaloma. As a result of the hormone study, she was diagnosed as having Cushing's syndrome. Interestingly, her bony manifestation of Cushing's syndrome, which was evident in the bone scan and bone mineral densitometry, completely recovered after a left adrenalectomy. Therefore, the possibility of Cushing's syndrome as a cause of secondary osteoporosis should be considered in young patients with non-traumatic multiple fractures, with or without any other typical features of Cushing's syndrome.

Mycotic Aneurysm of the Aortic Arch / 대한구급학회지

A mycotic aneurysm of the thoracic aorta is rare. We report a case of mycotic aneurysm that developed in the aortic arch. An 86-year-old man was admitted with fever and general weakness. Blood culture yielded methicillin-resistant Staphylococcus aureus. Chest X-ray showed an enlarged aortic arch, and computed tomography scan revealed an aneurysm in the aortic arch. The patient was treated only with antibiotics and not surgically. The size of the aneurysm increased rapidly, resulting in bronchial obstruction and superimposed pneumonia. The patient died of respiratory failure.

Obsessive-Compulsive Symptoms and Their Impacts on Psychosocial Functioning in People with Epilepsy

BACKGROUND AND PURPOSE: Obsessive-compulsive symptoms (OCS) in people with epilepsy (PWE) have not been studied systematically. We evaluated the severity, predictors, and psychosocial impact of OCS in PWE. METHODS: We recruited PWE who visited our epilepsy clinic and age-, gender-, and education-matched healthy controls. Both PWE and healthy controls completed the Maudsley Obsessional-Compulsive Inventory (MOCI), which measures OCS. PWE also completed the Beck Depression Inventory (BDI) and the Quality of Life in Epilepsy Inventory-31 (QOLIE-31). We examined the severity of OCS in PWE relative to healthy controls. Predictors of OCS and the QOLIE-31 score were measured by regression analyses. A path analysis model was constructed to verify interrelations between the variables. RESULTS: The MOCI total score was significantly higher in PWE than in healthy controls (p=0.002). OCS were found in 20% of eligible patients. The strongest predictor of the MOCI total score was the BDI score (beta=0.417, p<0.001), followed by EEG abnormality (beta=0.194, p<0.001) and etiology (beta=0.107, p=0.031). Epileptic syndrome, the side of the epileptic focus, and action mechanisms of antiepileptic drugs did not affect the MOCI total score. The strongest predictor of the QOLIE-31 overall score was the BDI score (beta=-0.569, p<0.001), followed by seizure control (beta=-0.163, p<0.001) and the MOCI total score (beta=-0.148, p=0.001). The MOCI total score directly affected the QOLIE-31 overall score and also exerted indirect effects on the QOLIE-31 overall score through seizure control and the BDI score. CONCLUSIONS: OCS are more likely to develop in PWE than in healthy people. The development of OCS appears to elicit psychosocial problems directly or indirectly by provoking depression or uncontrolled seizures.

An Imported Case of Severe Falciparum Malaria with Prolonged Hemolytic Anemia Clinically Mimicking a Coinfection with Babesiosis

While imported falciparum malaria has been increasingly reported in recent years in Korea, clinicians have difficulties in making a clinical diagnosis as well as in having accessibility to effective anti-malarial agents. Here we describe an unusual case of imported falciparum malaria with severe hemolytic anemia lasting over 2 weeks, clinically mimicking a coinfection with babesiosis. A 48-year old Korean man was diagnosed with severe falciparum malaria in France after traveling to the Republic of Benin, West Africa. He received a 1-day course of intravenous artesunate and a 7-day course of Malarone (atovaquone/proguanil) with supportive hemodialysis. Coming back to Korea 5 days after discharge, he was readmitted due to recurrent fever, and further treated with Malarone for 3 days. Both the peripheral blood smears and PCR test were positive for Plasmodium falciparum. However, he had prolonged severe hemolytic anemia (Hb 5.6 g/dl). Therefore, 10 days after the hospitalization, Babesia was considered to be potentially coinfected. A 7-day course of Malarone and azithromycin was empirically started. He became afebrile within 3 days of this babesiosis treatment, and hemolytic anemia profiles began to improve at the completion of the treatment. He has remained stable since his discharge. Unexpectedly, the PCR assays failed to detect DNA of Babesia spp. from blood. In addition, during the retrospective review of the case, the artesunate-induced delayed hemolytic anemia was considered as an alternative cause of the unexplained hemolytic anemia.

