Background/Aims: Recent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes. Methods: We performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases. Results: Abnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID-19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p<0.05). The median time to release from quarantine was longer (22 days vs 26 days, p=0.001) and the mortality rate was higher (13.0% vs 2.9%, p<0.001) in patients with abnormal aminotransferase levels. Conclusions Abnormal aminotransferase levels are common in COVID-19 patients and are associated with poor clinical outcomes. Multivariate analysis of patients with normal aminotransferase levels on admission showed that the use of lopinavir/ritonavir and antibiotics was associated with abnormal aminotransferase levels; thus, careful monitoring is needed.

Background/Aims: Recent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes. Methods: We performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases. Results: Abnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID-19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p<0.05). The median time to release from quarantine was longer (22 days vs 26 days, p=0.001) and the mortality rate was higher (13.0% vs 2.9%, p<0.001) in patients with abnormal aminotransferase levels. Conclusions Abnormal aminotransferase levels are common in COVID-19 patients and are associated with poor clinical outcomes. Multivariate analysis of patients with normal aminotransferase levels on admission showed that the use of lopinavir/ritonavir and antibiotics was associated with abnormal aminotransferase levels; thus, careful monitoring is needed.

Background/Aims: Although coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, the implication of pre-existing liver disease on the outcome of COVID-19 remains unresolved.
Methods: A total of 1,005 patients who were admitted to five tertiary hospitals in South Korea with laboratory-confirmed COVID-19 were included in this study. Clinical outcomes in COVID-19 patients with coexisting liver disease as well as the predictors of disease severity and mortality of COVID-19 were assessed.
Results: Of the 47 patients (4.7%) who had liver-related comorbidities, 14 patients (1.4%) had liver cirrhosis. Liver cirrhosis was more common in COVID-19 patients with severe pneumonia than in those with non-severe pneumonia (4.5% vs. 0.9%, P=0.006). Compared to patients without liver cirrhosis, a higher proportion of patients with liver cirrhosis required oxygen therapy; were admitted to the intensive care unit; had septic shock, acute respiratory distress syndrome, or acute kidney injury; and died (P<0.05). The overall survival rate was significantly lower in patients with liver cirrhosis than in those without liver cirrhosis (log-rank test, P=0.003). Along with old age and diabetes, the presence of liver cirrhosis was found to be an independent predictor of severe disease (odds ratio, 4.52; 95% confidence interval [CI], 1.20–17.02;P=0.026) and death (hazard ratio, 2.86; 95% CI, 1.04–9.30; P=0.042) in COVID-19 patients.
Conclusions This study suggests liver cirrhosis is a significant risk factor for COVID-19. Stronger personal protection and more intensive treatment for COVID-19 are recommended in these patients.

Objective To investigate the composition of volatile compounds in the different accessions of Perilla frutescens (P. frutescens) collected from various habitats of China and Japan. Methods In the present study, the essential oil from the leaves of P. frutescens cultivars from China and Japan was extracted by hydro-distillation and the chemical composition and concentration of the volatile components present in the oils were determined by gas chromatography–mass spectrometry (GC–MS) analysis. Results Among the volatile components, the major proportion was of perilla ketone, which was followed by elemicin and beta-caryophyllene in the Chinese Perilla cultivars. The main component in the oil extracted from the Japanese accessions was myristicin, which was followed by perilla ketone and beta-caryophyllene. We could distinguish seven chemotypes, namely the perilla ketone (PK) type, perilla ketone, myristicin (PM) type, perilla ketone, unknown (PU) type, perilla ketone, beta-caryophyllene, myristicine (PB) type, perilla ketone, myristicin, unknown (PMU) type, perilla ketone, elemicine, myristicin, beta-caryophyllene (PEMB) type, and the perilla ketone, limonene, beta-cryophyllene, myristicin (L) type. Most of the accessions possessed higher essential oil content before the flowering time than at the flowering stage. The average plant height, leaf length, leaf width of the Chinese accessions was higher than those of the Japanese accessions. Conclusion The results revealed that the harvest time and geographical origin caused polymorphisms in the essential oil composition and morphological traits in the Perilla accessions originating from China and Japan. Therefore, these chemotypes with desirable characters might be useful for industrial exploitation and for determining the harvest time.

