Background/Aims: Previous studies have reported the protective effects of tauroursodeoxycholic acid (TUDCA) on gastric epithelial cells in some animal models, but the precise mechanisms are unclear. This study examined the effects of TUDCA on NF-κB signaling in gastric epithelial cells. Moreover, the protective effects of TUDCA in experimental gastritis models induced by ethanol and NSAID were evaluated and compared with ursodeoxycholic acid (UDCA). Methods: After a pretreatment with TUDCA or UDCA, human gastric epithelial MKN-45 cells were stimulated with tumor necrosis factor (TNF)-α to activate NF-κB signaling. A real-time PCR (RT-PCR) for human interleukin (IL)-1 mRNA was performed. An electrophoretic mobility shift assay (EMSA) and immunoblot analyses were carried out. In murine models, after a pretreatment with TUDCA or UDCA, ethanol and indomethacin were administered via oral gavage. Macroscopic and microscopic assessments were performed to evaluate the preventive effects of TUDCA and UDCA on murine gastritis. Results: A pretreatment with TUDCA downregulated the IL-1α mRNA levels in MKN-45 cells stimulated with TNF-α, as assessed by RT-PCR. As determined using EMSA, a pretreatment with TUDCA reduced the TNF-α-induced NF-κB DNA binding activity. A pretreatment with TUDCA inhibited IκBα phosphorylation induced by TNF-α, as assessed by immunoblot analysis. TUDCA attenuated the ethanol-induced and NSAID-induced gastritis in murine models, as determined macroscopically and microscopically. Conclusions TUDCA inhibited NF-κB signaling in gastric epithelial cells and ameliorated ethanol- and NSAID-induced gastritis in murine models. These results support the potential of TUDCA for the prevention of gastritis in humans.

Background: The fatality rate of patients with coronavirus disease 2019 (COVID-19) varies among countries owing to demographics, patient comorbidities, surge capacity of healthcare systems, and the quality of medical care. We assessed the clinical outcomes of patients with COVID-19 during the first wave of the epidemic in Korea. Methods: Using a modified World Health Organization clinical record form, we obtained clinical data for 3,060 patients with COVID-19 treated at 55 hospitals in Korea. Disease severity scores were defined as: 1) no limitation of daily activities; 2) limitation of daily activities but no need for supplemental oxygen; 3) supplemental oxygen via nasal cannula; 4) supplemental oxygen via facial mask; 5) non-invasive mechanical ventilation; 6) invasive mechanical ventilation; 7) multi-organ failure or extracorporeal membrane oxygenation therapy; and 8) death. Recovery was defined as a severity score of 1 or 2, or discharge and release from isolation. Results: The median age of the patients was 43 years of age; 43.6% were male. The median time from illness onset to admission was 5 days. Of the patients with a disease severity score of 3–4 on admission, 65 (71.5%) of the 91 patients recovered, and 7 (7.7%) died due to illness by day 28. Of the patients with disease severity scores of 5–7, 7 (19.5%) of the 36 patients recovered, and 8 (22.2%) died due to illness by day 28. None of the 1,324 patients who were < 50 years of age died; in contrast, the fatality rate due to illness by day 28 was 0.5% (2/375), 0.9% (2/215), 5.8% (6/104), and 14.0% (7/50) for the patients aged 50–59, 60–69, 70–79, and ≥ 80 years of age, respectively. Conclusion In Korea, almost all patients of < 50 years of age with COVID-19 recovered without supplemental oxygen. In patients of ≥ 50 years of age, the fatality rate increased with age, reaching 14% in patients of ≥ 80 years of age.

