Phenyl 2‐pyridyl ketoxime induces cellular senescence‐like alterations via nitric oxide production in human diploid fibroblasts

Yang, Kyeong Eun,Jang, Hyun‐,Jin,Hwang, In‐,Hu,Chung, Young‐,Ho,Choi, Jong‐,Soon,Lee, Tae‐,Hoon,Chung, Yun‐,Jo,Lee, Min‐,Seung,Lee, Mi Young,Yeo, Eui‐,J BLACKWELL PUBLISHING 2016 AGING CELL Vol.15 No.2

<P><B>Summary</B></P><P>Phenyl‐2‐pyridyl ketoxime (PPKO) was found to be one of the small molecules enriched in the extracellular matrix of near‐senescent human diploid fibroblasts (HDFs). Treatment of young HDFs with PPKO reduced the viability of young HDFs in a dose‐ and time‐dependent manner and resulted in senescence‐associated β‐galactosidase (SA‐β‐gal) staining and G2/M cell cycle arrest. In addition, the levels of some senescence‐associated proteins, such as phosphorylated ERK1/2, caveolin‐1, p53, p16<SUP>ink4a</SUP>, and p21<SUP>waf1</SUP>, were elevated in PPKO‐treated cells. To monitor the effect of PPKO on cell stress responses, reactive oxygen species (ROS) production was examined by flow cytometry. After PPKO treatment, ROS levels transiently increased at 30 min but then returned to baseline at 60 min. The levels of some antioxidant enzymes, such as catalase, peroxiredoxin II and glutathione peroxidase I, were transiently induced by PPKO treatment. SOD II levels increased gradually, whereas the SOD I and III levels were biphasic during the experimental periods after PPKO treatment. Cellular senescence induced by PPKO was suppressed by chemical antioxidants, such as N‐acetylcysteine, 2,2,6,6‐tetramethylpiperidinyloxy, and L‐buthionine‐(<I>S</I>,<I>R</I>)‐sulfoximine. Furthermore, PPKO increased nitric oxide (NO) production via inducible NO synthase (iNOS) in HDFs. In the presence of NOS inhibitors, such as L‐NG‐nitroarginine methyl ester and L‐NG‐monomethylarginine, PPKO‐induced transient NO production and SA‐β‐gal staining were abrogated. Taken together, these results suggest that PPKO induces cellular senescence in association with transient ROS and NO production and the subsequent induction of senescence‐associated proteins<B>.</B></P>

자바리, Epinephelus bruneus의 난 발생과 부화에 미치는 수온의 영향

양문호,최영웅,정민민,구학동,오봉세,문태석,이창훈,김경민,한석중,Yang, Moon-Ho,Choi, Young-Ung,Jung, Min-Min,Ku, Hag-Dong,Oh, Bong-Sae,Moon, Tae-Seok,Lee, Chang-Hoon,Kim, Kyong-Min,Han, Seock-Jung 한국발생생물학회 2007 발생과 생식 Vol.11 No.2

This study examined temperature effect in egg development and hatching of longtooth grouper, Epinephelus bruneus. Fertilized embryos was not growth after morula stage at $15^{\circ}C$, at 18, 21, 24 and $27^{\circ}C$, the required time from fertilized embryos to hatching were 70 h. 30 min., 44 h. 10 min., 29 h. 10 min. and 24 h. 30 min., respectively. The hatching rates at $24^{\circ}C$ were higher than the other conditions and the hatching was not occurred at $15^{\circ}C$. These results suggest that the water temperature range of egg development and hatching was $18{\sim}27^{\circ}C$. 이 연구는 실내 사육수조에서 자연산란 후 수정된 난을 대상으로 수온에 따른 난 발생속도와 부화율을 조사하였다. 부화에 이르기까지 각 수온조건에서 소요된 시간은 $15^{\circ}C$에서 상실기 이후 발생이 진행되지 않았고, 18, 21, 24, $27^{\circ}C$에서 각각 70시간 30분, 44시간 10분, 29시간 10분 그리고 24시간 30분이 소요되었다. 부화율은 $15^{\circ}C$에서 0%였고, 18, 21, 24 그리고 $27^{\circ}C$에서 각각 $8.3{\pm}1.2%$, $18.0{\pm}6.2%$, $24.0{\pm}4.0%$ 그리고 $17.0{\pm}7.2%$로 뚜렷한 차이 없이 $24^{\circ}C$에서 다소 높았고 21와 $27^{\circ}C$에서 비슷한 경향이었으며 $18^{\circ}C$에서 가장 낮게 나타났다. 이러한 결과에서 자바리의 난발생 수온범위는 $18{\sim}27^{\circ}C$로 제안된다.

