SARS‑CoV‑2 Omicron variant causes brain infection with lymphoid depletion in a mouse COVID‑19 model / 한국실험동물학회지

Background@#The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. @*Results@#K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. @*Conclusion@#Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

The effects of curcumin on the fibrous envelope surrounding silicone implants in rats

Background@#Capsular contracture is the most common serious breast surgery complication. The cause of capsular formation remains unknown, but chronic inflammation is commonly considered to cause excessive fibrosis. Curcumin has anti-inflammatory effects and thus can relieve the symptoms of inflammatory diseases, as demonstrated in animal studies. This study aimed to evaluate the effects of curcumin on the fibrous envelope covering silicone implants in a rat model. @*Methods@#Two solid 1.8-cm oval-shaped silicone implants were placed beneath both sides of the back in 20 Sprague-Dawley rats. The control group included 10 rats that were fed a normal diet (group A), while the experimental group (group B) included the remaining 10 rats that were fed ground curcumin. En bloc excision was conducted at 8 postoperative weeks. Capsular thickness and inflammatory cell distribution were examined using a fixed tissue sample. @*Results@#Gross findings and histologic differences between the groups were observed. The experimental group had a significantly lower mean total capsular thickness than the control group (177.4±31.4 μm vs. 145.9±32.5 μm, P=0.007). A significant decreasing tendency was found in several inflammatory cells in the experimental group (7,070±744.3/mm2 vs. 2,640±301.7/mm2, P=0.001). @*Conclusions@#Curcumin significantly reduced the inflammatory reaction, and will help to lower the risk of capsular contracture. Long-term studies are required to determine whether this hypothesis can provide a basis for a viable therapeutic strategy to reduce capsular contracture.

Establishment of particulate matterinduced lung injury model in mouse / 한국실험동물학회지

Background@#Particulate matter (PM) is one of the principal causes of human respiratory disabilities resulting from air pollution. Animal models have been applied to discover preventive and therapeutic drugs for lung diseases caused by PM. However, the induced severity of lung injury in animal models using PM varies from study to study due to disparities in the preparation of PM, and the route and number of PM administrations. In this study, we established an in vivo model to evaluate PM-induced lung injury in mice. @*Results@#PM dispersion was prepared using SRM2975. Reactive oxygen species were increased in MLE 12 cells exposed to this PM dispersion. In vivo studies were conducted in the PM single challenge model, PM multiple challenge model, and PM challenge with ovalbumin-induced asthma using the PM dispersion. No histopathological changes were observed in lung tissues after a single injection of PM, whereas mild to moderate lung inflammation was obtained in the lungs of mice exposed to PM three times. However, fibrotic changes were barely seen, even though transmission electron microscopy (TEM) studies revealed the presence of PM particles in the alveolar macrophages and alveolar capillaries. In the OVA-PM model, peribronchial inflammation and mucous hypersecretion were more severe in the OVA+PM group than the OVA group. Serum IgE levels tended to increase in OVA+PM group than in OVA group. @*Conclusions@#In this study, we established a PM-induced lung injury model to examine the lung damage induced by PM. Based on our results, repeated exposures of PM are necessary to induce lung inflammation by PM alone. PM challenge, in the presence of underlying diseases such as asthma, can also be an appropriate model for studying the health effect of PM.

Establishment of particulate matterinduced lung injury model in mouse / 한국실험동물학회지

Background@#Particulate matter (PM) is one of the principal causes of human respiratory disabilities resulting from air pollution. Animal models have been applied to discover preventive and therapeutic drugs for lung diseases caused by PM. However, the induced severity of lung injury in animal models using PM varies from study to study due to disparities in the preparation of PM, and the route and number of PM administrations. In this study, we established an in vivo model to evaluate PM-induced lung injury in mice. @*Results@#PM dispersion was prepared using SRM2975. Reactive oxygen species were increased in MLE 12 cells exposed to this PM dispersion. In vivo studies were conducted in the PM single challenge model, PM multiple challenge model, and PM challenge with ovalbumin-induced asthma using the PM dispersion. No histopathological changes were observed in lung tissues after a single injection of PM, whereas mild to moderate lung inflammation was obtained in the lungs of mice exposed to PM three times. However, fibrotic changes were barely seen, even though transmission electron microscopy (TEM) studies revealed the presence of PM particles in the alveolar macrophages and alveolar capillaries. In the OVA-PM model, peribronchial inflammation and mucous hypersecretion were more severe in the OVA+PM group than the OVA group. Serum IgE levels tended to increase in OVA+PM group than in OVA group. @*Conclusions@#In this study, we established a PM-induced lung injury model to examine the lung damage induced by PM. Based on our results, repeated exposures of PM are necessary to induce lung inflammation by PM alone. PM challenge, in the presence of underlying diseases such as asthma, can also be an appropriate model for studying the health effect of PM.

