• Journal of Korean Neurosurgical Society
• /
• v.62 no.2
• /
• pp.243-255
• /
• 2019

Objective : Although traumatic brain injury (TBI) occurs in people of all age groups, the elderly population is at a particular risk. The proportion of elderly population in the society is markedly increasing and Korea is one of the most rapidly aging societies. Here, we analyzed the data from 904 patients older over 65 years who were registered in the Korean Neuro-Trauma Data Bank System (KNTDBS). Methods : The Korean Society of Neurotraumatology recorded data from 20 institutions between September 2010 and March 2014. This retrospective study examined the clinical epidemiology, sex difference, outcome epidemiology, sociodemographic variables, and outcomes in the geriatric population related to TBI based on data from the KNTDBS. Results : The study included 540 men and 364 women. The age distributions in the male and female groups were statistically significantly different. The most common cause of trauma was a fall and diagnosis was acute subdural hematoma. The incidence was the highest in men aged 80-84 years and in women aged 75-79 years. The most common time of arrival to hospital after TBI was within 1 hour and 119 rescue team provided first aid earliest to patients with TBI. The mortality rate stratified according to the cause of trauma was significantly different, with mortality rates of 3.77% in fall and 11.65% in traffic accident. The mortality rates according the severity of brain injury, Glasgow Coma Scale score, and treatment were statistically significant. Conclusion : To our knowledge, this study is the first to focus on elderly patients with TBI in Korea and particularly investigate mortality and characteristics related to TBI-related death based on data from the KNTDBS. Although the study has some limitations, our results may be used to obtain useful information to study targeted prevention and more effective treatment options for older TBI patients and establish novel treatment guidelines and health polish for the geriatric population.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.38 no.1
• /
• pp.22-26
• /
• 2024

The purpose of this study was to identify the applicability, main compounds, and target genes of Cnidii Fructus (CF) in the treatment of gastritis using network pharmacology. The compounds in CF were searched in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine (TM-MC). The target gene information of the compounds was collected from pubchem and cross-compared with the gastritis-related target gene information collected from Genecard to derive the target genes. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on the derived target genes. Afterwards, network analysis between compounds and disease target genes was performed using cytoscape. We identified 121 active compounds and 139 target genes associated with gastritis. Pathways derived from the GO biological process and KEGG pathway DB primarily focus on target genes related to inflammation (IL-6, IL-8, TNF production, NF-κB transcription factor activity, and NF-κB signaling pathway) and cell death (PI3K-Akt, FoxO). Major targets for CF treatment of gastritis include TP53, TNF, BCL2, EGFR, NFKB1, ABCB1, PPARG, PTGS2, IL6, IL1B, and SOD1, along with major compounds such as coumarin, osthol, hexadecanoic acid, oleic acid, linoleic acid, and stigmasterol. This study provided CF's applicability for gastritis, related compounds, and target information. Evaluating CF's effectiveness in a preclinical gastritis model suggests its potential use in clinical practice for digestive system diseases.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.17 no.6
• /
• pp.1383-1392
• /
• 2003

Apoptosis is a morphologically and biochemically district form of cell death that occurs in many different cell types in a wide variety of organisms. Albizzia julibrissin belonging the family Leguminosae has been used for the treatment of contusion, sore throat, amnesia, and insomnia in oriental traditional medicine. This study investigates whether the water extract of A. julibrissin induce apoptotic cell death in Jurkat T-acute lymphoblastic leukemia (ALL) cells. Jurkat cells were increased inhibitions of cell viability in a concentration-dependent manner by A. julibrissin. This herbal medicine also caused apoptosis as measured by cell morphology and DNA fragmentation. The capability of A. julibrissin to induce apoptosis was associated with proteolytic cleavage of specific target proteins such as poly (ADP-ribose)polymerase (PARP) and beta-catenin proteins suggesting the possible involvement of caspases. Our result showed that Bcl-2 and Bax protein levels were not changed in all A. julibrissin-treated groups compared to control group. These results suggest that A. julibrissin-mediated apoptosis is independent with Bcl-2 related signaling pathway in this cells. The purpose of the present study is also to investigate the Effect of A. julibrissin on cell cycle progression. Our results showed that G1 checkpoint related gene products (cyclin D1, cyclin dependent kinase 4, retinoblastoma, E2F1) were decreased in their protein levels in a dose-dependent manners after treatment of the extract. These results indicate that the increase of apoptotic cell death by A. julibrissin may be due to the inhibition of cell cycle progression in wild type p53-lacking Jurkat cells.

