BMD42-2910, a Novel Benzoxazole Derivative, Shows a Potent Anti-prion Activity and Prolongs the Mean Survival in an Animal Model of Prion Disease

Prion diseases are a group of neurodegenerative and fatal central nervous system disorders. The pathogenic mechanism involves the conversion of cellular prion protein (PrPC) to an altered scrapie isoform (PrPSc), which accumulates in amyloid deposits in the brain. However, no therapeutic drugs have demonstrated efficacy in clinical trials. We previously reported that BMD42-29, a synthetic compound discovered in silico , is a novel anti-prion compound that inhibits the conversion of PrPC to protease K (PK)-resistant PrPSc fragments (PrPres). In the present study, 14 derivatives of BMD42-29 were obtained from BMD42-29 by modifying in the side chain by in silico feedback, with the aim to determine whether they improve anti-prion activity. These derivatives were assessed in a PrPSc-infected cell model and some derivatives were further tested using real timequaking induced conversion (RT-QuIC). Among them, BMD42-2910 showed high anti-prion activity at low concentrations in vitro and also no toxic effects in a mouse model. Interestingly, abundant PrPres was reduced in brains of mice infected with prion strain when treated with BMD42- 2910, and the mice survived longer than control mice and even that treated with BMD42-29. Finally, high binding affinity was predicted in the virtual binding sites (Asn159, Gln 160, Lys194, and Glu196) when PrPC was combined with BMD-42-2910. Our findings showed that BMD42-2910 sufficiently reduces PrPres generation in vitro and in vivo and may be a promising novel anti-prion compound.

Indoor pet ownership in infancy is a risk factor for the development of sensitization to pets and asthma in childhood

PURPOSE: It is controversial whether indoor pet exposure is either a risk or protective factor developing sensitization to pet allergens or asthma. Therefore, we investigated whether indoor pet ownership entails a risk for the development of asthma and sensitization in childhood. METHODS: The Panel Study of Korean Children (PSKC) is a general-population-based birth cohort study that recruited 2,078 mother-baby dyads in Korea between April and July of 2008. Among 1,577 children who were followed up in 2015, 559 underwent skin prick tests, spirometry and bronchial provocation tests using Provocholine. Having a cat or a dog and the prevalence of asthma were evaluated by using self-reported questionnaires and physicians’ medical records. RESULTS: During infancy, the rate of dog ownership was 4.5% (71 of 1,574) and that of cat ownership was 0.5% (8 of 1,574). Of the subjects, 7.9% (n=109) currently had at least 1 dog and 2.5% (n=34) had at least 1 cat. Pet ownership during infancy was associated with sensitization to cats or dogs (adjusted odds ratio [aOR], 4.24; 95% confidence interval [CI], 1.29–13.98), wheezing within 12 months (aOR, 5.56; 95% CI, 1.65–18.75) and current asthma (wheezing episode in the last 12 months+diagnosed asthma by physicians) (aOR, 6.36; 95% CI, 1.54–26.28). In contrast, pet ownership during the last 12 months was not associated with sensitization to cats or dogs or current asthma. CONCLUSION: Indoor pet exposure during infancy can be critical for developing sensitization to cats or dogs and asthma in childhood. Avoidance of pet exposure in early life may reduce sensitization to cats or dogs and development of asthma.

Outcomes of drug provocation tests in Korean children with suspected drug hypersensitivity reaction

PURPOSE: Drug provocation tests (DPT) are the gold standard for confirming the diagnosis of drug hypersensitivity reactions (DHRs). However, there are little studies of DPT in children. The purpose of this study was to evaluate DPT results and safety as diagnostic methods of DHR in Korean children. METHODS: We reviewed the medical records of 39 children under 18 years of age with a suspected DHR and performed DPT between January 2010 and May 2016 at Asan Medical Center. RESULTS: Total 110 DPT were performed in 39 children (20 boys and 19 girls) with a history of DHR. Clinical presentation of DHR included skin rash (n=7), pruritus (n=3), urticaria (n=18), angioedema (n=19), dyspnea (n=5), hoarseness (n=1), hypothermia (n=1), and anaphylaxis (n=5). The median age at the time of DPT was 9 years. Positive DPT were observed in 21 of 39 children (53.8%) and 28 of 110 cases (25.5%). Drugs causing positive reactions were acetaminophen in 50% (9 of 18), nonsteroidal anti-inflammatory drugs in 29.2% (14 of 48), cephalosporin in 9.1% (1 of 11), trimethoprim/sulfamethoxazole in 50% (1 of 2), local anesthetics in 10% (1 of 10), and others (levodropropizine and idursulfase) in 15.4% (2 of 13). There was no statistical difference between children who had positive and negative results in sex, age, personal and parental history of allergic disease, eosinophil count, or total IgE level. Children with positive DPT did not develop anaphylaxis during the DPT procedure. CONCLUSION: Drug provocation test is safe, and it can be considered in children with suspected DHRs.

