Effect of Trimebutine and Rifaximin on Breath Hydrogen and Methane by Glucose Breath Test in Patients With Functional Bloating: A Randomized Double-blind Clinical Trial

Background/Aims@#Drugs that stabilize intestinal motility may improve the efficacy of nonabsorbable antibiotics, such as rifaximin, against small intestinal bacterial overgrowth (SIBO). We compared the efficacy of rifaximin alone with that of its combination with trimebutine maleate against SIBO. @*Methods@#We performed a randomized double-blind placebo-controlled trial (https://cris.nih.go.kr, no. KCT0004836) that included patients with functional bloating, no constipation, and SIBO using the hydrogen (H2 )–methane (CH4 ) glucose breath test (GBT). Patients were randomized into 2 groups in a 1:1 ratio, namely rifaximin (1200 mg/day) + trimebutine maleate (600 mg/day) group and rifaximin + placebo group, for 2 weeks. Patients completed a symptom questionnaire and underwent a GBT at baseline and at 1 month after treatment withdrawal. The primary outcome was SIBO eradication. The secondary outcomes included changes in the concentrations of exhaled gases, symptoms, and presence of adverse events. @*Results@#The complete eradication rate of SIBO was 35.9% (14/39) in the rifaximin group, and 34.1% (14/41) in the combined group with no significant differences. In both groups, no significant differences were observed in GBT profiles before and after the treatment, respectively. However total breath H2 and CH4 concentration were conspicuously decreased in the combined group after treatment.The combined group exhibited substantial relief of bloating. The adverse events were similar in the 2 groups. @*Conclusion@#While the combination therapy was not superior over rifaximin alone for SIBO eradication, it improves the symptom of bloating with numerically reducing the concentration of breath H2 /CH4 .

Lactase Deficiency Diagnosed by Endoscopic Biopsy-based Method is Associated With Positivity to Glucose Breath Test

Background/Aims@#Lactase deficiency, which has many similarities with small intestinal bacterial overgrowth (SIBO), causes various gastrointestinal symptoms. We estimate the prevalence of SIBO in patients with intestinal symptoms from dairy products and investigate the association between lactase deficiency (LD) and SIBO. @*Methods@#This prospective study included patients with functional intestinal symptoms from dairy product indigestion. A questionnaire on gastrointestinal symptoms, a hydrogen (H 2 )-methane glucose breath test (GBT) for SIBO, and lactose intolerance quick test (LQT) for LD using upper gastrointestinal endoscopy were performed. @*Results@#A total of 88 patients, 29 (33.0%) with severe and 36 (40.9%) with mild LD were included. Sixteen patients (18.2%) were GBT positive. Patients with LQT negativity indicating severe LD showed a higher positivity to GBT or GBT (H 2 ) than the historic controls (27.6% vs 6.7%, P = 0.032). There was no difference in the items on the symptom questionnaire according to the presence of LD or SIBO, except for higher symptom scores for urgency in GBT-positive patients. There were more LQT-negative patients in the GBT (H 2 )-positive group than in the other groups (27.6% vs 10.2%, P = 0.036). Moreover, only GBT (H 2 )-positivity was significantly associated with a higher risk of LQT negativity in multivariate analysis (OR, 4.19; P = 0.029). @*Conclusions@#SIBO producing H 2is common in patients with severe LD suspected lactose intolerance. SIBO may be a new therapeutic target for managing intestinal symptoms in patients with lactose intolerance.

Comparing the Expression of Canonical and Non-Canonical Inflammasomes Across Glioma Grades: Evaluating Their Potential as an Aggressiveness Marker

Background@#Inflammasomes are key in the initiation of inflammatory responses and serve to de-fend the organism. However, when the immune system is imbalanced, these complexes contribute to tumor progression. The purpose of this study was to investigate the effect of non-canonical inflammasomes on glioma malignancy. @*Methods@#We performed bioinformatics analysis to confirm the expression of canonical andnon-canonical inflammasome-related molecules according to the degree of malignancy through immunohistochemical examination of glioma tissues obtained with patient consent from our institution. @*Results@#Bioinformatics analysis confirmed that the expression levels of non-canonical inflam-masome-related molecules were significantly higher in tumor tissues than in normal tissues, and they also increased according to malignancy, which adversely affected the survival rate. Furthermore, in gliomas, positive correlations were found between N-form gasdermin-D, a key molecule associated with the non-canonical inflammasome, and other related molecules, including NLRP3, caspase-1, caspase-4, and caspase-5. These results were verified by immunohistochemical examination of glioma tissues, and the expression levels of these molecules also increased significantly with increasing grade.In addition, the features of pyroptosis were confirmed. @*Conclusion@#This study identified the potential of non-canonical inflammasomes as aggressiveness markers for gliomas and presented a perspective for improving glioma treatment.