• Archives of Pharmacal Research
• /
• v.24 no.2
• /
• pp.136-143
• /
• 2001

Fumonisins are specific inhibitors of ceramide synthase in sphingolipid metabolism. An alteration in sphingolipid metabolism as a result of fumonisin exposure is related to cell death (Yoo et al., 1992). The objective of this study was to investigate whether elevated free sphinganine levels are related to the sensitivity of cultured cells to fumonisin exposure. Fumonisin $B_1$ elevated the intracellular free sphinganine concentraions in both LLC-$PK_1$ and Chinese hamster ovary (CHO) cells. However, CHO cells are resistant to fumonisin cytotoxicity at 50${u}m$, while LLC-$PK_1$ cells are sensitive at concentrations greater than 357M. The intracellular concentration of free sphinganine in LLC-$PK_1$ cells treated at 50${u}m$ fumonisin $B_1$ for 72 h was approximately 1450 pmol/mg protein relative to the 37 pmol observed in the control culture. Under the same conditions, the population of apoptotic cells in the 50${u}m$ fumonisin $B_1$-treated culture was approximately 37% of the total compared to 12% in the control. The caspase III-like activity after 72 h in the 50${\mu}$M fumonisin $B_1$-exposed culture Increased to approximately 50 $pmol/mg$ protein/hr compared to 6 $pmol/mg$ protein/hr in the control. L-cycloserine, a serine palmitoyltransferase inhibitory reduced the fumonisin $B_1$-stimulated caspase III-like activity down to the control level. Under the same culture conditions, the intracellular concentration of free sphinganine after-cycloserine plus fumonisin $B_1$ treatment was 140 pmol/mg protein compared to 1450 $pmol/mg$ protein in fumonisin $B_1$ alone. The intracellular concentration of free sphinganine in CHO cells treated with 50${u}m$ fumonisin $B_1$ for 72 h was al)proximately 460 pmol/mg protein, indicating that the mass amount of elevated free sphinganine in the CHO cells was about 32% of that in LLC-$PK_1$ cells. Adding exogenous sphinganine to the CHO cells along with 50${u}m$ fumonisin $B_1$ treatment for 72 h caused both necrosis and apoptosis. In conclusion, the elevated endogenous sphinganine acts as a contributing factor to the fumonisin-induced cell death.

• Journal of Chest Surgery
• /
• v.9 no.2
• /
• pp.198-206
• /
• 1976

A Total of Forty eight patients underwent open-heart surgery for correction of tetralogy of Fallot at the Seoul National University Hospital from January 1974 to October 1976, with an overall survival rate of 77 per cent. Operative mortality varied according to severity of the lesion, age of the patient, nature of previous surgical treatment and presence or absence of an outflow tract patch across the pulmonary valve ring. Eleven patients died in the early postoperative period and thirty seven patients were discharged from the hospital alive. A patch of the right ventricular outflow tract and pulmonary annulus was required to relieve pulmonic stenosis in 24 patients. There were 10 deaths in this group (42%) as compared to 1 death in the group of 24 patients who were corrected without a patch. Operative mortality was especially higher when an inlay patch was placed across the pulmonary valve ring. This may be related to the possibly greater anatomic severity of these cases and to the longer operating time when a patch was used. The electrocardiogram showed right ventricular hypertrophy in 35 cyanotic patients. Intraventricular conduction was normal in 34 patients before operation. It was normal postoperatively in only 5 of 34 patients in this group who survived surgery. Complete right bundle branch block appeared at operation in 21 patients, and 8 patients developed incomplete right bundle branch block. Major causes of death were progressive cardiac failure (4), Complete atrioventricular dissociation (3), bleeding (2), cardiac tamponade (1), and sudden cardiac arrest (1)

