Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.
Apoptosis ; Autophagy* ; Caspase 3 ; Chloroquine ; Endothelial Cells* ; Fibroblast Growth Factor 2 ; Helminths ; Intercellular Signaling Peptides and Proteins ; Mebendazole* ; Microtubules ; Phosphorylation ; Phosphotransferases ; Receptors, Vascular Endothelial Growth Factor ; Vascular Endothelial Growth Factor A

BACKGROUND/AIMS: With improvements in the survival of liver transplantation (LT) recipients, the focus is shifting to patient quality of life (QOL), and employment is an important factor in aiding the social reintegration of LT patients. This study aims to evaluate the current employment status of liver graft recipients and various factors that may hinder reemployment. METHODS: Fifty patients above age 18 who underwent either living or deceased donor LT at a single center from March 2009 to July 2016 were interviewed during their visit to the outpatient clinic. The internally developed questionnaire consisted of 10 items. The Karnofsky Performance Scale and EQ-5D were used to evaluate patient function and QOL. RESULTS: A total of 25 (50%) patients returned to work after transplantation (the working group), and 21 (84%) patients in the working group returned to work within the first year after transplantation. In the non-working group (n=25), 17 (68%) answered that their health was the reason for unemployment. Fatigue and weakness were the most frequent symptoms. CONCLUSIONS: The data shows that as many as 50% of total patients returned to work after receiving LT. Fatigue and weakness were the most common complaints of the unemployed group, and resolving the causes of these symptoms may help to increase the employment rate.
Ambulatory Care Facilities ; Employment ; Fatigue* ; Humans ; Liver Transplantation* ; Liver* ; Quality of Life ; Tissue Donors ; Transplants ; Unemployment

Microbial colonization of the infant gut is unstable and shows a wide range of diversity between individuals. Gut microbiota play an important role in the development of the immune system, and an imbalance in these organisms can affect health, including an increased risk of allergic diseases. Microbial colonization of young infants is affected by the delivery mode at birth and the consequent alterations of gut microbiota in early life affect the development of allergic diseases. We investigated the effects of the delivery mode on the temporal dynamics of gut microbiota in healthy Korean infants. Fecal samples were collected at 1-3 days, 1 month, and 6 months after birth in six healthy infants. Microbiota were characterized by 16S rRNA shotgun sequencing. At the first and third days of life, infants born by vaginal delivery showed a higher richness and diversity of gut microbiota compared with those born by cesarean section. However, these differences disappeared with age. The Bacteroides genus and Bacteroidetes phylum were abundant in infants born by vaginal delivery, whereas Bacilli and Clostridium g4 were increased in infants born by cesarean section. The Firmicutes phylum and Bacteroides genus showed convergent dynamics with age. This study demonstrated the effect of delivery mode on the dynamics of gut microbiota profiles in healthy Korean infants.
Bacteroides ; Bacteroidetes ; Cesarean Section ; Clostridium ; Colon ; Female ; Firmicutes ; Gastrointestinal Microbiome* ; Humans ; Immune System ; Infant* ; Microbiota ; Parturition ; Pregnancy

BACKGROUND: Reactive oxygen species (ROS) and antioxidants are associated with maintenance of cellular function and metabolism. Nuclear factor-E2-related factor 1 (NFE2L1, Nrf1) is known to regulate the expression of a number of genes involved in oxidative stress and inflammation. The purpose of this study was to examine the effects of NFE2L1 on the response to oxidative stress in osteoblastic MC3T3-E1 cells. METHODS: The murine calvaria-derived MC3T3-E1 cell line was exposed to lipopolysaccharide (LPS) for oxidative stress induction. NFE2L1 effects were evaluated using small interfering RNA (siRNA) for NFE2L1 mRNA. ROS generation and the levels of known antioxidant enzyme genes were assayed. RESULTS: NFE2L1 expression was significantly increased 2.4-fold compared to the control group at 10 µg/mL LPS in MC3T3-E1 cells (P<0.05). LPS increased formation of intracellular ROS in MC3T3-E1 cells. NFE2L1 knockdown led to an additional increase of ROS (20%) in the group transfected with NFE2L1 siRNA compared with the control group under LPS stimulation (P<0.05). RNA interference of NFE2L1 suppressed the expression of antioxidant genes including metallothionein 2, glutamatecysteine ligase catalytic subunit, and glutathione peroxidase 1 in LPS-treated MC3T3-E1 cells. CONCLUSION: Our results suggest that NFE2L1 may have a distinct role in the regulation of antioxidant enzymes under inflammation-induced oxidative stress in MC3T3-E1 osteoblastic cells.
Antioxidants ; Catalytic Domain ; Cell Line ; Glutathione Peroxidase ; Inflammation ; Metabolism ; Metallothionein ; NF-E2-Related Factor 1 ; Osteoblasts* ; Oxidative Stress* ; Reactive Oxygen Species ; RNA Interference ; RNA, Messenger ; RNA, Small Interfering