Oral Sulfate Solution Is as Effective as Polyethylene Glycol with Ascorbic Acid in a Split Method for Bowel Preparation in Patients with Inactive Ulcerative Colitis: A Randomized, Multicenter, and Single-Blind Clinical Trial

Background/Aims@#Low-volume preparations for colonoscopy are gaining attention for their higher acceptability. However, the efficacy and safety of oral sulfate solution (OSS) preparations in patients with ulcerative colitis (UC) has not been well known. Therefore, we aimed to compare OSS and 2-L polyethylene glycol with ascorbic acid (PEG+Asc) for bowel preparation in inactive UC. @*Methods@#A multicenter, randomized, single-blind study was conducted at six tertiary referral hospitals in Korea. Outpatients with UC who had stable disease activity were randomly allocated to the OSS group or the 2-L PEG+Asc group for bowel preparation before colonoscopy. The study outcomes included treatment efficacy, safety, tolerability, and acceptability. Bowel cleansing was assessed using the Boston Bowel Preparation Scale and rated as successful cleansing if the score was ≥6. Patient acceptance and tolerability were assessed using a 4-point ordinal scale. Additionally, disease activity and laboratory data before and after colonoscopy were evaluated to check for safety. @*Results@#The OSS and 2-L PEG+Asc groups included 92 and 93 participants, respectively. No significant between-group difference was noted in successful cleansing (OSS [96.7%] vs 2-L PEG+Asc [97.8%], p=0.64). Moreover, the safety, acceptance, and tolerability were not significantly different (all p>0.05). Furthermore, no significant changes were found in serum electrolytes or disease activity in either group. @*Conclusions@#OSS is effective for colonoscopy cleansing, has acceptable tolerability, and does not affect disease activity; thus, it can be used safely for bowel preparation in patients with inactive UC.

Incidence, Morbidity, and Mortality of Achalasia: A Nationwide, Population-Based Cohort Study in South Korea

Background/Aims@#Although an association between achalasia and esophageal cancer has been reported, whether achalasia confers a substantial increase in mortality is unknown. Moreover, the causes of death related to achalasia have not been investigated. We performed this nationwide, population-based cohort study on achalasia because no such study has been performed since the introduction of high-resolution manometry in 2008. @*Methods@#This study was performed using data extracted from the Korean National Health Insurance Service database, covering a 9-year period from 2009 to 2017. Control participants without a diagnostic code for achalasia were randomly selected and matched by sex and birth year at a case-to-control ratio of 1:4. Data on the cause of death from Statistics Korea were also analyzed. @*Results@#The overall incidence of achalasia was 0.68 per 100,000 person-years, and the prevalence was 6.46 per 100,000 population. Patients with achalasia (n=3,063) had significantly higher adjusted hazard ratio (aHR) for esophageal cancer (aHR, 3.40; 95% confidence interval [CI], 1.25 to 9.22; p=0.017), pneumonia (aHR, 2.30; 95% CI, 1.89 to 2.81; p<0.001), aspiration pneumonia (aHR, 3.92; 95% CI, 2.38 to 6.48; p<0.001), and mortality (aHR, 1.68; 95% CI, 1.44 to 1.94; p<0.001). Esophageal cancer carried the highest mortality risk (aHR, 8.82; 95% CI, 2.35 to 33.16; p=0.001), while pneumonia had the highest non-cancer mortality risk (aHR, 2.28; 95% CI, 1.31 to 3.96; p=0.004). @*Conclusions@#In this nationwide study, achalasia was associated with increased risk of mortality.Esophageal cancer and pneumonia were the most common comorbidities and the major causes of death in patients with achalasia.