• Biomolecules & Therapeutics
• /
• v.4 no.4
• /
• pp.402-407
• /
• 1996

Effects of oxidative stress on the induction of apoptosis and the activity of antioxidant enzymes were investigated in HL-60 cells using $H_2O$$_2$and cisplatin which generate oxygen species in the cell. Various concentrations of oxidants were treated to cells and at different incubation time, cells were harvested for assays. Cell viability, morphology by propidium iodide staining and DNA fragmentation by agarose gel electrophoresis were observed to determine whether they induce apoptosis. The activity of antioxidant enzymes such as superoxide dismutase and catalase was also measured to evaluate the cellular response to the oxidative damage. The results are as follows: $H_2O$$_2$ induced apoptosis at 10 $\mu$M after 6h incubation, while it took 12h for cisplatin. Both oxidants induced the superoxide dismutase activity at a tolerable low concentration. However, at a concentration which causes apoptotic cell death, the enzyme level was dropped markedly at first and then recovered to the normal level after which it declined again, probably due to cell death. On the other hand, changes in the activity of catalase were not significant at most concentrations except the statistically significant decrease at 24h after 10 $\mu$M-$H_2O$$_2$treatment. In this study, $H_2O$$_2$- and cisplatintreated cells showed similar results in apoptotic response and enzyme activities, suggesting that anticancer activity of cisplatin may be related, at least in part, to the production of oxygen free radicals.

• Journal of Life Science
• /
• v.21 no.2
• /
• pp.316-321
• /
• 2011

Generation of tryptophan-derived metabolites by indoleamine 2,3-dioxygenase (IDO) is a potent immunoregulatory mechanism in T cell responses. However, the mechanism remains unclear. We showed that 3-hydroxyanthranilic acid (3-HAA), the most potent metabolite, selectively induced apoptosis in activated T cells, but not in resting T cells. This was not associated with cell cycle arrest. We found that TRAIL expression was selectively induced in activated T cells by treatment of 3-HAA. Blockade of the TRAIL: DR4/DR5 pathway significantly inhibited 3-HAA-mediated T cell death. Our data suggest that TRAIL-induced apoptosis is involved in the mechanism of 3-HAA-mediated T cell death.

• Journal of Life Science
• /
• v.24 no.9
• /
• pp.927-934
• /
• 2014

Sanguinarine, a benzophenanthridine alkaloid originally derived from the root of Sanguinaria canadensis, has been shown to possess antimicrobial, antioxidant, and anti-cancer properties. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in cancer cells, but not most normal cells and has shown efficacy in a phase 2 clinical trial, development of resistance to TRAIL by tumor cells is a major roadblock. Our previous study indicated that treatment with TRAIL in combination with subtoxic concentrations of sanguinarine sensitized TRAIL-mediated apoptosis in TRAIL-resistant human gastric carcinoma AGS cells; however, the detailed mechanisms are not fully understood. In this study, we show that sanguinarine sensitizes AGS cells to TRAIL-mediated apoptosis as detected by MTT assay, agarose gel electrophoresis, chromatin condensation and flow cytometry analysis. Combined treatment with sanguinarine and TRAIL effectively induced expression of death receptor (DR) 5 but did not affect expression of DR4 and mitogen activated protein kinases signaling molecules. Moreover, the combined treatment with sanguinarine and TRAIL increased the generation of reactive oxygen species (ROS); however, N-acetylcysteine, ROS scavenger, significantly recovered growth inhibition induced by the combined treatment. Taken together, our results indicate that sanguinarine can potentiate TRAIL-mediated apoptosis through upregulation of DR5 expression and ROS generation.

