Novel Histone Deacetylase 6 Inhibitor Confers Anti-inflammatory Effects and Enhances Gut Barrier Function

Background/Aims@#The purpose of the current study was to examine the anti-inflammatory effects of CKD-506, a novel histone deacetylase 6 inhibitor, on human peripheral blood mononuclear cells (PBMCs) and CD4+ T cells and to explore the relationship between CKD-506 and gut epithelial barrier function. @*Methods@#Lipopolysaccharide-stimulated human PBMCs from inflammatory bowel disease (IBD) patients were treated with CKD-506, and tumor necrosis factor (TNF)-α expression was measured using an enzyme-linked immunosorbent assay. The proliferation of CD4+ T cells from IBD patients was evaluated using flow cytometric analysis. The effects of CKD-506 on gut barrier function in a cell line and colon organoids, based on examinations of mRNA production, goblet cell differentiation, and E-cadherin recovery, were investigated using quantitative reverse transcription polymerase chain reaction, immunofluorescence, and a fluorescein isothiocyanatedextran permeability assay. @*Results@#Secretion of TNF-α, a pivotal pro-inflammatory mediator in IBD, by lipopolysaccharidetriggered PBMCs was markedly decreased by CKD-506 treatment in a dose-dependent manner and to a greater extent than by tofacitinib or tubastatin A treatment. E-cadherin mRNA expression and goblet cell differentiation increased significantly and dose-dependently in HT-29 cells in response to CKD-506, and inhibition of E-cadherin loss after TNF-α stimulation was significantly reduced both in HT-29 cells and gut organoids. Caco-2 cells treated with CKD-506 showed a significant reduction in barrier permeability in a dose-dependent manner. @*Conclusions@#The present study demonstrated that CKD-506 has anti-inflammatory effects on PBMCs and CD4 T cells and improves gut barrier function, suggesting its potential as a smallmolecule therapeutic option for IBD.

Downregulation of Heat Shock Protein 72 Contributes to Fibrostenosis in Crohn’s Disease

Background/Aims@#Crohn’s disease (CD) with recurrent inflammation can cause intestinal fibrostenosis due to dysregulated deposition of extracellular matrix. However, little is known about the pathogenesis of fibrostenosis. Here, we performed a differential proteomic analysis between normal, inflamed, and fibrostenotic specimens of patients with CD and investigated the roles of the candidate proteins in myofibroblast activation and fibrosis. @*Methods@#We performed two-dimensional difference gel electrophoresis and identified candidate proteins using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and orbitrap liquid chromatography-mass spectrometry. We also verified the levels of candidate proteins in clinical specimens and examined their effects on 18Co myofibroblasts and Caco-2 intestinal epithelial cells. @*Results@#We identified five of 30 proteins (HSP72, HSPA5, KRT8, PEPCK-M, and FABP6) differentially expressed in fibrostenotic CD. Among these proteins, the knockdown of heat shock protein 72 (HSP72) promoted the activation and wound healing of myofibroblasts. Moreover, knockdown of HSP72 induced the epithelial-mesenchymal transition of intestinal epithelial cells by reducing E-cadherin and inducing fibronectin and α-smooth muscle actin, which contribute tofibrosis. @*Conclusions@#HSP72 is an important mediator that regulates myofibroblasts and epithelial-mesenchymal transition in fibrosis of CD, suggesting that HSP72 can serve as a target for antifibrotic therapy.

Succinate-treated macrophages attenuate dextran sodium sulfate colitis in mice

The safety and effectiveness of adalimumab was demonstrated in a phase 3 trial in Japanese patients with intestinal Behçet’s disease. The aim of this study was to evaluate the long-term safety and effectiveness of adalimumab in Japanese patients with intestinal Behçet’s disease.

Succinate-treated macrophages attenuate dextran sodium sulfate colitis in mice

The safety and effectiveness of adalimumab was demonstrated in a phase 3 trial in Japanese patients with intestinal Behçet’s disease. The aim of this study was to evaluate the long-term safety and effectiveness of adalimumab in Japanese patients with intestinal Behçet’s disease.

