• Journal of Korean Neurosurgical Society
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• 제62권2호
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• pp.243-255
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• 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.

• 동의생리병리학회지
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• 제38권1호
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• pp.22-26
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• 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.

• 동의생리병리학회지
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• 제17권6호
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• pp.1383-1392
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• 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
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• 제24권2호
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• pp.136-143
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• 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
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• 제9권2호
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• pp.198-206
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• 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
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• 제4권4호
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• pp.402-407
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• 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.

• 생명과학회지
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• 제21권2호
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• pp.316-321
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• 2011

Indoleamine 2,3-dioxygenase (IDO)에 의한 트립토판 대사체의 생성은 T 세포에 강력한 억제효과를 미치지만 여전히 그 작용기전에 대한 연구보고는 미비한 실정이다. 본 연구자는 트립토판 대사체 3-HAA가 선택적으로 활성 T 세포의 사멸을 촉진시키는 효과가 있음을 확인하였고, 이는 세포주기 억제와는 관련이 없었다. 3-HAA 처리 시 활성 T 세포에서 TRAIL과 그의 수용체의 발현이 현저히 증가하고, 이들 상호작용을 차단하였을 때 3-HAA-매개 활성 T 세포사멸 효과가 유의하게 낮아졌다. 본 연구를 통해 트립토판 대사체 3-HAA의 선택적 T 세포 억제 효과가 TRAIL-유도 세포사멸과 관련됨을 알 수 있다.

• 생명과학회지
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• 제24권9호
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• pp.927-934
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• 2014

혈근초(Sanguinaria canadensis) 뿌리에서 유래된 benzophenanthridine alkaloid의 일종인 sanguinarine은 항균, 항산화 및 항암작용 등 다양한 생리활성을 지니고 있는 것으로 알려져 있다. 비록 TRAIL이 암세포에서는 apoptosis를 유도하지만 정상세포에서는 세포독성을 나타내지 않는다는 큰 장점으로 제 2 임상 단계에서 유의적인 성과를 이루었지만, TRAIL 저항성을 극복해야 하는 큰 어려움이 남아있다. 본 연구실에서는 TRAIL이 세포독성을 나타내지 않는 범위의 sanguinarine과 혼합처리에 의하여 TRAIL 저항성 AGS 위암세포에서 apoptosis를 유발하였음을 보고한 바 있으며, 본 연구에서는 sanguinarine의 TRAIL 저항성 관련 극복에 대한 추가적인 기전 연구를 실시하였다. 본 연구의 결과에 의하면, sanguinarine과 TRAIL의 혼합처리는 각각의 단독 처리에 비하여 AGS 세포의 증식억제 및 apoptosis 유도의 상승 효과가 있었으며, 이를 MTT assay, agarode gel 전기영동, 염색질 응축 현상 및 flow cytometry 분석을 통하여 확인하였다. 또한 sanguinarine과 TRAIL의 혼합처리는 DR5의 발현을 증가시켰으며, ROS의 생성을 촉진시켰다. 그러나 동일 조건에서 MAPKs 신호 전달계에는 큰 영향을 주지 않았다. 아울러 ROS 생성을 인위적으로 차단하였을 경우, sanguinarine과 TRAIL의 혼합처리에 의한 생존도 저하가 유의적으로 회복되었다. 이러한 결과는 sanguinarine과 TRAIL이 DR5의 발현 증가와 ROS의 생성을 촉진시킴으로서 apoptosis 신호를 활성화하였음을 의미하는 결과로서 TRAIL 저항성 극복을 위한 sanguinarine 활용의 유용성을 보여주는 것이다.

• 농촌의학ㆍ지역보건
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• 제18권1호
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• pp.43-54
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• 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
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• 제21권1호
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• pp.29-34
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• 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.