PURPOSE: To evaluate changes in the peripapillary retinal nerve fiber layer (RNFL) thicknesses using spectral-domain optical coherence tomography (SD-OCT) in hydroxychloroquine (HCQ) users. METHODS: The medical records of HCQ users were retrospectively reviewed. In these HCQ users, an automated perimetry, fundus autofluorescence photography, and SD-OCT with peripapillary RNFL thickness measurements were performed. The peripapillary RNFL thicknesses were compared between the HCQ users and the control groups. The relationships between the RNFL thicknesses and the duration or cumulative dosage of HCQ use were analyzed. RESULTS: This study included 77 HCQ users and 20 normal controls. The mean duration of HCQ usage was 63.6 ± 38.4 months, and the cumulative dose of HCQ was 528.1 ± 3.44 g. Six patients developed HCQ retinopathy. Global and six sectoral RNFL thicknesses of the HCQ users did not significantly decrease compared to those of the normal controls. No significant correlation was found between the RNFL thickness and the duration of use or cumulative dose. The eyes of those with HCQ retinopathy had temporal peripapillary RNFL thicknesses significantly greater than that of normal controls. CONCLUSIONS: The peripapillary RNFL thicknesses did not change in the HCQ users and did not correlate with the duration of HCQ use or cumulative doses of HCQ. RNFL thickness is not a useful biomarker for the early detection of HCQ retinal toxicity.
Humans ; Hydroxychloroquine* ; Medical Records ; Nerve Fibers* ; Photography ; Retinaldehyde* ; Retrospective Studies ; Tomography, Optical Coherence ; Visual Field Tests

This study aimed to evaluate the frequency and clinical characteristics of hydroxychloroquine (HCQ) retinopathy in Korean patients with rheumatologic diseases. We retrospectively reviewed medical records of 310 patients taking HCQ. Ophthalmic examinations included spectral-domain optical coherence tomography (SD-OCT), automated visual field test, and fundus autofluorescence. The severity of retinopathy was categorized as early, moderate, or severe, and the location was categorized as parafoveal, pericentral, or mixed pattern. Among 310 patients, 9 patients (2.9%) were diagnosed as HCQ retinopathy. Among the patients with HCQ use ≥ 5 years (n = 174), the frequency was 5.2%. Only 1 (11.1%) of the 9 patients was symptomatic. The mean daily dose per kilogram of real body weight of the 9 patients was 5.6 mg, and only 3 had used 6.5 mg or more. Four of the 9 patients had severe HCQ retinopathy. Six of the 9 patients showed pericentral or mixed pattern of retinal damage. Consequently, the frequency of HCQ retinopathy in Korean patients was not low, especially when administered at a high cumulative dose and for a long duration. Screening of HCQ retinopathy by the recommended guidelines that include SD-OCT seems useful and should be done to detect retinal damage earlier in patients with chronic exposure to HCQ.
Body Weight ; Humans ; Hydroxychloroquine* ; Mass Screening ; Medical Records ; Retinaldehyde ; Retrospective Studies ; Tomography, Optical Coherence ; Visual Field Tests

The posaconazole tablet formulation was developed to have improved bioavailability compared to the oral suspension. Here, we compared posaconazole plasma concentration (PPC) with the posaconazole oral suspension versus the tablet in Korean patients undergoing remission induction chemotherapy for hematologic malignancies. PPC was measured at 3, 8, and 15 days of treatment with the oral suspension (174 patients) or the tablet (40 patients). At all time-points, mean PPC was significantly higher with the tablet compared to the oral suspension. Our findings suggest that posaconazole tablets generate an optimal PPC earlier and in more patients than the oral suspension among Korean patients.
Antifungal Agents ; Biological Availability ; Dosage Forms ; Drug Therapy ; Hematologic Neoplasms* ; Humans ; Plasma* ; Remission Induction ; Tablets