Inhibition of STAT3 signaling induces apoptosis and suppresses growth of lung cancer: good and bad / 한국실험동물학회지

Signal transducer and activator of transcription 3 (STAT3) modulates a variety of genes involved in the regulation of critical functions, including cell proliferation, differentiation, apoptosis, angiogenesis, metastasis, and immunity. For many cancers, elevated levels of STAT3 signaling have been associated with a poor prognosis and the development of chemotherapy resistance. In this study, we investigated the inhibitory effects of a novel small-molecule inhibitor of STAT3, STX-0119, on the cell viability and survival of human lung cancer cells. STX-0119 inhibited activated STAT3 and the expression of STAT3-regulated oncoproteins such as c-Myc, cyclin D1, and survivin in lung cancer cells. STX-0119 also decreased the amount of STAT3 in the nuclear fraction as well as induced apoptosis of these lung cancer cell lines as evidenced by increases in apoptotic cells (Annexin V positive) and poly (ADP-ribose) polymerase (PARP) cleavage. The efficacy of STX-0119 in a mouse xenograft model was confirmed. However, a hematological side effect, which had not been previously reported, was observed. The level of white blood cells was significantly lowered when treated at the dose at which STX-0119 alone showed a significant tumor-suppressive effect. In conclusion, we suggest that STX-0119 may be a potent therapeutic agent against lung cancer. Consideration of the side effect suggests, it is necessary to study whether low-dose STX-0119 is effective for lung treatment with a combination of classic lung cancer therapeutics.

Gastrointestinal Stromal Tumor of the Stomach Presenting as a Perigastric Abscess

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. A 77-year-old man was referred for the evaluation of general weakness and leukocytosis. Computed tomography showed a 9.5×6.5-cm cavitary lesion with an air-fluid level near the stomach, which was thought to be a perigastric abscess. Upper endoscopy revealed a fistula on the greater curvature at the mid body of the stomach. The margin of the fistula opening was clearly demarcated, and yellow turbid fluid oozing from the fistula was seen. Laparoscopic wedge resection was performed at the perforated area of the stomach. Immunohistochemistry revealed CD117 expression. A diagnosis of intermediate-risk GIST was made. No recurrence was identified within 18 months after the operation. The final diagnosis was perforated gastric GIST communicating with the gastric lumen and presenting as an intra-abdominal abscess.

A Case of a Rapidly Progressive Small Bowel Lymphoma with High Ki-67 Expression

Primary intestinal lymphoma is a rare disease. It accounts for approximately 1~4% of gastrointestinal malignancy. Extranodal lymphoma of the intestine mainly arises from B cells. Diffuse large B-cell lymphoma is the most common type of the disease. Approximately 40% of intestinal lymphoma can be cured, while 60% have varied disease progression. Ki-67 proliferation has been recently used as an index of cell growth to predict the progression of the disease. Reported herein is a case of a rapidly progressive small bowel diffuse large B-cell lymphoma in a 51-year-old man with a high Ki-67 expression level. He visited the emergency department because of hematochezia. Abdominal computed tomography revealed distal small bowel segmental wall thickening. He underwent operation due to spontaneous small bowel perforation. The result of the pathological examination of the resected specimen was compatible with diffuse large B-cell lymphoma. The Ki-67 index within 5 months was 90%.