BACKGROUND/OBJECTIVES: The purpose of the current study was to investigate the effect of red pericarp glutinous rice rich in polyphenols (Jakwangchalbyeo, red rice) on serum and hepatic levels of cholesterol and hepatic protein expression linked to synthesis and degradation of cholesterol in a hypercholesterolemic mice diet as compared with brown rice. MATERIALS/METHODS: C57BL/6 male mice were randomly divided into four groups (n = 5 each), which were fed different diets for a period of 12 weeks: American Institute of Nutrition (AIN)-93G diet, AIN-93G diet with 2% cholesterol, brown rice with 2% cholesterol, or red rice with 2% cholesterol. RESULT: Consumption of red rice resulted in a significant decrease in serum level of low-density lipoprotein cholesterol and hepatic levels of triglyceride and total-cholesterol. Expression of acyl-coenzyme A cholesterol acyltransferase-2 (ACAT-2), sterol regulatory element binding protein-2 (SREBP-2), and 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase was decreased, while expression of phosphorylated adenosine monophosphate activated protein kinase (p-AMPK)/AMPK ratio, cholesterol 7-alpha-hydroxylase (CYP7a1), and sterol 12-alpha-hydroxylase (CYP8b1) was increased in mice fed red rice. Brown rice had similar effects on cholesterol metabolism, but the effect of red rice was significantly greater than that of brown rice. CONCLUSIONS: The current study suggested that red rice had a hypocholesterolemic effect by lowering hepatic cholesterol synthesis through ACAT-2, HMG-CoA reductase, and SREBP-2, and by enhancing hepatic cholesterol degradation through CYP7a1 and CYP8b1 in mice fed a hypercholesterolemic diet.
Adenosine Monophosphate ; Animals ; Cholesterol 7-alpha-Hydroxylase ; Cholesterol* ; Coenzyme A ; Diet* ; Humans ; Lipoproteins ; Liver ; Male ; Metabolism* ; Mice* ; Oxidoreductases ; Phenol* ; Polyphenols ; Protein Kinases ; Steroid 12-alpha-Hydroxylase ; Triglycerides

This study investigated the hypothesis that a sorghum extract exerts anti-diabetic effects through a mechanism that improves insulin sensitivity via peroxisome proliferator-activated receptor gamma (PPAR-gamma) from adipose tissue. Seven C57BL/6 mice were fed an AIN-93M diet with fat consisting of 10% of total energy intake (LF) for 14 weeks, and 21 mice were fed a high-fat AIN diet with 60% of calories derived from fat (HF). From week 8, the HF diet-fed mice were orally administered either saline (HF group), 0.5% (0.5% SE group), or 1% sorghum extract (1% SE group) for 6 weeks (n = 7/group). Perirenal fat content was significantly lower in the 0.5% SE and 1% SE groups than that in the HF mice. Levels of total and low-density lipoprotein cholesterol, triglycerides, glucose, and the area under the curve for glucose were significantly lower in mice administered 0.5% SE and 1% SE than those in HF mice. Serum insulin level was significantly lower in mice administered 1% SE than that in HF mice or those given 0.5% SE. PPAR-gamma expression was significantly higher, whereas the expression of tumor necrosis factor-alpha was significantly lower in mice given 1% SE compared to those in the HF mice. Adiponectin expression was also significantly higher in mice given 0.5% SE and 1% SE than that in the HF mice. These results suggest that the hypoglycemic effect of SE may be related with the regulation of PPAR-gamma-mediated metabolism in this mouse model.
Adiponectin ; Adipose Tissue ; Animals ; Cholesterol ; Diet ; Diet, High-Fat ; Energy Intake ; Glucose ; Hypoglycemic Agents ; Insulin ; Insulin Resistance ; Lipoproteins ; Mice ; PPAR gamma ; Sorghum ; Triglycerides ; Tumor Necrosis Factor-alpha