BACKGROUND/AIMS: Interstitial cells of Cajal (ICC) play important functions in motor activity of the gastrointestinal tract. The role of ICC as pacemakers is well established, however their participation in neurotransmission is controversial. Studies using mutant animals that lack ICC have yielded variable conclusions on their importance in enteric motor responses. The purpose of this study was to: (1) clarify the role of intramuscular ICC (ICC-IM) in gastric motor-neurotransmission and (2) evaluate remodeling of enteric motor responses in W/W(V) mice. METHODS: Kit immunohistochemistry and post-junctional contractile responses were performed on fundus muscles from wild-type and W/W(V) mice and quantitative polymerase chain reaction (qPCR) was used to evaluate differences in muscarinic and neurokinin receptor expression. RESULTS: Although ICC-IM were greatly reduced in comparison with wild-type mice, we found that ICC-IM persisted in the fundus of many W/W(V) animals. ICC-IM were not observed in W/W(V) group 1 (46%) but were observed in W/W(V) group 2 (40%). Evoked neural responses consisted of excitatory and inhibitory components. The inhibitory component (nitrergic) was absent in W/W(V) group 1 and reduced in W/W(V) group 2. Enhanced excitatory responses (cholinergic) were observed in both W/W(V) groups and qPCR revealed that muscarinic-M3 receptor expression was significantly augmented in the W/W(V) fundus compared to wild-type controls. CONCLUSIONS: This study demonstrates that ICC-IM mediate nitrergic inhibitory neurotransmission in the fundus and provides evidence of plasticity changes in neuronal responses that may explain discrepancies in previous functional studies which utilized mutant animals to examine the role of ICC-IM in gastric enteric motor responses.
Animals ; Enteric Nervous System ; Gastric Fundus* ; Gastrointestinal Tract ; Immunohistochemistry ; Interstitial Cells of Cajal* ; Mice* ; Motor Activity ; Motor Neurons* ; Muscle Relaxation ; Muscle, Smooth ; Muscles ; Neurons ; Plastics ; Polymerase Chain Reaction ; Synaptic Transmission

The gastrointestinal motility is regulated by extrinsic and intrinsic neural regulation. Intrinsic neural pathways are controlled by sensory input, inter-neuronal relay and motor output. Enteric motor neurons release many transmitters which affect post-junctional responses. Post-junctional responses can be excitatory and inhibitory depending on neurotransmitters. Excitatory neurotransmitters induce depolarization and contraction. In contrast, inhibitory neurotransmitters hyperpolarize and relaxe the gastrointestinal smooth muscle. Smooth muscle syncytium is composed of smooth muscle cells, interstitial cells of Cajal and platelet-derived growth factor receptor alpha-positive (PDGFRalpha+) cells (SIP syncytium). Specific expression of receptors and ion channels in these cells can be affected by neurotransmitters. In recent years, molecular reporter expression techniques are able to study the properties of ion channels and receptors in isolated specialized cells. In this review, we will discuss the mechanisms of ion channels to interpret the post-junctional responses in the gastrointestinal smooth muscles.
Gastrointestinal Motility ; Giant Cells ; Interstitial Cells of Cajal ; Ion Channels ; Motor Neurons ; Muscle, Smooth ; Myocytes, Smooth Muscle ; Neural Pathways ; Neurotransmitter Agents ; Receptors, Platelet-Derived Growth Factor

BACKGROUND: Data on the clinicopathologic features of hair follicle tumors in Korea are limited. OBJECTIVE: The purpose was to investigate the clinical and histopathologic characteristics of hair follicle tumors in Korea. METHODS: Two hundred sixty four cases of hair follicle tumors seen from 1999 to 2001 in Korea were analyzed clinically and histopathologically. RESULTS AND CONCLUSION: The most common hair follicle tumor in Korea was pilomatricoma(81.0%), followed by trichoepithelioma(6.4%), dilated pore of Winer(3.8%), and proliferating trichilemmal tumor(2.2%). Hair follicle tumors usually occurred as a solitary skin-colored nodule. The most commonly involved site was the face, and the peak age of presentation was 10 to 19. Pilomatricoma usually occurred as a solitary skin-colored nodule. The most commonly involved site was the arm, and more than 50% of tumors occurred before the age of 20. Histopathologically, the tumor was often surrounded by fibrous capsule and was composed of basophilic and shadow cells. It was usually located in the dermis and extended into the subcutis. Retraction spaces between tumor nests and stroma were frequently observed. Trichoepithelioma usually occurred as multiple skin-colored papules on the face. Histopathologically, the tumor was usually located in the dermis with sometimes connected to the epidermis. It frequently showed peripheral palisading. Dilated pore of Winer usually occurred as a solitary brownish to pigmented papule on the face in middle-aged persons. Proliferating trichilemmal tumor occurred as a solitary or multiple tumors. Histopathologically, the tumor was usually surrounded by incomplete fibrous capsule. Tumor cells frequently showed clear cell formation, nuclear atypia, mitosis, peripheral palisading, trichilemmal keratinization, and individual keratinization.
Arm ; Basophils ; Dermis ; Epidermis ; Hair Follicle* ; Hair* ; Humans ; Korea ; Mitosis ; Pilomatrixoma