요관압 상승시 신혈류량 조절에 prostaglandin이 미치는 효과

민영기,양훈모,김종규,이석호 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1

Higher ureteral pressure than in normal condition causes increase in renal blood flow (RBF) and partial impairment of the autoregulation of RBF. Higher ureteral pressure increased renal prostaglandin production, it is not clear whether or not it is also responsible for partial impairment of the autoregulation of RBF. Therefore, we investigated the role which prostaglandin play in the autoregulation of RBF, studying the interaction between ureteral pressure and RBF autoregulation may reveal the role of prostaglandin in tubuloglomerular feedback. For the purpose of this experiment, six anesthetized mongrel dogs were prepared for the measurements of RBF, mean systemic and renal arterial pressure (RAP) and the manipulation of ureteral pressure to 0 cmH20, 20 cmH20 and 40 cmH20. The autoregulation curves were determined during both control and elevation of the ureteral pressure, before and after the pretreatment with indomethacin, a cyclooxygenase inhibitor. The desired ureteral pressure was achieved by vertically elevating the water-filled reservoir connected to the ureteral catheter to 20 cm and 40 cm above the kidney level. In response to the elevation of the ureteral pressure, RBF increased from 167±11 ml/min to 185±8 ml/min, 204±11 ml/min respectively and the renal arterial pressure and the systemic arterial pressure didn't change significantly. During 0 mmHg of ureteral presure threshold pressure of RBF autoregulation was 59±3 mmHg. On the other hand, during 20 cmH20, 40 cmH20 of ureteral pressure, the autoregulation curves shifted upward and rightward from control, threshold pressure is elevated by 74±3 mmHg. The pretreatment of the dogs with indomethacin failed to affect the lower limit of RBF autoregulation during both control (63±5 mmHg) and the elevated ureteral pressure (77±5 mmHg). Since RBF failed to increase in response to the elevated ureteral pressure, RBF autoregulation curves obtained during the elevated ureteral pressure shifted only rightward from indomethacin control. The results indicate that the increased intrarenal level of prostaglandin by increased ureteral pressure or prostaglandin-induced vasodilation does not appear to bear any relation to the reduction in the autoregulatore capacity during elevated ureteral pressure. It seems that the partial impairment of the autoregulation during acute ureteral obstruction is due to the consumption of tubuloglomerular feedback mechanism at 0 mmHg of ureteral pressure and that prostaglandin is neither mediator nor effector of tubuloglomerular feedback mechanism.

Sound Analysis in an In Vitro Endotracheal Tube Model

( Young Sik Park ),( Young Wook Kee ),( Kwang Suk Park ),( Jin Woo Lee ),( Sang Min Lee ),( Jae Joon Yim ),( Chul Gyu Yoo ),( Young Whan Kim ),( Sung Koo Han ),( Seok Chul Yang1 ) 대한내과학회 2011 The Korean Journal of Internal Medicine Vol.26 No.4

Background/Aims: Complete endotracheal tube obstruction is a medical emergency, and partial occlusion causes increased breathing rates and failure to wean off mechanical ventilation. Partial occlusion may be underestimated due to the lack of proper detection methods. We tested whether the sound of an endotracheal tube could be used to detect an endotracheal tube obstruction using an in vitro model. Methods: An endotracheal tube was connected to a ventilator on one end and a test lung on the other. Sounds were recorded with a microphone located inside the endotracheal tube via a connector. During mechanical ventilation, we changed the endotracheal tube internal diameter from 5.0 to 8.0 mm and different grades of obstruction at different sites were used along the tube. Sound energy was compared among the different conditions. Results: The energy of endotracheal tube sounds was positively correlated with the internal diameter and negatively correlated with the degree of obstruction. The rate of decline in energy differed with obstruction location. When the obstruction was more distal, the rate of decline in endotracheal sound energy was more rapid. Conclusions: Changes in the sound of an endotracheal tube can be used to detect an obstruction. Further studies are needed for clinical application.

유아의 성별, 연령에 따른 체력 특성

전영남,양점홍,김수진,이성민 釜山大學校 附設 體育科學硏究所 2005 體育科學硏究所 論文集 Vol.21 No.2

The purpose of this study is to examine the characteristics of young children's fitness development in accordance with gheir gender and age, providing information necessary for an effective physical education instruction for young children's growth and development. For the purpose, this researcher selected total 257 young children from K Kindergarten located at K-gu in B Metropolitan City who consisted of 73 boys and 45 girls, both of were fully aged 4, and 83 boys and 56 girls, fully aged 5.......