Estimates of the Number of Workers Exposed to Diesel Engine Exhaust in South Korea from 1993 to 2013

BACKGROUND: The aim of this study was to estimate the number of workers exposed to diesel engine exhaust (DEE) by industry and year in the Republic of Korea. METHOD: The estimates of workers potentially exposed to DEE in the Republic of Korea were calculated by industry on the basis of the carcinogen exposure (CAREX) surveillance system. The data on the labor force employed in DEE exposure industries were obtained from the Census on Establishments conducted by the Korea National Statistical Office from 1993 to 2013. The mean values of prevalence rates adopted by EU15 countries were used as the primary exposure prevalence rates. We also investigated the exposure prevalence rates and exposure characteristics of DEE in 359 workplaces representing 11 industries. RESULTS: The total number of workers exposed to DEE were estimated as 270,014 in 1993 and 417,034 in 2013 (2.2% of the total labor force). As of 2013, the industry categorized as “Land transport” showed the highest number of workers exposed to DEE with 174,359, followed by “Personal and household services” with 70,298, “Construction” with 45,555, “Wholesale and retail trade and restaurants and hotels” with 44,005, and “Sanitation and similar services” with 12,584. These five industries, with more than 10,000 workers exposed to DEE, accounted for 83% of the total DEE-exposed workers. Comparing primary prevalence rates used for preliminary estimation among 49 industries, “Metal ore mining” had the highest rate at 52.6%, followed by “Other mining” with 50.0%, and “Land transport” with 23.6%. CONCLUSION: The DEE prevalence rates we surveyed (1.3–19.8%) were higher than the primary prevalence rates. The most common emission sources of DEE were diesel engine vehicles such as forklifts, trucks, and vans. Our estimated numbers of workers exposed to DEE can be used to identify industries with workers requiring protection from potential exposure to DEE in the Republic of Korea.

Usefulness of Measuring Serum Procalcitonin Levels in Patients with Inflammatory Bowel Disease

BACKGROUND/AIMS: The relationships between serum procalcitonin, inflammatory bowel disease (IBD) and intestinal Behçet's disease (BD) have not been completely determined. We aimed to evaluate the usefulness of measuring serum procalcitonin levels to assess disease activity and infection stage in patients with IBD and intestinal BD. METHODS: We retrospectively analyzed clinical data from 129 patients with IBD and intestinal BD for whom serum procalcitonin and C-reactive protein (CRP) levels were measured between January 2006 and February 2013. RESULTS: The median serum procalcitonin levels in the IBD and intestinal BD with septic shock or sepsis (n=8), with localized infection (n=76), and without infection (n=45) were 3.46 ng/mL (range, 0.17 to 63.66 ng/mL), 0.22 ng/mL (range, 0.05 to 140.18 ng/mL), and 0.07 ng/mL (range, 0.00 to 31.50 ng/mL), respectively (p=0.001). The serum CRP levels in the IBD and intestinal BD patients did not differ according to the infection stage. Variations in serum procalcitonin levels were not observed in the IBD and intestinal BD patients with different disease activities. CONCLUSIONS: Serum procalcitonin levels may not be affected by IBD and intestinal BD activity itself, although they may be affected by concomitant infection. Serum procalcitonin measurements could be more useful than CRP in determining the infection stage that reflects the severity of infection in IBD and intestinal BD patients.

Correlation between Soluble Triggering Receptor Expressed on Myeloid Cells-1 and Endoscopic Activity in Intestinal Behcet's Disease

PURPOSE: The serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) have recently been shown to be correlated highly with disease activity in patients with intestinal Behcet's disease (BD). However, it remains unclear whether sTREM-1 levels reflect endoscopic activity in intestinal BD. This study aimed to evaluate the correlation of sTREM-1 levels with endoscopic activity in intestinal BD. MATERIALS AND METHODS: A total of 84 patients with intestinal BD were enrolled. Endoscopic activity was compared with sTREM-1 levels as well as other laboratory findings, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). RESULTS: sTREM-1 levels were significantly increased in intestinal BD patients compared with controls (37.98+/-27.09 pg/mL vs. 16.65+/-7.76 pg/mL, p=0.002), however, there was no difference between endoscopically quiescent and active diseases (43.53+/-24.95 pg/mL vs. 42.22+/-32.68 pg/mL, p=0.819). Moreover, serum sTREM-1 levels did not differ in terms of number, shape, depth, size, margin, or type of ulcer in patients with intestinal BD. However, mean ESR and CRP levels in patients with active disease were significantly higher than those in patients with quiescent disease (p=0.001, p<0.001, respectively). In addition, endoscopic activity scores for intestinal BD were correlated significantly with both CRP levels (gamma=0.329) and ESR (gamma=0.298), but not with sTREM-1 levels (gamma=0.166). CONCLUSION: Unlike CRP levels and ESR, serum sTREM-1 levels were not correlated with endoscopic activity in patients with intestinal BD.