The prevalence of Behcet's disease is the highest in the East Asian and the Medi-terranean countries. Behcet's disease is also distributed in the Asian countries, but the nationwide survey has not been performed in Korea yet. The Korean Study Group for Behcet's Disease, founded in 1999, conducted a multicenter, retrospective survey on epidemiologic and clinical features of the patients with Behcet's disease from 20 hospitals around the nation from 1997 to 1999. Of 3,497 patients, 1,527 were classified into complete or incomplete type of Behcet's disease according to the revised Shimizu's classification. The sex ratio was 1:1.75 with the female predominance. Geographical distribution showed the highest frequency in Seoul (38.5%). Clinically, 98.8% had oral ulcers, 83.2% had genital ulcers, 84.3% had skin lesions and 50.9% had ocular lesions. As for the minor clinical manifestations, articular symptoms were the most frequent. The pathergy test showed positive in 15.4% of patients and revealed a higher positive rate in males (20.2%) than in females (12.7%). In conclusion, we performed the first multicenter study on Behcet's disease in Korea and revealed the female predominance, higher frequency of ocular lesions, and lower positivity of pathergy test in the patients.
Adolescence ; Adult ; Aged ; Behcet's Syndrome/complications/*epidemiology ; Child ; Child, Preschool ; Female ; Human ; Infant ; Korea/epidemiology ; Male ; Middle Age ; Prevalence ; Retrospective Studies ; Sex Distribution

Peritonitis remains the leading cause of the patient dropout in CAPD in many developing countries. In Korea, 71% of CAPD patients dropout is caused by peritonitis. To elucidate an adequate guideline for treating peritonitis in our country, we analyzed clinical and bacteriologic profiles of peritonitis(1995. 1. 1- 1999. 12. 31). Two hundred and twenty eight episodes of peritonitis were developed in 127/247 patients. The incidence of peritonitis was 0.41/patient-year in general, which was decreased to 0.24/patient-year in 1999. The incidence of causative organisms were as follows; 82(36.0%) by Gram positive organisms, 38 (16.2%) by gram negative organisms, 16 cases(7.0%) by mixed organsisms, and 5 cases(2.2%) by fungus. During study period, the incidence of peritonitis by gram positive organsism was decreased while the incidence of peritonitis by gram negative organism was not changed. Recurrent infection/relapse was noted in 58 patients(45%). Peritonitis were eradicated only in 66% of the cases by initial antibiotics(cefazolin+aminoglycoside); and another 17% responded by second line antibiotics. Peritoneal catheters were removed in 38 episodes(16.7%). Patients with exit infection were more frequent in removal of catheter. Risk factor analysis was performed in 146 patients, who were newly started CAPD. There were 60 initial episodes of peritonitis(mean duration of follow up was 16.7 patient months). Sixty-five percent were free of peritonitis at the end of first year, 54% at the end of second year and 45% at the end of third year (Kaplan-Meier). Factors such as age, sex, underlying DM, were not risk factor for CAPD peritonitis. In conclusion, we observed that the incidence of peritonitis decreased every year. It was revealed however that only 66% of peritonitis can be successfully treated by first line antibiotics. Second line antibiotics such as ceftazidime may need to be introduced in early phase of CAPD peritonitis. Up to one third of patients had recurrent infection/relapse, which raised the incidence of peritonitis. Continuing education as well as better exit care is needed to improve technical survival of CAPD patients in Korea.
Anti-Bacterial Agents ; Catheters ; Ceftazidime ; Developing Countries ; Education, Continuing ; Follow-Up Studies ; Fungi ; Humans ; Incidence ; Korea ; Patient Dropouts ; Peritoneal Dialysis, Continuous Ambulatory* ; Peritonitis* ; Risk Factors*