• Journal of agricultural medicine and community health
• /
• v.18 no.1
• /
• pp.43-54
• /
• 1993

In order to find the factors associated with the death of hypertensives, 12 year follow-up study for 267 hypertensives whose average blood pressure were 140/90 mmHg or above during their first health screening in 1979-1980 at YongJin Township, Wanju Country, North Cholla Province by the Community Health Team of Chonju Presbyterian Medical Center. The study results are as follows : 1. Initial general characteristics of hypertensives were studied. The age distribution of studied hypertensives showed 27.3% in 40-49 years, 25.8% in 50-59 years, 29.6% in 60-69 years and 17.2% In 70 + years old group. Marital status showed that 82.8% of hypertensives had their wife or husband. 74. 5% were employed on agriculture. 56.5% of hypertensives were illiterate. 2. Among the hypertensives, 91.6% of male and 22.8% of female reported that they were smokers. 82.6% of hypertensives had body mass index lower than 25 Kg/$m^2$. 46.8% of average systolic blood pressure were 160mmHg or above and 54.3% of average diastolic blood pressure were 95mmHg or above. 3. Twenty percent of hypertensives reported that they were treating hypertension at the beginning of follow up, while 68.5% reported that they were not treated. 28.1% reported that they were treating hypertension within 6 months before last follow-up. but 69.3% reported that they were not treated for hypertension within Ii months before last follow up. So 50.6% were classified as never treated group and 41.2% as treated group. 4. Average blood pressure for initial 3 years were calculated. The change of average systolic blood pressure was observed as $161.3{\pm}19.4mmHg$ at the first year, $145.6{\pm}28.0mmHg$ at the second year and $141.4{\pm}37.2mmHg$ at the third year. Average diastolic blood pressure were changed from $96.2{\pm}14.4mmHg$ at the first year to $90.6{\pm}18.6mmHg$ at the second year and $86.4{\pm}22.9mmHg$ at the third year. 5. By the follow-up of hypertensives, 54 hypertensives (46.2%) among 117 male hypertensives and 50 hypertensives (33.3%) among 150 female hypertensives died for 12 years. 42.6% of male death and 52.0% of female death were caused by cerebrovascular diseases. 6. Through univariate statistical test about the association between general characteristics or cardiovascular risk factors of hypertensives and mortality for 12 years, age variable among male and among female age, marital status, occupation. educational level. systolic blood pressure and treatment status were shown as significant variable to influence upon the mortality. 7. By multiple logistic regression analysis, among male age and systolic blood pressure were selected as significant variable to be associated with the total mortality for 12 years. Among female age, systolic blood pressure and treatment status were selected as statistically significant variable to be associated with the total mortality for 12 years.

• Biomolecules & Therapeutics
• /
• v.21 no.1
• /
• pp.29-34
• /
• 2013

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family of cytokines. TRAIL selectively induces apoptotic cell death in various tumors and cancer cells, but it has little or no toxicity in normal cells. Agonism of TRAIL receptors has been considered to be a valuable cancer-therapeutic strategy. However, more than 85% of primary tumors are resistant to TRAIL, emphasizing the importance of investigating how to overcome TRAIL resistance. In this report, we have found that nemadipine-A, a cell-permeable L-type calcium channel inhibitor, sensitizes TRAIL-resistant cancer cells to this ligand. Combination treatments using TRAIL with nemadipine-A synergistically induced both the caspase cascade and apoptotic cell death, which were blocked by a pan caspase inhibitor (zVAD) but not by autophagy or a necrosis inhibitor. We further found that nemadipine-A, either alone or in combination with TRAIL, notably reduced the expression of survivin, an inhibitor of the apoptosis protein (IAP) family of proteins. Depletion of survivin by small RNA interference (siRNA) resulted in increased cell death and caspase activation by TRAIL treatment. These results suggest that nemadipine-A potentiates TRAIL-induced apoptosis by down-regulation of survivin expression in TRAIL resistant cells. Thus, combination of TRAIL with nemadipine-A may serve a new therapeutic scheme for the treatment of TRAIL resistant cancer cells, suggesting that a detailed study of this combination would be useful.