Multidimensional Comparison of Personality Characteristics in Genetic High Risk for Schizophrenia, First Episode Psychosis and Healthy Controls / 대한정신분열병학회지

OBJECTIVES: Previous studies have suggested that some personality characteristics are associated with the onset, prognosis and social function in schizophrenia patients. However few is known about the personality and affective characteristic of genetic high risk group (GHR) for schizophrenia. This study aimed to investigate the personality and the affective characteristic of GHR group for schizophrenia. METHODS: Participants were 54 healthy controls (HC), 26 subjects with GHR for schizophrenia and 28 subjects with first episode psychosis (FEP). We performed three self-report questionnaires; NEO-Personality Inventory-Revised, State and Anger Expression Inventory and Positive Affect and Negative Affect Schedule. RESULTS: The GHR group showed higher score in agreeableness item than the HC (p=0.028). In extraversion item, the FEP group showed significantly lower scores than the HC (p=0.001). The GHR group showed lower scores in neuroticism item compared with FEP group in trend level. The FEP group showed higher trait-anger, lower positive affect and higher negative affect compared with the others. CONCLUSION: The GHR group seem to share certain vulnerable personality and affective characteristics for schizophrenia with the FEP group. On the other hands, the GHR group appeared to be more agreeable than the other groups, which might act as the compensation for other impaired functions.

A Case of Iatrogenic Subcutaneous Cervicofacial and Mediastinal Emphysema after Catheterization / 대한이비인후과학회지

Subcutaneous cervicofacial and mediastinal emphysema (SCFME) occur with a variety of disease processes. Most cases involve a passive escape of air from the aerodigestive tract into subcutaneous tissues. Even if the presence of SCFME is not in itself dangerous, prompt recognition of the underlying etiology is essential. Catheterization is a common procedure in the otolaryngologic field, but, clinically, SCFME after catheterization is very rare. Recently, we experienced a case of SCFME after catheterization, so we report this rare case with a review of literatures.

A Case of Nasopharyngeal Tuberculosis with Retropharyngeal Abscess / 대한이비인후과학회지

The nasopharyngeal tuberculosis with retropharyngeal abscess is a rare disease. Recently, the authors experienced a 26 year-old female patient who had been admitted with odynophagia for 1 month. The physical examination revealed isolated granulomatous lesion on the nasopharynx and protrusion of the posterior pharyngeal wall between the nasopharynx and the oropharynx. Biopsies from the nasopharynx showed caseating epitheloid granuloma with multinucleated giant cell. Needle aspiration of the retropharyngeal space yielded 50ml of pus. She was diagnosed with nasopharyngeal tuberculosis with retropharyngeal abscess. We effectively treated her with trial anti-tuberculosis chemotherapy and intraoral drainage. We report it with a review of the literature.

A Study on Worker Exposure to Methylene Chloride in Aircraft Paint Stripping Operation

BACKGROUND: Workers who are related with paint stripping process of aircraft parts can be exposed methylene chloride, phenol, chromium hexavalent in using paint remover. Especially, methylene chloride is more important hazard because of chemical asphyxia. METHOD: NIOSH(National Institute of Occupational Safety and Health) Manual of Analytical Methods(NMAM) #1005 was used in sampling and analysis of methylene chloride. 4 air bases were surveyed. RESULT: Airborne concentrations of methylene chloride distributed lognomally. In aircraft paint stripping operation of 4 air bases, geometric mean(GM) of methylene chloride concentrations was 30.40+/-3.39 ppm (n=14) in personal samples and GM of area samples was 2.24 ppm (n=2). 5 of 8 samples showed breakthrough phenomenon. Breakthrough rate([back section]/[front section]) significantly correlated with airborne concentrations (p<0.01) and with detected amounts of methylene chloride(p<0.01). CONCLUSION: Airborne concentrations of methylene chloride in paint stripping process exceed the criteria level in many case(43%). Seriesed charcoal tubes must be used in methylene chloride sampling in compliance with NMAM.