Helicobacter pylori Eradication Rate in Patients with Diabetes

BACKGROUND/AIMS: The prevalence of diabetes mellitus is increasing. Little is known about the difference in Helicobacter pylori eradication rates between diabetic patients and non-diabetics. The aim of this study was to compare the eradication rate between diabetic and non-diabetic patients. MATERIALS AND METHODS: The medical records of patients who received a proton pump inhibitor (PPI)-based eradication therapy between 2012 and 2015 were retrospectively reviewed. All the patients underwent endoscopic biopsy to confirm H. pylori infection. Successful eradication was confirmed by using the ¹³C-urea breath test, biopsy, or rapid urease test, which was performed at least 4 weeks after the end of eradication therapy. RESULTS: A total of 1,402 patients were included. The eradication rate was 74.3% (1,041/1,402; 95% CI, 72.0~76.5%). Excluding 151 patients who were confirmed to have no diabetes, 182 diabetic and 1,069 non-diabetic patients were compared. No significant difference (P=0.667) in eradication rate with PPI-amoxicillin-clarithromycin therapy was found between the diabetic (75.8%, 138/182; 95% CI, 69.6~82.0%) and non-diabetic groups (74.0%, 791/1,069; 95% CI, 71.4~76.6%). Peptic ulcer was much more common in the diabetic group than in the non-diabetic group (67.0% vs. 57.9%, P=0.038). CONCLUSIONS: The H. pylori eradication rate with PPI-based triple therapy in the diabetic patients was probably not different from that in non-diabetic patients.

Fermented Pueraria Lobata extract ameliorates dextran sulfate sodium-induced colitis by reducing pro-inflammatory cytokines and recovering intestinal barrier function / 한국실험동물학회지

Inflammatory bowel disease is a chronic inflammatory disorder occurring in the gastrointestinal track. However, the efficacy of current therapeutic strategies has been limited and accompanied by side effects. In order to eliminate the limitations, herbal medicines have recently been developed for treatment of IBD. Peuraria Lobata (Peuraria L.) is one of the traditional herbal medicines that have anti-inflammatory effects. Bioavailability of Peuraria L., which is rich in isoflavones, is lower than that of their fermented forms. In this study, we generated fermented Peuraria L. extracts (fPue) and investigated the role of fPue in inflammation and intestinal barrier function in vitro and in vivo. As the mice or intestinal epithelial cells were treated with DSS/fPue, mRNA expression of pro-inflammatory cytokines was reduced and the architecture and expression of tight junction proteins were recovered, compared to the DSS-treated group. In summary, fPue treatment resulted in amelioration of DSS-induced inflammation in the colon, and the disrupted intestinal barrier was recovered as the expression and architecture of tight junction proteins were retrieved. These results suggest that use of fPue could be a new therapeutic strategy for treatment of IBD.

A Case of Ulcerative Colitis Following Acute Hepatitis Induced by Epstein-Barr Virus Infection / 대한소화기학회지

Epstein-Barr virus (EBV) infection varies in its clinical manifestations and severity. EBV can be a causative agent of hepatitis and may have a role in the pathogenesis of chronic autoimmune diseases including inflammatory bowel disease. A 24-year-old woman was admitted to our hospital, presenting with fever and elevated liver enzymes. She was diagnosed with acute hepatitis and EBV infection according to serologic tests and liver biopsy. Within two months, she was re-admitted to our hospital, presenting with hematochezia and lower abdominal pain. She was diagnosed with ulcerative colitis. In situ hybridization for EBV was positive in initial liver biopsy and colon biopsy. Here we report an unusual case of acute EBV hepatitis followed at a short interval by ulcerative colitis.

Helicobacter apodemus sp. nov., a new Helicobacter species identified from the gastrointestinal tract of striped field mice in Korea

A novel Helicobacter species was identified from the gastrointestinal tract of the Korean striped field mouse (Apodemus agrarius). Biochemical testing, ultrastructure characterization, and 16S rRNA gene sequence analysis suggested that this bacterium represents a distinct taxon. The bacterium was positive for urease activity, susceptible to cephalothin and nalidixic acid, and weakly positive for oxidase and catalase activity. Electron microscopy revealed that the bacterium has spirally curved rod morphology with singular bipolar nonsheathed flagella. Genotypically, the isolated bacterial strains (YMRC 000215, YMRC 000216, and YMRC 000419) were most closely related to a reference strain of Helicobacter mesocricetorum (97.25%, 97.32%, and 97.03% 16S rRNA sequence similarities, respectively). The 16S rRNA sequences of these strains were deposited into GenBank under accession numbers AF284754, AY009129, and AY009130, respectively. We propose the name Helicobacter apodemus for this novel species.