Fracture Risk in Middle-Aged and Older Patients With Inflammatory Bowel Disease: A Korean Nationwide Population-Based Cohort Study

Background@#Fracture risks and associated factors are poorly understood in middle-aged and older Asian populations with inflammatory bowel disease (IBD). Therefore, we investigated fracture risk and the effects of comorbidities and lifestyle habits on the risk of developing fractures in middle-aged and older Korean patients with IBD. @*Methods@#We conducted a nationwide population-based cohort study using data from the National Health Insurance Corporation Database. Patients with IBD who underwent the National Screening Program and were over 40 years of age were included in the study. We compared patients with age- and sex-matched controls. The incidence of fractures, including vertebral, hip, and other sites, was determined using claims data. @*Results@#The risk of total fractures and vertebral fractures was significantly higher in the IBD group (adjusted hazard ratio [HR], 1.31, 95% confidence interval [CI], 1.16–1.48; adjusted HR, 1.59, 95% CI, 1.33–1.92, respectively). Obesity, diabetes, hypertension, and lack of exercise were associated with increased fracture risk in patients with ulcerative colitis (UC). In contrast, the risk increases in patients with Crohn’s disease regardless of comorbidities and lifestyle preferences. @*Conclusion@#The risk of bone fracture, especially vertebral fracture, is high in middle-aged and older Korean patients with IBD. Obesity, diabetes, hypertension, and lack of exercise are all risk factors associated with bone fractures in patients with UC. These findings are helpful for clinicians to educate patients with IBD on bone health and raise awareness of bone fractures in patients with UC who have specific risk factors.

Role of Glucose Breath Test for Small Intestinal Bacterial Overgrowth in Children and Adolescents With Functional Abdominal Pain Disorders in Korea

Background/Aims@#Small intestinal bacterial overgrowth (SIBO) is expected in children and adolescents with functional abdominal pain disorders (FAPDs). This study is conducted to estimate the prevalence of SIBO and to investigate the role of SIBO in children and adolescents with FAPDs. @*Methods@#This prospective study enrolled children with FAPDs fulfilling the Rome IV criteria. A hydrogen-methane glucose breath test was used to diagnose SIBO. A survey of bowel symptoms using questionnaires, birth history, types of feeding, and the presence of allergy was conducted. @*Results@#Sixty-eight children and adolescents (range, 6-17 years; median, 12.5 years) were enrolled. SIBO was detected in 14 patients (20.6%). Age (≥ 12 years) (P < 0.003) and loose stool (P = 0.048) were significantly more common in children with SIBO than in children without SIBO. However, the history of allergies (P = 0.031) was less common in children with SIBO than those without SIBO. No significant differences were observed in other demographic findings. In multivariate analysis, age (≥ 12 years) was the independent factor predicting SIBO in children with FAPDs. @*Conclusions@#SIBO is not uncommon in children and adolescents with FAPDs. Among children aged above 12 years and diagnosed with FAPDs, SIBO is a suspected clinical target for treatment to relieve intestinal symptoms. A further study to investigate the association between intestinal bacteria and history of allergy is needed.

Clinical Course of Hepatitis B Viral Infection in Patients Undergoing Anti-Tumor Necrosis Factor α Therapy for Inflammatory Bowel Disease

Background/Aims@#Little is known about the clinical course of hepatitis B virus (HBV)-infected patients undergoing anti-tumor necrosis factor α (TNF-α) therapy for inflammatory bowel disease (IBD). We aimed to investigate the clinical course of HBV infection and IBD and to analyze liver dysfunction risks in patients undergoing anti-TNF-α therapy. @*Methods@#This retrospective multinational study involved multiple centers in Korea, China, Tai-wan, and Japan. We enrolled IBD patients with chronic or resolved HBV infection, who received anti-TNF-α therapy. The patients’ medical records were reviewed, and data were collected using a web-based case report form. @*Results@#Overall, 191 patients (77 ulcerative colitis and 114 Crohn’s disease) were included, 28.3% of whom received prophylactic antivirals. During a median follow-up duration of 32.4 months, 7.3% of patients experienced liver dysfunction due to HBV reactivation. Among patients with chronic HBV infection, the proportion experiencing liver dysfunction was significantly higher in the non-prophylaxis group (26% vs 8%, p=0.02). Liver dysfunction occurred in one patient with resolved HBV infection. Antiviral prophylaxis was independently associated with an 84% reduction in liver dysfunction risk in patients with chronic HBV infection (odds ratio, 0.16; 95% confidence interval, 0.04 to 0.66; p=0.01). The clinical course of IBD was not associated with liver dysfunction or the administration of antiviral prophylaxis. @*Conclusions@#Liver dysfunction due to HBV reactivation can occur in HBV-infected IBD patients treated with anti-TNF-α agents. Careful monitoring is needed in these patients, and antivirals should be administered, especially to those with chronic HBV infection.