Co-Occurrence of Syringomyelia and Hydrocephalus in a Patient Without Chiari Malformation in Her 50's

Syringomyelia rarely accompanies hydrocephalus in the aged person except for the cases with a typical Chiari malformation. A 59-year-old woman developed progressive generalized weakness and gait disturbance for 9 years. MRI demonstrated marked enlargement of the cerebral ventricles and the longitudinal dilatation of central canal involving the entire spinal cord, whereas a typical Chiari malformation was absent. She was successfully treated by ventriculoperitoneal shunting. We report a hydrocephalic patient in her 50's accompanied by syringomyelia without a typical Chiari malformation.

Spontaneous Downbeat Nystagmus in Metronidazole-Induced Encephlaopathy

No abstract available.

Pancytopenia Associated with Mycoplasma pneumoniae Pneumonia / 소아알레르기및호흡기학회지

Mycoplasma pneumoniae is the most common pathogen of the respiratory tract among school-aged children and adolescents. It can also cause extrapulmonary manifestation that involves the skin, nervous system, digestive system, and hematopoietic system. A 12-year old girl was admitted to Asan Medical Center Children's Hospital with M. pneumoniae pneumonia. Her respiratory symptoms and signs improved after the treatment with macrolide antibiotics, and she was discharged. However, pancytopenia developed 16 days after the first admission date. She was readmitted, and treated successfully with intravenous immunoglobulin. We reported her as the first case of pancytopenia asscociated with M. pnuemoniae pneumonia in Korea.

Gitelman Syndrome with Normal Serum Magnesium

Gitelman syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemic metabolic alkalosis, and it is distinguished from Batter syndrome by hypomagnesemia and hypocalciuria. This disorder is caused by mutation in SLC12A3 gene which encodes thiazide-sensitive Na(+)-Cl(-)cotransporter (NCCT) which is expressed in the apical membrane of cells, lining distal convoluted tubule. A 8-year old boy who presented with Rolandic epilepsy, and horseshoe kidney accidentally showed clinical features of metabolic alkalosis, hypokalemia, hypocalciuria without hypomagnesemia. So we identified a heterozygote mutation and an abnormal splicing in the SLC12A3 gene, encoding NCCT. The mutation was detected in the exon 15 and 22 of SLC12A3 gene.

Diagnosis of Incomplete Kawasaki Disease in Infants Based on an Inflammation at the Bacille Calmette-Guerin Inoculation Site

BACKGROUND AND OBJECTIVES: This study was intended to test how the inflammation at the Bacille Calmette-Guerin (BCG) inoculation site (BCGitis) can be a useful a diagnostic feature of Kawasaki disease (KD). SUBJECTS AND METHODS: All subjects were infants at the time of admission, and had received BCG vaccination during their neonatal period. There were 54 patients with complete KD (group 1) and 29 patients with incomplete KD (group 2). All 83 patients had BCGitis during the acute phase of illness. Data regarding the coronary artery diameters in 31 age-matched controls were used for comparison. RESULTS: The 2 patient groups did not differ in clinical and laboratory variables. During the acute phase, the median z scores of the left anterior descending coronary artery (LAD) diameter were 0.20, 0.42, and -0.48 in groups 1, 2, and control respectively, and that of right coronary artery (RCA) diameters were -0.15, -0.16, and -1.17 respectively. The z scores in both patient groups were greater than those in controls (p=0.0014 in LAD and p<0.0001 in RCA between group 1 and controls; p=0.0023 in LAD and p<0.0001 in RCA between group 2 and controls). A similar pattern was observed during the subacute and convalescent phases. CONCLUSION: BCGitis is a useful feature in the diagnosis of incomplete KD in infants who received BCG vaccine during neonatal period.

Effect of Pertussis Toxin and Herbimycin A on Proteinase-Activated Receptor 2-Mediated Cyclooxygenase 2 Expression in Helicobacter pylori-Infected Gastric Epithelial AGS Cells

Helicobacter pylori (H. pylori) is an important risk factor for chronic gastritis, peptic ulcer, and gastric cancer. Proteinase-activated receptor 2 (PAR2), subgroup of G-protein coupled receptor family, is highly expressed in gastric cancer, and chronic expression of cyclooxygenase-2 (COX-2) plays an important role in H. pylori-associated gastric carcinogenesis and inflammation. We previously demonstrated that H. pylori induced the expression of PAR2 and COX-2 in gastric epithelial cells. Present study aims to investigate whether COX-2 expression induced by H. pylori in Korean isolates is mediated by PAR2 via activation of Gi protein and Src kinase in gastric epithelial AGS cells. Results showed that H. pylori-induced COX-2 expression was inhibited in the cells transfected with antisense oligonucleotide for PAR2 or treated with Gi protein blocker pertussis toxin, Src kinase inhibitor herbimycin A and soybean trypsin inbitor, indicating that COX-2 expression is mediated by PAR2 through activation of Gi protein and Src kinase in gastric epithelial cells infected with H. pylori in Korean isolates. Thus, targeting the activation of PAR2 may be beneficial for prevention or treatment of gastric inflammation and carcinogenesis associated with H. pylori infection.