Effects of Total Thyroidectomy and Radioactive Iodine Therapy for Thyroid Cancer Patients on Sleep Apnea and Snoring / 신경정신의학

OBJECTIVES: Some paper claim thyroidectomy decreases snoring and sleep apnea symptoms and the opposite. The aim of this study is to evaluate and compare the effects of sleep apnea and snoring by total thyroidectomy and radioactive iodine (RI) therapy. METHODS: A total of 88 patients who underwent total thyroidectomy and RI therapy for thyroid cancer in the outpatient clinic of the department of surgery of a general hospital were recruited. Interviewers completed their demographic data, past medical history, and data on total thyroidectomy and sleep apnea with snoring, and also preoperative and postoperative Pittsburgh Sleep Quality Index (PSQI), preoperative and postoperative Epworth Sleepiness Scale (ESS), preoperative and postoperative Snoring Index (SI), preoperative and postoperative global life satisfaction (index of well-being) scale, and postoperative Beck Depression Inventory. RESULTS: The Wilcoxon Signed Ranks Test showed PSQI preoperative-postoperative p=0.750, ESS preoperative-postoperative p=0.000, SI preoperative-postoperative p=0.034, life satisfaction preoperative-postoperative p=0.216 (based on negative ranks). CONCLUSION: The above results indicate that snoring and daytime sleepiness increased after total thyroidectomy and RI therapy, suggesting that the patency of upper airway (UA) was reduced or the collapsibility of the UA increased after total thyroidectomy and RI therapy. That is, the above results indicate that sleep apnea and snoring were aggravated after total thyroidectomy and RI therapy.

Giant Eccrine Hidradenoma Mimicking a Malignant Tumor of the Salivary Gland

No abstract available.

Analysis of Stromal Vascular Fraction from Lipoaspirates: Our Institute's Experiences

Today, adipose tissue derived mesenchymal stem cells (ADSC) have gained a great interest in various medical fields due to the characteristics of its self-renewal and multilineage differentiation capacity. The stromal vascular fraction (SVF) of adipose tissue is known to contain mesenchymal stem cells and it is obtained by processing the lipoaspirate which is usually collected from tumescent liposuction. In this study, we reviewed the records of patient epidemiology and results of SVF isolation. 30 patients (8 males and 22 females) had been underwent tumescent liposuction between April 2012 and January 2013, and the collected lipoaspirates were processed to isolate SVF in GMP facility in CHA Bundang Medical Center. The average stem cell count per 1 cc of lipoaspirate was 52,252 +/- 26,704 and cell count including red blood cells per 1cc of lipoaspirate was 970,607 +/- 873,436. The stem cell viability was proven to be 84 +/- 4%. Bacteria were not detected in all the SVF samples. Compared to previous reports concerning the yield of SVF, our results coincide well with the results of previous studies. Because there were no domestic report about the yield and viability of SVF, this report may provide a reference value of the Korean SVF for the clinicians who want to use SVF as a therapeutic purpose.

Jejunal Perforation Caused by Primary Jejunal Diffuse Large B Cell Lymphoma

Small bowel malignancy accounts for approximately 2% of gastrointestinal malignancies. In particular, malignant lymphoma of the small intestine is so rare that it accounts for less than 1% of gastrointestinal malignancies. Initial symptoms are non-specific and diagnosis may be delayed until the patient presents with complications such as intestinal obstruction, hemorrhage, or perforation. A 79-year-old man visited the emergency room with lower abdominal pain. Segmental resection of the small intestine was done and surgery revealed a 9.5x6 cm sized mass with jejunal perforation at 20 cm inferior to the ligament of Treitz. The mass was diagnosed as diffuse large B cell lymphoma. We experienced a case of diffuse large B cell lymphoma which was diagnosed after emergent surgery for jejunal perforation, and report it with a review of literature.

A Large Hematoma Due to Benign Ulcer Perforation of the Gastric Fundus Resembling Submucosal Tumor / 대한소화기내시경학회지

The gastric fundus is a rare site for benign ulcer and perforation to occur. A 47 year-old male presented to the emergency department with epigastric pain. An endoscopic examination revealed a submucosal tumor-like lesion with friable, superficial ulceration in the high body of the stomach. We performed surgical resection to rule out malignancy because of the lesion's large size and we found chronic gastric ulcer perforation, which was pathologically diagnosed. We presumed that the formation of the large hematoma, which mimicked a submucosal tumor, was a result of repeated bleeding, perforation and healing. We report here on a case of a large hematoma due to a benign gastric ulcer perforation in the fundus, and this all mimicked a submucosal tumor.