TNF-alpha is a major cytokine involved in inflammatory bowel disease (IBD). In this study, water extract of Grifola frondosa (GFW) was evaluated for its protective effects against colon inflammation through the modulation of TNF-alpha action. In coculture of HT-29 human colon cancer cells with U937 human monocytic cells, TNF-alpha-induced monocyte adhesion to HT-29 cells was significantly suppressed by GFW (10, 50, 100 microg/ml). The reduced adhesion by GFW correlated with the suppressed expression of MCP-1 and IL-8, the major IBD-associated chemokines. In addition, treatment with GFW significantly suppressed TNF-alpha-induced reactive oxygen species production and NF-kappaB transcriptional activity in HT-29 cells. In differentiated U937 monocytic cells, LPS-induced TNF-alpha production, which is known to be mediated through NF-kappaB activation, was significantly suppressed by GFW. In an in vivo rat model of IBD, oral administration of GFW for 5 days (1 g/kg per day) significantly inhibited the trinitrobenzene sulfonic acid (TNBS)-induced weight loss, colon ulceration, myeloperoxidase activity, and TNF-alpha expression in the colon tissue. Moreover, the effect of GFW was similar to that of intra-peritoneal injection of 5-aminosalicylic acid (5-ASA), an active metabolite of sulfasalazine, commonly used drug for the treatment of IBD. The results suggest that GFW ameliorates colon inflammation by suppressing production of TNF-alpha as well as its signaling through NF-kappaB leading to the expression of inflammatory chemokines, MCP-1 and IL-8. Taken together, the results strongly suggest GFW is a valuable medicinal food for IBD treatment, and thus may be used as an alternative medicine for IBD.
Animals ; Cell Adhesion/drug effects/immunology ; Cell Extracts/administration & dosage/*pharmacology ; Chemokine CCL2/biosynthesis/genetics ; Coculture Techniques ; Colon/drug effects/*metabolism/pathology ; Grifola ; HT29 Cells ; Humans ; Inflammatory Bowel Diseases/chemically induced/*drug therapy/pathology/physiopathology ; Interleukin-8/biosynthesis/genetics ; Intestinal Mucosa/*drug effects/metabolism/pathology ; Monocytes/*drug effects/metabolism/pathology ; NF-kappa B/genetics/metabolism ; Peroxidase/metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Stomach Ulcer ; Transcription, Genetic/drug effects ; Trinitrobenzenesulfonic Acid/administration & dosage ; Tumor Necrosis Factor-alpha/*biosynthesis/genetics ; U937 Cells ; Weight Loss

The observation that ascorbate known to retain pro-oxidant properties induces cell death in a number of immortal cell lines, led us to examine its mechanism and whether it is involved in oxidative stress injury in such asocorbate-enriched tissue cells as hepatocytes. In rat liver homogenates, higher concentrations (1 and 3 mM) of ascorbate suppressed lipid peroxide productions but lower concentrations (0.1 and 0.3 mM) did not. In contrast to the homogenate, ascorbate increased lipid peroxide production in liver slices in a concentration dependant manner. Iso-ascorbate, the epimer of ascorbate did not cause an increase the oxidative stress in liver slices. This differential effect between homogenates and liver slices implies that cellular integrity is required for ascorbate to induce oxidative stress. Wortmannin, an inhibitor of the GLUT (glucose transporter) thought to transport dehydroascorbate into cells, inhibited [14C]- ascorbate uptake and suppressed oxidative stress in liver slices. Wortmannin suppressed that [14C]- ascorbate uptake by GLUT following oxidation to [14C]dehydroascorbate. Taken together, these observations support our hypothesis that ascorbate is oxidized to dehydroascorbate by molecular oxygen in solution (i.e., plasma and culture medium) which is then carried into hepatocytes (via a GLUT) where it is reduced back to ascorbate causing oxidative stress.
Androstadienes/pharmacology ; Animals ; Ascorbic Acid/*metabolism/*pharmacology ; Biological Transport ; Edetic Acid/pharmacology ; Glutathione/*metabolism ; In Vitro ; Liver/*drug effects/*metabolism ; Male ; Oxidation-Reduction/drug effects ; Oxidative Stress/*drug effects ; Rats ; Rats, Sprague-Dawley ; Thiobarbituric Acid Reactive Substances/metabolism ; Time Factors