Expression of Nitiric Oxide Synthase lsoenzymes in Normal Nasal and Polyp Mucosa of Human / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) seems to have some potential to play a regulatory role in the airway function and it maybe related to the pathophysiology of several airway diseases. Although the pathophysiology of nasal polyp is poorly understood, a recent study has suggested that airway NO produced from paranasal sinus epithelium where mNOS is expressed constituitively without immunologic stimulation may play a critical role in the genesis of inflammatory nasal disease. MATERIALS AND METHODS: We examined the presence of mNOS and eNOS in the nasal cavity and paranasal sinus mucosa in 10 healthy persons of nasal septal deviation and 20 patients with nasal polyp by immunohistochemical staining using rabbit polyclonal anti- eNOS and anti-mNOS IgG. Relative quantification of eNOS and mNOS was done by RT-PCR. RESULTS: Immunoreactivity to eNOS and mNOS was positive in all nasal polyps and this reactivity was mainly restricted to the epithelial layer. Immunoreactivity to mNOS in the controls was negative for the inferior turbinate. RT-PCR showed more mNOS reactivity in the nasal polyp than in the control (p<0.03). CONCLUSION: These findings reinforce the concept that the epithelial layer is the main locus and mNOS may be one of the potential factors in the pathogenesis of nasal polyp.

A Study on the Effects of Taking the Drink Containing Benzoic Acid on Analysis of Hippuric Acid in Urine

BACKGROUND: Benzoic acid contained in some food can hinder the biological monitoring of hippuric acid in urine, which is frequently used as an exposure index of toluene and xylene. METHOD: 20 male examinees who are not exposed to organic solvents in their jobs were given a bottle of drink containing benzoic acid(70 mg/dl) and took it. Urine samples were taken from every person just before, in 1.5 hrs after, and in 3 hrs after taking the drink. Hippuric acid in urine was analyzed with improved Ogata and Taguchi method and creatinine with Jaffe method. RESULT: Mean hippuric acid concentrations in urine just before, in 1.5 hrs after, and in 3 hrs after taking the drink were 0.59+/-0.21 g/g creatinine, 2.75+/-0.98 g/g creatinine, 1.04+/-0.58 g/g creatinine, respectively. And, each group had statistically significant differences (p<0.01). There were no statistically significant differences between two groups categorized by age, smoking, and drinking. CONCLUSION: From the results, we suggest that when hippuric acid concentration in urine is used as a exposure index of toluene, it should be surveyed whether the food containing benzoic acid was taken or not.

Clinical Study in Nocturnal Enuretic Children

PURPOSE: Nocturnal Enuresis, an involuntary discharge of urine after bladder control, is frequent in children. It brings patients and family many psychogenic problems. So we investigated its clinical characteristics and drug effects. METHODS: The study subjects enrolled were 36 children with nocturnal enuresis. We evaluated family history, accompanying urinary symptoms and clinical characteristics through questionnaries. We evaluated the effect of imipramine and desmopressin in 26 children among the 36 cases. RESULTS: The ratio of boys to girls was 1.6 to 1. The age range in 15 cases(41.7%) was 4-5 years, in 14 cases(38.9%) 6-7 years, in 4 cases(11.1%) 8-9 years, and in 3 cases(9.3%) it was above 10 years. Twenty four(67%) were primary enuresis and 12(33%) were secondary enuresis. In eighteen cases(50%), these was a family history of enuresis. Seven of these cases had a parental enuresis history. The accompanying urinary symptoms were urgency(47.2%), frequency (38.9%), and dysuria(13.9%). The responses to imipramine were as follows : an excellent response in 2 cases(20%), a good response in 4(40%), a transient response in 2(20%), and no response in 2(20%). The responses to desmopressin were as follows : an excellent response in 7(43.8%), a good response in 4(25%), a transient response in 3(18.7%), and no response in 2(12.5%). CONCLUSION: Enuresis is more frequent in boys and primary type. Half of 36 enuresis children had a family history of enuresis. We recommend continuous drug medication to control nocturnal enuresis along with encouragement.