Assessment of experimental saccular aneurysm using selective angiography in common carotid artery of rabbits / 대한해부학회지

In order to study the treatment of aneurysms, the technique of making experimental aneurysms in laboratory animals must be established. In our study, to examine the feasibility of making experimental aneurysm and selective angiography on the common carotid artery in rabbits and to determine the size of experimental aneurysm after surgery, saccular aneurysms were fashioned on the right common carotid artery in 17 rabbits using a vein pouch technique. Selective angiography of the common carotid artery was performed immediately after surgery, and at 1 week, 4 weeks, and 8 weeks after surgery. Also, histological changes in the aneurysms were observed. In 16 rabbits with established successful experimental aneurysm, no differences were found in diet intake and behavior before and after surgery. The patency of the carotid artery was confirmed by selective angiography. The average size of the aneurysm immediately after surgery was similar to that of 1 week postoperatively in selective angiography, however it increased with time at 4weeks and 8 weeks. Histologically, infiltration of inflammatory cells and hemorrhage were found at the junction of the carotid artery and the vein pouch at 1 week, which disappeared at 4 weeks and 8 weeks. This study suggests experimental saccular aneurysm using the vein pouch technique might form aneurysms similar to that of the human in its properties such as increment of size, and selective angiography might be suitable for assessment of experimental aneurysm. Therefore, this animal model may be suitable for investigating new treatment methodologies for human aneurysms.

A Case of Retrograde Jejunogastric Intussusception Diagnosed by Gastroscopy / 대한소화기내시경학회지

Retrograde intussusception of the jejunum into the stomach through the stroma of a gastroenterostomy is a very rare, but potentially fatal complication after gastrectomy. Once symptoms develop, the mortality rate is high if this is not treated within 48 hours, so making an early diagnosis with a high index of suspicion and administering prompt treatment are mandatory. Gastroscopy could be a useful diagnostic tool for patients with a history of gastrectomy and who present with abdominal pain and hematemesis, and with considering the possibility of intussusception. A 65-year-old man with a history of Billroth II gastrectomy that was done 35 years ago due to gastric ulcer perforation was admitted with abdominal pain and hematemesis. A necrotic mucosa that was suspicious of an intussuscepted small bowel tissue was detected on gastroscopy. Subsequent open reduction and small bowel resection was performed with successful results. We report here on a case of postoperative retrograde jejunogastric intussusception that occurred 35 years after Billroth II gastrectomy, and it was first diagnosed by performing gastroscopy.

A Case of Gitelman's Like Syndrome Presenting with Rhabdomyolysis / 대한신장학회잡지

Gitelman syndrome is an autosomal recessive hereditary disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, salt wasting, low blood pressure, and hypocalciuria. Gitelman's syndrome is generally considered to be benign, and muscle weakness may be the only manifestation of hypokalemia. To our knowledge, there have been no case reports of rhabdomyolysis due to severe hypokalemia of Gitelman's syndrome in Korea. We report a case of Gitelman's like syndrome presenting with paralysis of both lower extrimities and myalgia. Rhabdomyolysis caused by severe hypokalemia was diagnosed and recovered with supportive therapy, including the administration of 0.9% normal saline and KCl.

Proteomic analysis of the cellular proteins induced by adaptive concentrations of hydrogen peroxide in human U937 cells

When cells are first exposed to low levels of oxidative stress, they develop a resistance to a subsequent challenge of the same stress, even at higher levels. Although some protein(s) induced by oxidative stress likely mediated this adaptive response, the nature of these proteins is unknown. In this study, the total proteins extracted from human U937 leukemia cells exposed to 50 mM H2O2 for 24 h to induce an optimal protective response were analyzed by two-dimensional polyacrylamide gel electrophoresis. H2O2 treatment induced elevation of level of 34 protein spots. An analysis of these spots by a matrix associated laser desorption/ionization time-of-flight mass spectrometry identified 28 of the H2O2-induced proteins. These include proteins involved in energy metabolism, translation and RNA processing, chaperoning or mediating protein folding, cellular signaling, and redox regulation, as well as a mitochondrial channel component, and an actin-bundling protein. Therefore, it appears that the cellular adaptation to oxidative stress is a complex process, and is accompanied by a modulation of diverse cellular functions.