OBJECTIVES: To investigate the prevalence of cognitive impairment and dementia in elderly people, aged 65 or above, residing in Busan Metropolitan City. METHODS: Total of 1, 101 old people, aged 65 or above, living in Busan as of December 31, 2001 were selected using stratified three-stage cluster sampling. Cognitive impairment was determined from the MMSE-K score, and dementia confirmed from five psychometric measures and the Barthel index. The crude prevalence, sex-age adjusted for the Korean population, were obtained. RESULTS: With the cut-off point for cognitive impairment was set at 24 points, or below, on the MMSE-K scale, the crude rate of cognitive impairment was 29.3% (15.7% for men and 37.5% for women), and the sex-age adjusted prevalence was 30.5% (17.5% for men and 37.0% for women). When the cut-off point for cognitive impairment was set at 20 points, or below, on the MMSE-K scale, the crude rate of cognitive impairments were 10.0% (4.1% for men and 13.5% for women), and 10.6% (4.7% for men and 13.1% for women), respectively. The crude dementia, and the sex-age adjusted rates were 7.4% (2.4% for men and 10.5% for women), and 8.0% (2.7% for men and 10.0% for women), respectively. CONCLUSIONS: The prevalence of dementia in this study was somewhat lower than that reported by other domestic and foreign studies. Our results related to the difference in time and space, diagnostic tools, response rates, and distribution of male and female subjects, etc.
Aged* ; Busan* ; Cognition Disorders* ; Dementia* ; Female ; Humans ; Male ; Prevalence* ; Psychometrics

Pro-oxidant properties of ascorbate have been studied with uses of brain tissues and neuronal cells. Here we address potential mechanism of ascorbate coupling with glutamate to generate oxidative stress, and the role which oxidized ascorbate (dehydroascorbate) transport plays in oxidative neuronal injury. Ascorbate in neurones can be depleted by adding glutamate in culture medium since endogenous ascorbate can be exchanged with glutamate, which enhances ascorbate/ dehydroascorbate transport by depleting ascorbate in the neurons with the glutamate-heteroexchange. However, ascorbate is known readily being oxidized to dehydroascorbate in the medium. Glutamate enhanced the dehydroascorbate uptake by cells via a glucose transporter (GLUT) from extracellular region, and cytosolic dehydroascorbate enhanced lipid peroxide production and reduced glutathione (GSH) concentrations. Iso-ascorbate, the epimer of ascorbate was ineffective in generating the oxidative stress. These observations support the current concept that the high rates of dehydroascorbate transport via a GLUT after the release of ascorbate by glutamate leads to peroxidation, the role of glutamate on ascorbate/ dehydroascorbate recycling being critical to induce neuronal death via an oxidative stress in the brain injury.
Animals ; Ascorbic Acid/analogs & derivatives/pharmacology ; Biological Transport/drug effects ; Cerebral Cortex/*drug effects/*metabolism ; Cytochalasin B/pharmacology ; Dehydroascorbic Acid/*metabolism ; Glutamic Acid/*pharmacology ; Glutathione/metabolism ; In Vitro ; Lipid Peroxidation/*drug effects ; Male ; Oxidation-Reduction/drug effects ; Oxidative Stress/drug effects ; Rats ; Rats, Sprague-Dawley ; Thiobarbituric Acid Reactive Substances/metabolism