Primary Tumor Suppression and Systemic Immune Activation of Macrophages through the Sting Pathway in Metastatic Skin Tumor

Purpose@#Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer. @*Materials and Methods@#The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell. @*Results@#We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA. @*Conclusion@#The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.

Low-grade Rectal Neuroendocrine Tumor Recurring as Multiple Hepatic Metastasis after Complete Endoscopic Removal: A Case Report / 대한소화기학회지

The World Health Organization classified rectal neuroendocrine tumors (NETs) as malignant in 2010 owing to their distant metastasis potential. On the other hand, in cases of small rectal NETs (<10 mm), which have a low risk of metastasis, endoscopic removal is the first-line therapeutic option, and regular surveillance is not recommended. The authors report a case of a small, well-differentiated rectal NET, which recurred as multiple hepatic metastases 5 years after apparent complete removal using endoscopic methods.

Acute Type A Aortic Dissection in a Patient with Situs Inversus Totalis

We describe the occurrence of acute type A aortic dissection in a patient with situs inversus totalis. A 37-year-old man presented to the emergency department with acute chest pain. Initial chest X-ray findings showed a right-sided heart and a left-sided liver. Contrast-enhanced computed tomography revealed a Stanford type A acute aortic dissection, aortic root dilatation, and situs inversus totalis. All of the thoracic structures were mirror-image reversed and an abnormal coronary artery was observed. The Bentall operation was performed. This report demonstrates that computed tomography and echocardiography were useful for understanding the anatomy and the presence or absence of concurrent anomalies in a patient with situs inversus totalis. The patient’s postoperative course was uneventful.

Contribution of Container Types on Cosmetics Contamination

No abstract available.

The usefulness of fecal calprotectin in assessing inflammatory bowel disease activity

BACKGROUND/AIMS: Fecal calprotectin (FC) is known to correlate with disease activity and can be used as a predictor for relapse or treatment response in inflammatory bowel disease (IBD). We evaluated the usefulness of FC as a biomarker for disease activity in patients with IBD using both enzyme-linked immunosorbent assay (ELISA) and a quantitative point-of-care test (QPOCT). METHODS: Fecal samples and medical records were collected from consecutive patients with IBD. FC levels were measured by both ELISA and QPOCT and patient medical records were reviewed for clinical, laboratory, and endoscopic data. RESULTS: Ninety-three patients with IBD were enrolled, 55 with ulcerative colitis (UC) and 38 with Crohn's disease (CD). The mean FC-ELISA levels were 906.3 ± 1,484.9 μg/g in UC and 1,054.1 ± 1,252.5 μg/g in CD. There was a strong correlation between FC-ELISA level and clinical activity indices (p < 0.05). FC-ELISA level was significantly lower in patients with mucosal healing (MH) compared to those without MH in UC (85.5 ± 55.6 μg/g vs. 1,503.7 ± 2,129.9 μg/g, p = 0.005). The results from the QPOCT corresponded well to those from ELISA. A cutoff value of 201.3 μg/g for FC-ELISA and 150.5 μg/g for FC-QPOCT predicted endoscopic inflammation (Mayo endoscopic subscore ≥ 1) in UC with a sensitivity of 81.8% and 85.8%, respectively, and a specificity of 100% for both. CONCLUSIONS: FC was strongly associated with disease activity indices, serologic markers, and endoscopic activity in patients with IBD. QPOCT can be used more conveniently than ELISA to assess FC in clinical practice.

Dental Treatment in a Patient with CINCA Syndrome under General Anesthesia / 대한소아치과학회지

Chronic infantile neurological cutaneous articular (CINCA) syndrome periodically causes fever along with inflammation in multiple organs. Patients with this condition are vulnerable to dental problems due to systemic inflammation. For uncooperative patients, general anesthesia has been widely used to control negative behavior. However, caution should be exercised when administering general anesthesia in these patients because this syndrome is pro-inflammatory. The present case report describes the clinical considerations of the dental treatment of an uncooperative child with CINCA syndrome who was treated under general anesthesia.