PURPOSE: Development of a standardized guideline and assessment tool is necessary. Therefore, the aim is to investigate the current state of enteral feeding management and to develop a basis for a standardized guideline. METHODS: From July 1, 2010 through June 30, 2011, this study was conducted retrospectively for 100 patients who had enteral feeding more than once only in the Intensive Care Unit, after General Surgery at Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. The analysis was based on the following factors; age, diagnosis, name of the operation, period of start and the end of enteral feeding, method of injection, flushing method, residual volumes of the stomach, location and the size of the tube, medication through tubing, and complications related to enteral feeding. RESULTS: The mean age of the patients was 60.5, 65 men and 35 women. There were 30 malignant tumors of the hepatobiliary system and pancreas, 8 gastric and duodenal cancer, 4 colon and rectal cancer, 11 peritonitis, hemoperitoneum, and bowel obstruction, and 47 others. The average period of performing enteral feeding was 11.7 days and the locations of enteral feeding tube were stomach 56%, jejunum 39%, duodenum 3%, and undescribed 2%. The methods of enteral feeding were as follows; continuous feeding 19%, cyclic feeding 75%, intermittent and bolus feeding 3%, respectively. Only 1% of patients were on flushing and 16% on stomach residual. The most common complication of enteral feeding was clogging of the tube (5%). CONCLUSION: Due to the lack of detailed charting related to enteral feeding, we were unable to analyze the statistics on the relevance of complication which was the primary endpoint. As a result, development of a standardized protocol on charting enteral feeding is suggested for optimal enteral nutritional support.
Colon ; Diagnosis ; Duodenal Neoplasms ; Duodenum ; Enteral Nutrition* ; Female ; Flushing ; Hemoperitoneum ; Humans ; Intensive Care Units ; Jejunum ; Korea ; Male ; Nutritional Support ; Pancreas ; Peritonitis ; Rectal Neoplasms ; Residual Volume ; Retrospective Studies ; Seoul ; Stomach

The purpose of this study was to investigate the prevalence, clinical characteristics, and management of functional constipation at pediatric gastroenterology clinics. A prospective survey using the Rome III criteria was distributed to a group of parents of children with a constipation history and its control group in May 2008. The mean prevalence of constipation was 6.4%, which was similar to those in other countries. Statistically significant variables for children without constipation were that more children had a body mass index of below the 10th percentile even though they received more mother's care and ate balanced meals compared to the constipation group. Meanwhile, the constipation group frequently showed a history of constipation in infancy, picky-eating, lack of exercise, and retentive posturing. When analyzed with the Rome III criteria, the children showed greater than 60% rate of hard stools, painful stools, a history of large fecal mass in rectum, and its disappearance of constipation symptoms after passing a large stool. Our study found different approaches amongst pediatric gastroenterologists like rectal examinations, disimpaction, or drug treatment. Several factors addressed in our study can provide better guidelines for clinicians treating constipation and its future research.
Adolescent ; Body Mass Index ; Child ; Child, Preschool ; Constipation/*diagnosis/drug therapy/epidemiology ; Female ; Hospitals ; Humans ; Infant ; Laxatives/therapeutic use ; Male ; Prevalence ; Prospective Studies ; Rectum/physiopathology ; Severity of Illness Index

BACKGROUND/AIMS: The aim of this study was to compare polyethylene glycol (PEG) 4 L, split method of PEG 4 L and PEG 2 L plus sodium phosphate (NaP) in the aspect of bowel preparation quality, safety, patients' compliance and preference. METHODS: Total 249 subjects were prospectively enrolled and received bowel preparation for colonoscopy from August to October in 2010; PEG 4 L (93 subjects), split method of 4 L PEG (74 subjects) and PEG 2 L plus NaP 90 mL group (82 subjects). To investigate the completion, preference for bowel preparation and safety, a questionnaire survey was conducted before colonoscopy. RESULTS: There were no significant intergroup differences in the aspect of completion of preparation, cecal intubation time and success rate. Satisfaction and preference were higher in PEG 2 L plus NaP 90 mL and split method of 4 L PEG compared with PEG 4 L. In the aspect of the bowel preparation quality PEG 4 L showed significantly higher quality in the morning colonoscopy (p<0.001). However, in the afternoon colonoscopy PEG 2 L plus NaP 90 mL showed better result than PEG 4 L (p=0.009). Hyperphosphatemia was most frequently observed in PEG 2 L plus NaP 90 mL, but no severe adverse events occurred (p<0.001). CONCLUSIONS: PEG 4 L showed better result than split method of 4 L PEG or PEG 2 L plus NaP 90 mL in the aspect of bowel preparation quality and safety.
Adult ; Aged ; Cathartics/adverse effects/*pharmacology ; Colon/anatomy & histology/*drug effects ; Colonoscopy ; Female ; Humans ; Hyperphosphatemia/etiology ; Male ; Middle Aged ; Patient Compliance ; Phosphates/adverse effects/*pharmacology ; Polyethylene Glycols/adverse effects/*pharmacology ; Prospective Studies ; Questionnaires ; Time Factors