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

미치광이풀 모상근 배양에서 Tropane Alkaloid 생산성 증진을 위한 최적 생물학적 엘리시터 선발

정희영,강승미,강영민,김용덕,양재경,정영관,최명석 Plant molecular biology and biotechnology research 2003 Plant molecular biology and biotechnology research Vol.2003 No.-

Scopolamine and hyoscyamine which belong to tropane alkaloids are the pharmaceutically valuable anticholinergic drugs. In order to increase the productivities, the effects of elicitation were investigated during hairy root cultures of Scopolia parviflora. Biotic elicitors originated from 3 fungi and 1 yeast were prepared as homogenate and supernatant and added to 3-week-old cultures. Both of homogenate and supernatant of Candida albicans elicitors increased the scopolamine production. The production of hyoscyamine was enhanced by homogenate of Fusarium solani and supematant of C. albicans. Most of the other fungal elicitors were also improved on the tropane alkaloid production compared to non-treatment. Among the elicitors tested, C. albicans was proved the optimal biotic elicitor on tropane alkaloids production. These results will be served mass production of tropane alkaloids by large-scale production.

노인의 Helicobacter pylori 재균율

박주상,홍원선,이영수,이은주,명승재,정훈용,양석균,김진호,민영일 대한노인병학회 2000 Annals of geriatric medicine and research Vol.4 No.3

단계적 온도 하강법을 이용한 췌도세포 냉동보존법

정인경,오승훈,김병준,양태영,이병완,하창영,노정현,정재훈,민용기,이명식,이문규,김광원 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.26 No.1

연구배경:최근 당뇨병의 새로운 치료법으로 시도되고 있는 췌도이식은 충분한 췌도수의 확보와 췌도생존율을 높이기 위한 면역억제제 사용이 제한점이 되고 있다. 본 연구의 목적은 이식 전 충분한 췌도 수의 확보를 위해 분리한 췌도를 냉동보존하는 방법을 확립하고 냉동보존한 백서 췌도세포의 시험관내 그리고 생체내 기능을 조사하였다. 방법:분리한 백서의 췌장소도를 48시간 배양한 후 한 시험관당 췌도세포 1000개씩 나누었다. 냉동보존은 6개의 시험관에 DMSO를 첨가한 후 초 냉각(supercooling), 핵화(nucleation)단계를 거친 후 99% isopropanol과 액체질소가 들어있는 dewer를 이용하여-0.25℃/분의 냉각속도로 -40℃까지 단계적으로 얼린후-70℃ 액체질소 탱크에 보관했다. 해동은 냉동시킨 vial들을 액체 질소 태으에서 꺼내 37℃ 항온조에 담가 급격히 해동시킨 후, 원심분리하여 상층액을 제거하고 각 vial에 0.75M sucrose 용액을 가한 후, 10% fetal calf serum이 함유된 RPMI 1640 media에서 배양하였다 각각 6개의 시험관에서 해동한 췌도들을 광학현미경 및 형광현미경하에서 췌도의 모양과 생존율에 대해 조사하고 인슐린 정적반응을 알아보았다. 또한 분리한 췌도를 냉동보존하지 않고 이식한 경우를 대조군(6마리)과 생체내 기능을 비교하였다. 결과:① 냉동보존후 획득한 췌도의 수와 생존율 해동후 획득한 췌도의 수는 해동시킨 당일날이 902±21, 24시간 배양 후에는 857±16, 72시간 후에는 817±18개로 점차 감소되었다. AO/PI 염색상 각 췌도의 생존율은 냉동 전을 100으로 하였을 때 해동당일, 24시간 후, 72시간 후가 각각 60±5, 80±5, 90±5%로 해동후 3일간 배양하였을 때 냉동전의 수준으로 회복하였다. ② 냉동보존후 췌도의 포도당에 대한 정적 인슐린 분비능:냉동직후 감소된 경향을 보였으나 해동후 3일간 배양한 췌도의 인슐린 분비는 냉동전과 통계적으로 의미있는 차이가 없이 냉동보존 전의 수준으로 회복되었다. ③ 냉동보존후 췌도의 포도당에 대한 동적 인슐린 분비능:냉동보존한 췌도를 해동후 3일째의 인슐린 동적 분비능은 냉동 전과 마찬가지로 자극 인슐린의 반응의 제1기와 2기가 잘 관찰되었다. ④ 냉동보존한 췌도세포 이식 후 혈당 변화:스트렙토조토신으로 유도된 당뇨병 쥐에 췌도이식 후 혈당은 냉동보존한 췌도이식군에서 대조군에 비해 혈당의 조절효과가 더 오래 지속되었다. 결론:소동물에서 단계적 온도 하강법을 이용한 췌도세포 냉동보존법을 확립하였으며 이는 기능, 구조 및 생존율에 큰 이상을 보이지 않았으므로 장차 사람의 췌도세포 동종이식시 부족한 췌도세포수를 극복하고 면역반응을 줄일 수 있는 매우 유용한 방법이 될 것으로 판단된다. Background : Although islet transplantation has been attempted to reverse the state of diabetes, achieving a critical number of islets and modulating the immune response limit the success of islet transplantation. Cryo-preservation of islets offers many important benefits for islet transplantation by collecting islets with a wide variety of HLA phenotypes and islet MHC expression. The aims of this study was to determine the optimal conditions for cryo-preservation by using a controlled cooling method and to evaluate in vitro and in vivo functional properties of the cryo-preserved islets. Methods : Collagenase-isolated, Ficoll-purified islets were cultured for 48 hours. They were aliquoted into freezing tubes (1000 islets per tube), equilibrated with 2M dimethyl sulfoxide (DMSO) in three steps, supercooled, nucleated, and controll-cooled at rate of 0.25℃/min to - 40℃ prior to storage at - 196℃. Rapid thawing and removal of DMSO with 0.75 M sucrose preceded 48 hour of culture and the morphology, viability, glucose-induced insulin secretion, and in vivo function of rats transplanted with cryopreserved islets was reexamined. Results : ① Recovery was 90.2±0.2%, 85.7±0.1% and 81.7±0.1% immendiately after, 24 hours and 72 hours after thawing respectively. The viability was 60±5%, 80±5%, 90±5% immediately after, 24 hours and 72 hours after thawing respectively. ② The glucose-stimulated-insulin secretion (GSIS) tended to decrease immediately after thawing, but GSIS increase to the level of pre-cryopreservation 72 hours after thawing. ③ The in dynamic GSIS, the first and the second phase of insulin secretion were well preserved in islets cultured for 72 hours after thawing. ④ The cryopreserved islets were cultured for 3 days and transplanted into renal sub-capsular space of streptozotocin (STZ) induced diabetic rats. The duration of normoglycemia in the STZ-induced diabetic rats transplanted with cryopreserved islets was significantly longer than of the fresh islets. Conclusion : The optimal condition of cryopreservation using the controlled cooling method was established in rat pancreatic islets. This cryopreservation method can be a feasible approach for human islet transplantation (J Kor Diabetes Asso 26:64~74, 2002).