Is Clostridium difficile infection a real threat in patients with ulcerative colitis? A prospective, multicenter study in Korea

BACKGROUND/AIMS: Clostridium difficile infection (CDI) has been reported to be a cause of flare-ups in patients with ulcerative colitis (UC). We evaluated the prevalence and clinical outcomes of CDI in patients with UC hospitalized for flare-ups. METHODS: This was a prospective, multicenter study including 7 academic teaching hospitals in Korea. All consecutive patients with UC admitted for disease flare-up were enrolled. We detected the presence of CDI by using enzyme immunoassay, real-time polymerase chain reaction (RT-PCR) for toxin genes, and sigmoidoscopy. RESULTS: Eighty-one consecutive patients with UC were enrolled from January 2014 to December 2015. Among 81 patients, 8 (9.9%) were diagnosed with CDI. Most of the cases were identified by RT-PCR. Enzyme immunoassay was positive in 3 of 8 patients, and only 1 had typical endoscopic findings of pseudomembranous colitis. There were no differences in demographic data, length of hospital stay, or colectomy rate between patients with and without CDI. CONCLUSIONS: CDI was not a rare cause of flare-up in patients with UC in Korea. However, CDI did not appear to affect the course of UC flare-up in Korean patients. RT-PCR was sensitive in detecting CDI and can be considered a diagnostic tool in patients with UC flare-up.

Morin Prevents Granule Cell Dispersion and Neurotoxicity via Suppression of mTORC1 in a Kainic Acid-induced Seizure Model

An abnormal reorganization of the dentate gyrus and neurotoxic events are important phenotypes in the hippocampus of patients with temporal lobe epilepsy (TLE). The effects of morin, a bioflavonoid constituent of many herbs and fruits, on epileptic seizures have not yet been elucidated, though its beneficial effects, such as its anti-inflammatory and neuroprotective properties, are well-described in various neurodegenerative diseases. In the present study, we investigated whether treatment with morin hydrate (MH) can reduce the susceptibility to seizures, granule cell dispersion (GCD), mammalian target of rapamycin complex 1 (mTORC1) activity, and the increases in the levels of apoptotic molecules and inflammatory cytokines in the kainic acid (KA)-induced seizure mouse model. Our results showed that oral administration of MH could reduce susceptibility to seizures and lead to the inhibition of GCD and mTORC1 activity in the KA-treated hippocampus. Moreover, treatment with MH significantly reduced the increased levels of apoptotic signaling molecules and pro-inflammatory mediators in the KA-treated hippocampus compared with control mice, suggesting a neuroprotective role. Therefore, these results suggest that morin has a therapeutic potential against epilepsy through its abilities to inhibit GCD and neurotoxic events in the in vivo hippocampus.

Efficacy of Peracetic Acid (EndoPA®) for Disinfection of Endoscopes / 대한소화기학회지

BACKGROUND/AIMS: We aimed to investigate the efficacy of peracetic acid (EndoPA®; Firson Co., Ltd., Cheonan, Korea) in disinfecting endoscopes. METHODS: We prospectively investigated the gastroscopes (Part I) utilized in 100 gastroscopic examinations and colonoscopes (Part II) utilized in 30 colonoscopic examinations after disinfecting them with 0.2% peracetic acid (EndoPA®; Firson Co., Ltd.). These instruments had been collected consecutively throughout the study period. We reprocessed and disinfected the endoscopes according to the guidelines for cleaning and disinfecting gastrointestinal endoscopes laid down by the Korean Society of Gastrointestinal Endoscopy in 2017. Three culture samples were obtained from each examination, based on different sampling methods. The primary outcome was a positive culture rate. RESULTS: In Part I of our study, two of 300 samples were positive. The culture positive rate after disinfection was 0.7% (2/300). The culture positive rate was not significantly different based on the exposure time to EndoPA® or the age of the scopes (p=0.7 or 0.2, respectively). In Part II of our study, all samples (n=90) were negative. CONCLUSIONS: We conclude that 0.2% peracetic acid (EndoPA®) appears to be a good disinfectant for both gastroscopes and colonoscopes.