BACKGROUND: The aim of this study is to evaluate the status and adverse events of anesthesiologist-administered sedation and general anesthesia, outside of the operating room. METHODS: Patients undergoing sedation and general anesthesia, outside of the operating room, were retrospectively reviewed, during the study period from March to October of 2011. The patient's characteristics, primary diagnosis for the procedure, procedures performed outside of the operating room, adverse events associated with sedation and anesthesia, sedatives/anesthetic agents, and anesthetic time, were all assessed. RESULTS: A total of 429 patient's submitted data on 44 sedation/401 general anesthesia were encountered, during the study period. The range of age varied from 2 months to 83 yrs. Most common primary diagnosis for the procedure, during sedation or general anesthesia, was vascular or neurologic problem, respectively. The most frequently used sedatives or analgesics were propofol alone, during sedation (45%) and propofol with remifentanil, during general anesthesia (60%), respectively. Adverse events occurred in 32%, during sedation and 29%, during general anesthesia. Bradycardia occurred in 16% of sedation and hypotension occurred in 15% of general anesthesia. CONCLUSIONS: Our data suggest that the sedation/general anesthesia for procedures, outside of the operating room, have been performed in a complex situation, various location, and wide age groups. Adequate monitoring, sufficient anesthesia support, including skilled staff and emergency equipments, and appropriate drug for each procedure are needed for the patient's safety.
Analgesics ; Anesthesia ; Anesthesia, General ; Bradycardia ; Emergencies ; Humans ; Hypnotics and Sedatives ; Hypotension ; Operating Rooms ; Piperidines ; Propofol ; Retrospective Studies

Magnesium lithospermate B (MLB) is one of the major active components of Salvia miltiorrhizae. The anti-oxidative effects of Salvia miltiorrhizae have been previously reported. The aim of this study was to investigate the effect of purified MLB on hepatic fibrosis in rats and on the fibrogenic responses in hepatic stellate cells (HSCs). Hepatic fibrosis was induced in rats by intraperitoneal thioacetamide (TAA) injections over a period of 8 or 12 weeks. MLB was orally administered daily by gavage tube. Serum AST and ALT levels in TAA + MLB group were significantly lower than those in TAA only group at week 8. Hepatic fibrosis was significantly attenuated in TAA + MLB group than in TAA only group at week 8 or 12. Activation of HSCs was also decreased in TAA + MLB group as compared to TAA only group. Hepatic mRNA expression of alpha-smooth muscle actin (alpha-SMA), TGF-beta1, and collagen alpha1(I) was significantly decreased in TAA + MLB group as compared to TAA only group. Incubation with HSCs and MLB (> or =100 microM) for up to 48 h showed no cytotoxicity. MLB suppressed PDGF-induced HSC proliferation. MLB inhibited NF-kappaB transcriptional activation and monocyte chemotactic protein 1 (MCP-1) production in HSCs. MLB strongly suppressed H2O2-induced reactive oxygen species (ROS) generation in HSCs, and MLB inhibited type I collagen secretion in HSCs. We concluded that MLB has potent antifibrotic effect in TAA-treated cirrhotic rats, and inhibits fibrogenic responses in HSCs. These data suggest that MLB has potential as a novel therapy for hepatic fibrosis.
Actins/genetics/metabolism ; Animals ; Antioxidants/*administration & dosage ; Cell Proliferation/drug effects ; Collagen Type I/genetics/metabolism ; Drugs, Chinese Herbal/*administration & dosage ; Fibrosis/prevention & control ; Hepatic Stellate Cells/*drug effects/metabolism/pathology ; Liver/*drug effects/metabolism/pathology ; Liver Cirrhosis, Experimental/chemically induced/*drug therapy/physiopathology ; Male ; NF-kappa B/metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Salvia miltiorrhiza/immunology ; Thioacetamide/administration & dosage ; Transcriptional Activation/drug effects

PURPOSE: Breast reconstruction in patients who have undergone a mastectomy is performed less frequently in Korea than in Western countries. The aim of this study was to investigate the psychosocial problems related to a mastectomy and awareness of reconstruction after a mastectomy in breast cancer survivors. METHODS: From March to April 2010, 252 patients who underwent a mastectomy were recruited for this survey. The questionnaire included sociodemographic characteristics of patients, psychosocial problems related to mastectomy, and reasons not to receive breast reconstruction. RESULTS: Patients had difficulty going to a public bath (70.3%) or going to a swimming pool or the beach (74.6%). More than half of patients answered that their physical activity had decreased due to persistent shoulder or arm pain after the mastectomy. The most common psychological problem that patients experienced was distress over the loss of charm as a woman (66.8%), followed by considering themselves disabled (62.0%), and worries about recurrence (59.4%). The most common reason not to receive a breast reconstruction was the high cost of the operation (59.4%), followed by anxiety about complications (46.7%). Only 16.2% of patients reported that they did not receive enough information about reconstruction from their doctor. Of 229 patients, 43.7% would consider undergoing breast reconstruction in the future. CONCLUSION: Breast cancer survivors who underwent a mastectomy suffered from various psychosocial problems, and high cost was a major reason for not undergoing breast reconstruction. Broader health insurance coverage should be provided for breast reconstruction in breast cancer survivors.
Female ; Humans ; Breast Neoplasms