Relations among Depression, Life Satisfaction and Health Promoting Behavior in the Elderly

PURPOSE: The purposes of this study were to examine the relations among depression, life satisfaction and health promoting behavior, and to find factors related with health promoting behavior. METHODS: The subjects were 198 elderly people of over 65 living in K City and S City. Data were collected through a structured questionnaire and analyzed by SPSS/WIN 13.0. RESULTS: Health promoting behavior was significantly different according to religion, education level, living with family, previous job, pocket money, subjectively economic level, and leisure activities. Depression was significantly different according to education level, living with family, pocket money, economic level, and leisure activities. And life satisfaction was significantly different according to religion, living with family, and pocket money. The variables that affected the degree of health promoting behavior were depression, life satisfaction and living with family, and they represented 29.7% of health promoting behavior. CONCLUSION: The health promoting behavior of the subjects was better than average and, at the same time, the lower depression in the health promoting behavior was the higher life satisfaction was. Therefore, in order to decrease depression and to increase life satisfaction, the development of advanced health promoting programs will be helpful to lead health life for the elderly people.

Membrane Proteome Analysis of Cerulein-Stimulated Pancreatic Acinar Cells: Implication for Early Event of Acute Pancreatitis

BACKGROUND/AIMS: Cerulein pancreatitis is similar to human edematous pancreatitis with dysregulation of the production and secretion of digestive enzymes, edema formation, cytoplasmic vacuolization and the death of acinar cells. We hypothesized that membrane proteins may be altered as the early event during the induction of acute pancreatitis. Present study aims to determine the differentially expressed proteins in the membranes of cerulein-treated pancreatic acinar cells. METHODS: Pancreatic acinar AR42J cells were treated with 10(-8) M cerulein for 1 hour. Membrane proteins were isolated from the cells and separated by two-dimensional electrophoresis using pH gradients of 5-8. Membrane proteins were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the peptide digests. The differentially expressed proteins, whose expression levels were more or less than three-fold in cerulein-treated cells, were analyzed. RESULTS: Two differentially expressed proteins (mannan-binding lectin-associated serine protease-2, heat shock protein 60) were up-regulated while four proteins (protein disulfide isomerase, gamma-actin, isocitrate dehydrogenase 3, seven in absentia homolog 1A) were down-regulated by cerulein treatment in pancreatic acinar cells. These proteins are related to cell signaling, oxidative stress, and cytoskeleton arrangement. CONCLUSIONS: Oxidative stress may induce cerulein-induced cell injury and disturbances in defense mechanism in pancreatic acinar cells.

Lysophosphatidic acid receptor 2 and Gi/Src pathway mediate cell motility through cyclooxygenase 2 expression in CAOV-3 ovarian cancer cells

Lysophosphatidic acid (LPA) is a bioactive phospholipids and involves in various cellular events, including tumor cell migration. In the present study, we investigated LPA receptor and its transactivation to EGFR for cyclooxygenase-2 (COX-2) expression and cell migration in CAOV-3 ovarian cancer cells. LPA induced COX-2 expression in a dose-dependent manner, and pretreatment of the cells with pharmacological inhibitors of Gi (pertussis toxin), Src (PP2), EGF receptor (EGFR) (AG1478), ERK (PD98059) significantly inhibited LPA- induced COX-2 expression. Consistent to these results, transfection of the cells with selective Src siRNA attenuated COX-2 expression by LPA. LPA stimulated CAOV-3 cell migration that was abrogated by pharmacological inhibitors and antibody of EP2. Higher expression of LPA2 mRNA was observed in CAOV-3 cells, and transfection of the cells with a selective LPA2 siRNA significantly inhibited LPA-induced activation of EGFR and ERK, as well as COX-2 expression. Importantly, LPA2 siRNA also blocked LPA-induced ovarian cancer cell migration. Collectively, our results clearly show the significance of LPA2 and Gi/Src pathway for LPA-induced COX-2 expression and cell migration that could be a promising drug target for ovarian cancer cell metastasis.