Lateral Cephalometric Measurements of Class I Malocclusion Patients with Uncertainty / 대한소아치과학회지

The aim of this study was to obtain the traceability of the software used to analyze lateral cephalometry and to calculate the uncertainty of the measurements. Furthermore, this study aimed to provide a basis for obtaining standard references for measurement values for orthodontic treatment in children.Cephalometric data were collected from 100 children diagnosed with class I malocclusion between the ages 6 to 13 years who visited the pediatric dentist at Seoul National University Dental Hospital. To ensure traceability, a phantom device was created. Correction values were calculated by measuring the length and angle of the phantom device using the software. Type A uncertainty was calculated by obtaining the standard deviation of cephalometric measurements of 100 persons and the standard error of repeated measurements. Determination of the type B uncertainty was induced by minimum resolution and the position of the head. Using these, the combined standard uncertainty was obtained and the expanded uncertainty was calculated.The results of this study confirm that the currently used software has high accuracy and reliability. Furthermore, the uncertainty of orthodontic measurements in Korean children aged 6 to 13 years was calculated, and distribution range for class I malocclusion with 95% confidence interval was suggested.

Hepatocyte toll-like receptor 4 mediates lipopolysaccharide-induced hepcidin expression

Hepcidin expression is induced by inflammatory molecules such as lipopolysaccharide (LPS) via a macrophage-mediated pathway. Although hepatocytes directly respond to LPS, the molecular mechanism underlying toll-like receptor (TLR)-dependent hepcidin expression by hepatocytes is mostly unknown. Here we show that LPS can directly induce the mRNA expression and secretion of hepcidin by hepatocytes via TLR4 activation. Using hepatocytes deficient in TLR4, myeloid differentiation factor 88 (MyD88) and TIR domain-containing adaptor inducing interferon-β (TRIF), we demonstrated that LPS-induced hepcidin expression by hepatocytes is regulated by its specific receptor, TLR4, via a MyD88-dependent signaling pathway. Hepcidin promoter activity was significantly increased by MyD88-dependent downstream signaling molecules (interleukin-1 receptor-associated kinase (IRAK) and tumor necrosis factor receptor-associated factor 6 (TRAF6), which activate c-Jun N-terminal kinase (JNK) and activator protein-1 (AP-1). We then confirmed that LPS stimulation induced the phosphorylation of JNK and c-Jun, and observed strong occupancy of the hepcidin promoter by c-Jun. Promoter mutation analysis also identified the AP-1-binding site on the hepcidin promoter. Finally, bone marrow transplantation between wild-type and TLR4 knockout mice revealed that hepatic TLR4-dependent hepcidin expression was comparable to macrophage TLR4-dependent hepcidin expression induced by LPS. Taken together, these results suggest that TLR4 expressed by hepatocytes regulates hepcidin expression via the IRAK–TRAF6–JNK–AP-1 axis.

Effect of Anti-vascular Endothelial Growth Factor Antibody on the Survival of Cultured Retinal Ganglion Cells

PURPOSE: To investigate the effects of anti-vascular endothelial growth factor (VEGF) antibody on the survival of retinal ganglion cell (RGC)-5 cells differentiated with staurosporine under oxidative stress. METHODS: We used real-time polymerase chain reaction and Western blot to confirm the expression of VEGF, VEGF receptor (VEGFR)-1 and VEGFR-2 in RGC-5 cells differentiated with staurosporine for 6 hours. The differentiated RGC-5 cells were treated with 800 µM hydrogen peroxide (H₂O₂) for 24 hours to induce oxidative stress. Then, the survival rate of RGC-5 was confirmed by lactate dehydrogenase assay at each concentration (0, 0.01, 0.1, and 1 mg) using bevacizumab as the anti-VEGF antibody. The expression of VEGF, VEGFR-1, and VEGFR-2 was confirmed using real-time polymerase chain reaction. RESULTS: VEGF, VEGFR-1, and VEGFR-2 were all expressed in differentiated RGC-5 cells. When RGC-5 cells were simultaneously treated with bevacizumab and 800 µM H₂O₂, survival of RGC-5 decreased with bevacizumab concentration. VEGF expression in RGC-5 cells increased with increasing concentration of bevacizumab. Similar patterns were observed for VEGFR-1 and VEGFR-2, but the degree of increase was smaller than that for VEGF. CONCLUSIONS: When bevacizumab was administered to differentiated RGC-5 cells, the cell damage caused by oxidative stress increased. Therefore, given these in vitro study results, caution should be exercised with bevacizumab treatment.