The First Successful Lung Transplantation in a Korean Child with Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive inherited multisystem disorder caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Respiratory failure remains the most frequent cause of morbidity and mortality. Lung transplantation is the only option to treat end-stage lung disease. Very few cases of CF occur in Koreans. We report the case of a 12-year-old girl with respiratory failure due to CF who underwent lung transplantation. She had been diagnosed with CF 8 years previously after being treated for recurrent Pseudomonas aeruginosa pneumonia and malnutrition based on sweat chloride concentrations and the CFTR protein gene mutation test. Progression to end-stage lung disease and respiratory failure led to registration with the Korean Network for Organ Sharing. She underwent successful double lung transplantation in 2014. Although she has diabetes mellitus and chronic kidney disease, she has a better quality of life and a prolonged life expectancy.

Inhibitory Effect of Metformin Therapy on the Incidence of Colorectal Advanced Adenomas in Patients With Diabetes

BACKGROUND/AIMS: Metformin use has been associated with decreased colorectal cancer risk and mortality among diabetic patients. Recent research suggests that metformin use may decrease the incidence of colorectal adenomas in diabetic patients with previous colorectal cancer. This study aimed to assess the clinical effect of metformin use on the development of colorectal adenomas in diabetic patients without previous colorectal cancer. METHODS: Among 604 consecutive diabetic patients who underwent colonoscopic surveillance after initial colonoscopy between January 2002 and June 2012, 240 patients without previous colorectal cancer were enrolled in this study and were divided in two groups: 151 patients receiving metformin and 89 patients not receiving metformin. Patient demographics and clinical characteristics as well as the colorectal adenoma incidence rate were retrospectively analyzed. RESULTS: The incidence rate of total colorectal adenomas was not different according to metformin use (P=0.349). However, the advanced adenoma incidence rate was significantly lower in the metformin group compared with the non-metformin group (relative risk [RR], 0.09; P=0.011). Metformin use was independently associated with a decreased incidence of advanced colorectal adenomas after adjustment for clinically relevant factors (RR, 0.072; P=0.016). In addition, the cumulative development rate of advanced adenomas during follow-up was significantly lower in the metformin group compared with the non-metformin group (P=0.007). CONCLUSIONS: Metformin use in diabetic patients without previous colorectal cancer is associated with a lower risk of advanced colorectal adenomas.

Inhibitory Effect of Metformin Therapy on the Incidence of Colorectal Advanced Adenomas in Patients With Diabetes

BACKGROUND/AIMS: Metformin use has been associated with decreased colorectal cancer risk and mortality among diabetic patients. Recent research suggests that metformin use may decrease the incidence of colorectal adenomas in diabetic patients with previous colorectal cancer. This study aimed to assess the clinical effect of metformin use on the development of colorectal adenomas in diabetic patients without previous colorectal cancer. METHODS: Among 604 consecutive diabetic patients who underwent colonoscopic surveillance after initial colonoscopy between January 2002 and June 2012, 240 patients without previous colorectal cancer were enrolled in this study and were divided in two groups: 151 patients receiving metformin and 89 patients not receiving metformin. Patient demographics and clinical characteristics as well as the colorectal adenoma incidence rate were retrospectively analyzed. RESULTS: The incidence rate of total colorectal adenomas was not different according to metformin use (P=0.349). However, the advanced adenoma incidence rate was significantly lower in the metformin group compared with the non-metformin group (relative risk [RR], 0.09; P=0.011). Metformin use was independently associated with a decreased incidence of advanced colorectal adenomas after adjustment for clinically relevant factors (RR, 0.072; P=0.016). In addition, the cumulative development rate of advanced adenomas during follow-up was significantly lower in the metformin group compared with the non-metformin group (P=0.007). CONCLUSIONS: Metformin use in diabetic patients without previous colorectal cancer is associated with a lower risk of advanced colorectal adenomas.

Hazard Classification of Household Chemical Products in Korea according to the Globally Harmonized System of Classification and labeling of Chemicals

OBJECTIVES: This study was conducted to review the validity of the need for the application of the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) to household chemical products in Korea. The study also aimed to assess the severity of health and environmental hazards of household chemical products using the GHS. METHODS: 135 products were classified as 'cleaning agents and polishing agents' and 98 products were classified as 'bleaches, disinfectants, and germicides.' The current status of carcinogenic classification of GHS and carcinogenicity was examined for 272 chemical substances contained in household chemical products by selecting the top 11 products for each of the product categories. In addition, the degree of toxicity was assessed through analysis of whether the standard of the Republic of Korea's regulations on household chemical products had been exceeded or not. RESULTS: According to GHS health and environmental hazards, "acute toxicity (oral)" was found to be the highest for two product groups, 'cleaning agents and polishing agents', and 'bleaches, disinfectants, and germicides' (result of classification of 233 household chemical products) at 37.8% and 52.0% respectively. In an analysis of carcinogenicity assuming a threshold of IARC 2B for the substances in household chemical products, we found 'cleaning agents and polishing agents' to contain 12 chemical substances and 'bleaches, disinfectants, and germicides' 11 chemical substances. CONCLUSION: Some of the household chemical products were found to have a high hazard level including acute toxicity and germ cell mutagenicity, carcinogenicity, and reproductive toxicity. Establishing a hazard information delivery system including the application of GHS to household chemical products in Korea is urgent as well.