비열 플라즈마 처리를 이용한 polystyrene, 소시지 케이싱, 그리고 훈제연어에서의 식중독균 저해

이한빛(Hahn-Bit Lee),노영은(Young-Eun Noh),양희재(Hee-Jae Yang),민세철(Sea Cheol Min) 한국식품과학회 2011 한국식품과학회지 Vol.43 No.4

PS 필름에 접종된 S. Typhimurium, E. coli 0157:H7, L. monocytogenes를 저해시킬 때 헬륨을 사용한 플라즈마 처리의 경우에는 S. Typhimurium이,헬륨과 산소를 동시에 사용한 플라즈마 처리의 경우에는 L. monocytogenes가 가장 많이 저해되었다. E coli 0157:H7과 L. monocytogenes는 헬륨과 산소를 함께 사용하여 풀라즈마 처리하였을 때 헬륨만 사용하였을 때보다 더 큰 저해를 보였다. 헬륨과 산소를 함께 사용한 비열 폴라즈마 처리는 L. monocytogenes가 소시지 케이싱이나 훈제연어에 감염되었 을 때보다 PS 필름에 감염되었을 때 L. monocytogenes를 더 효과적으로 저해시켜 감염된 재료에 따라 다른 저해 효과를 보여 주었다. 비열 폴라즈마 처리에 사용된 가스의 종류와 미생물이 감염된 재료는 그 처리의 항균 효과에 대한 평가에서 중요하게 고려되어야 할 것이다. 헬륨과 산소를 사용한 비열 플라즈마 처리는 공정 후 포장재에 감염된 L. monocytogenes를 효과적으로 저해할 수 있을 것으로 기대된다. The effects of nonthermal plasma treatments against Salmonella Typhimurium, Escherichia coli 0157:H7, and Listeria monocytogenes living on polystyrene (PS), sausage casings, and smoked salmon were investigated. Inoculated PS, casings, and salmon were treated with nonthermal plasma generated with helium (5 L/min) or with both helium (5 L/min) and oxygen (100 mL/min) at 60 Hz and 30 kVxm for 2, 5, or 10 min. S. Typhimurium exhibited the highest sensitivity to the helium-used treatment. The greatest reduction (3.9±0.8 log CFU/㎠) was observed with L. monocytogenes on PS after the treatment with the mixed gas for 5 min. The treatment with the mixed gas inhibited L. monocytogenes on casings and salmon by 0.5±0.3 log CFU/cm: and 1.0±0.3 log CFU g, respectively. Different treatment times did not result in different reductions of L. monocytogenes on both casings and salmon. The types of treatment gas and material of contamination need to be considered for evaluating the antimicrobial effects of nonthermal plasma treatments.