Clinical Study in Nocturnal Enuretic Children

PURPOSE: Nocturnal Enuresis, an involuntary discharge of urine after bladder control, is frequent in children. It brings patients and family many psychogenic problems. So we investigated its clinical characteristics and drug effects. METHODS: The study subjects enrolled were 36 children with nocturnal enuresis. We evaluated family history, accompanying urinary symptoms and clinical characteristics through questionnaries. We evaluated the effect of imipramine and desmopressin in 26 children among the 36 cases. RESULTS: The ratio of boys to girls was 1.6 to 1. The age range in 15 cases(41.7%) was 4-5 years, in 14 cases(38.9%) 6-7 years, in 4 cases(11.1%) 8-9 years, and in 3 cases(9.3%) it was above 10 years. Twenty four(67%) were primary enuresis and 12(33%) were secondary enuresis. In eighteen cases(50%), these was a family history of enuresis. Seven of these cases had a parental enuresis history. The accompanying urinary symptoms were urgency(47.2%), frequency (38.9%), and dysuria(13.9%). The responses to imipramine were as follows : an excellent response in 2 cases(20%), a good response in 4(40%), a transient response in 2(20%), and no response in 2(20%). The responses to desmopressin were as follows : an excellent response in 7(43.8%), a good response in 4(25%), a transient response in 3(18.7%), and no response in 2(12.5%). CONCLUSION: Enuresis is more frequent in boys and primary type. Half of 36 enuresis children had a family history of enuresis. We recommend continuous drug medication to control nocturnal enuresis along with encouragement.

The mechanism of c-erbB-2 gene product increase in stomach cancer cell lines

c-erbB-2 oncogene encodes a growth factor receptor whose amino acid sequence has extensive homology with human epidermal growth factor receptor. It is frequently overexpressed in human breast, ovary, lung, and stomach cancers, where its overexpression is related significantly to the prognosis. Tl investigate the possible role of c-erbB-2 oncogene in the oncogenesis of stomach cancer, we examined the genetic alterations of c-erbB-2 oncogene in 4 stomach cancer cell lines, SNU-1, SNU-5, SNU-16 and KATO III. There were no differences in c-erbB-2 mRNA level as well as c-erbB-2 gene copy number among them. But gp185-erbB-2, c-erbB-2 gene product, was increased from 2- to 4-fold in SNU-1 and SNU-5 cells, compared with that in SNU-16 or KATO III cells. Our results suggest that post-transcriptional regulation of gp185erbB-2 expression may underlie gp185erbB-2 overexpression in cancer cells.

Observation of the Serum Uric Acid in Essential Hypertension

We studied serum uric acid in 120 patients of essential hypertension visiting Department of Internal Medicine of Seoul Red Cross Hospital from October 1985 to November 1986 and analyzed its values in terms of various clinical and laboratory parameters. The results wereas follows; 1) The mean concentration of serum uric acid and incidence of hyperuricemia were 6.5+/-1.86mg%, 50.8% in hypertension group and those of normal control were 3.75+/-1.27mg%, 13.3%, respectively with significant high values in hypertension group. 2) The mean concentration of serum uric acid and the incidence of hyperuricemia were significantly correlated with the levels of diastolic blood pressure but there was only correlation between the incidence of hyperuricemia and the level of systolic pressure. 3) The mean concentration of serum uric acid and the incidence of hyperuricemia were significantly correlated with the level of BUN and serum creatinine, especially more in serum creatinine. 4) The mean concentration of serum uric acid and the incidence of hyperuricemia were not correlated with each level of serum cholesterol and triglyceride. 5) There was significant correlation between mean concentration of serum uric acid and abnormal urine finding but not in incidence of hyperuricemea.