Desalinated underground seawater of Jeju Island (Korea) improves lipid metabolism in mice fed diets containing high fat and increases antioxidant potential in t-BHP treated HepG2 cells

This study was performed to investigate the effect of desalinated underground seawater (named as 'magma seawater', MSW) of Jeju Island in Korea on lipid metabolism and antioxidant activity. MSW was collected from underground of Han-Dong in Jeju Island, and freely given to high fat diet (HFD)-fed C57BL/6 mice for 10 weeks. Although there were no significant differences in the body weight changes and plasma lipid levels, hepatic triglyceride levels were significantly lower in the MSW group than in the normal tap water (TW)-drunken control group. Furthermore, the activity of fatty acid synthase (FAS) was significantly decreased and carnitine palmitoyltransferase (CPT) activity was increased in MSW group compared to TW group. Similarly, real-time PCR analysis revealed that mRNA expressions of lipogenic genes were lowered in MSW groups compared to the control group. In a morphometric observation on the liver tissue, accumulation of fats was remarkably reduced in MSW group. Meanwhile, in vitro assay, free radical scavenging activity measured by using diphenylpicrylhydrazyl (DPPH) was increased in MSW group. The 2'-7'-dichlorofluorescein diacetate (DCF-DA) staining followed with fluorescent microscopy showed a low intensity of fluorescence in MSW-treated HepG2 cells, compared to TW-treated HepG2 cells, which indicated that the production of reactive oxygen species by tert-butyl hydroperoxide (t-BHP) in HepG2 cells was decreased by MSW treatment. The antioxidant effect of MSW on t-BHP-induced oxidative stress in HepG2 cells was supported by the increased activities of intracellular antioxidant enzymes such as catalase and glutathione reductase. From these results, we speculate that MSW has an inhibitory effect on lipogenesis in liver and might play a protective role against cell damage by t-BHP-induced oxidative stress.

Diagnosis and management of primary malignant melanoma of the lung: a case report / 대한내과학회지

Melanoma develops in the skin or the mucosa of organs. It spreads via lymphatic channels or the bloodstream to the regional lymph nodes or organs such as the brain, liver, and lung. Melanoma of the lung is nearly always metastatic, and primary malignant melanoma of the lung is very rare, with only 30 cases reported in the English literature. The possibility of skin lesions that have disappeared, or of undetected primary sites, makes it difficult to confirm true primary tumors. Therefore, a thorough workup is needed to make the diagnosis. Since metastatic melanoma is incurable, the goal of treatment is palliation. However, because of the rare experience of primary melanoma of the lung, it is difficult to predict the prognosis. We experienced one patient with primary malignant melanoma of the lung with metastases who had been managed with surgery, interferon-alpha, chemotherapy, and radiation therapy over 5 years. This case report presents the diagnosis and management of primary malignant melanoma of the lung.

Phlebosclerotic Colitis in a Cirrhotic Patient with Portal Hypertension: The First Case in Korea

Phlebosclerotic colitis is a rare form of ischemic colitis characterized by the thickening of the wall of the affected colon due to fibrous degeneration of submucosal layer of colon and fibrotic obstruction of the colono-mesenteric vein, resulting in the disturbance of venous return from the colon. The pathogenic mechanism of this entity remains unknown but chronic liver disease with portal hypertension is maybe thought to be one of the speculated mechanisms. Here we first report the case of surgically confirmed phlebosclerotic colitis, that was in the early stage but showed the aggressive nature, in a 61-yr-old cirrhotic patients with portal hypertension in Korea.

A Case of Hemocholecyst / 대한소화기학회지

No abstract available.

A Case of Wernicke's Encephalopathy Occurring in a Patient with Aspiration Pneumonia: A Case Report / 대한구급학회지

Wernicke's encephalopathy is a neurologic complication of thiamine deficiency, presenting with acute confusion, oculomotor dysfunction, and gait ataxia. While most often associated with chronic alcoholism, Wernicke's encephalopathy occasionally occurs in the setting of poor nutritional status, such as malabsorption, increased metabolic requirements, or increased loss of the water-soluble vitamins. Patients with critical illnesses can present with excessive catabolic status because of activation of the sympathetic nervous system and the pituitary-adrenal axis. In addition, inappropriate nutritional evaluation and lack of concerns for adequate nutrient support can increase the morbidity and mortality in such patients. However, the importance of adequate nutritional support is often disregarded during treatment of the patient's primary illness. We have recently managed a patient with Wernicke's encephalopathy and pneumonia who did not receive adequate nutritional support during hospitalization. We report this case to call attention to the importance of nutritional support in critically ill patients.