Furosemide에 의한 소디움 운반체 발현의 변화

오윤규 ( Yoon Kyu Oh ),나기영 ( Ki Young Na ),이재욱 ( Jay Wook Lee ),장혜련 ( Hye Ryun Chang ),박영선 ( Young Sun Park ),박정환 ( Jung Hwan Park ),주권욱 ( Kwon Wook Joo ),김근호 ( Gheun Ho Kim ),이정상 ( Jung Sang Lee ),한진석 ( 대한신장학회 2003 Kidney Research and Clinical Practice Vol.22 No.2

배경 : 임상에서 흔히 사용하는 이뇨제 furosemide는 비후상행각에서 Na+-K+-2CI- cotranspoter (NKCC2)를 억제하여 NaCl 재흡수를 차단하여 이뇨작용을 나타낸다. Furosemide를 장기간 투여하면 내성과 대사성 알카리증의 부작용이 발생할 수 있는데, 이는 집합관에 도달하는 소디움 증가와 관련 있을 가능성이 있다. 방법 : 저자들은 furosemide의 내성이나 부작용이 집합관 상피 소디움 통로 (ENaC) 단백발현의 변화와 관련이 있는지를 확인하고자, Sprague-Dawley rat에서 farosemide (12 mg/day)을 7일간 지속적 피하 주입한 후 반정량적 immunoblotting과 면역조직화학법을 이용하여 NKCC2, Na +-CL- cotransporter (NCC), ENaC 단백의 발현을 관찰하였다. 실험기간 동안 수분과 전해질 용액 (0.8% NaCl & 0.1% KCl)을 자유롭게 섭취하도록 하여 체액 감소를 방지하였다. 결과 : 부형약 (vehicle)을 투여한 대조군에 비하여, furosemide를 투여한 군에서 각각 요량과 요 소디움 배설이 증가하였으나, 체중, 혈청 알도스테론치 및 크레아티닌 청소율은 차이가 없었다. Furosemid 투여 후 NKCC2 단백은 피질 (151±10 vs. 100±10%, p<0.05)과 외수질 (122±5 vs. 100±3%, p<0.01)에서 증가해 있었다. ENaC 단백은 세 가지 subunit 모두 furosemide 투여 후 대조군에 비하여 피질 (α:187±25 vs. 100±22%, p<0.05; β:155±8 vs. 100±15%, p<0.05; γ:168±16 vs. 100±9%, p<0.05)과 외수질 (α:171±27 vs. 100±17%, p<0.05; β :986±91 vs. 100±33%, p<0.01; γ :242±24 vs. 100±22%, p<0.01)에서 증 가하였다. 면역조직화학법에서도 furosemide를 투여한 군의 집합관 주세포에서 ENaC β-subunit가 더 강하게 염색되었다. 결론 : 이상에서 장기간 furosemide 투여시 집합관 ENaC 발현이 증가하며, 이러한 원위부네프론의 적응 반응이 이뇨제 내성을 유발하는데 기여할 것으로 생각한다. Background : Furosemide inhibit NaCl absorption in the thick ascending limb and produce an increase in distal delivery of Na+. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic furosemide infusion is associated with compensatory increases in the abundance of Na+ transporters in distal nephron. Methods : Osmotic minipumps were implanted into Sprague-Dawley rats to deliver 12 mg/day of furosemide(n=6) with simultaneous administration of 0.8% NaCl and 0.1% KCl in drinking water for 7days. Results : Compared with vehicle infused controls, urine volume and urine sodium amount were increased. However, there were no differences in body weight, serum aldosterone, and creatinine clearance. The abundance of Na+-K+-2CI - cotransporter after furosemide infusion was increased in cortex (151±10 vs. 100±10%, p<0.05) and outer medulla (122±5 vs. 100±3%, p<0.01). In furosemide infusion group, the abundance of all three subunits of epithelial sodium channel (ENaC) was increased both in cortex (α:187±25 vs. 100±17%, p<0.05; β:155±8 vs. 100±15%, p<0.05; γ :168±16 vs. 100±9%, p<0.05) and outer medulla (α:171±27 vs. 100±17%, p<0.05; β :986±91 vs. 100±33%, p<0.01; γ :242±24 vs. 100±22%, p<0.01). Consistent with these results, ENaC β-subunit immunohistochemistry showed a remarkable increase in immunoreactivity in the principal cells of collecting ducts with furosemide treatment. Conclusion : These increases in the abundance of ENaC protein may account for the generation of diuretic tolerance.

The Efficacy and Safety of 4-n-butylresorcinol 0.1% Cream for the Treatment of Melasma: A Randomized Controlled Split-face Trial

( Sun Young Huh ),( Jung Won Shin ),( Jung Im Na ),( Chang Hun Huh ),( Sang Woong Youn ),( Kyoung Chan Park ) 대한피부과학회 2010 Annals of Dermatology Vol.22 No.1

Background: Melasma is a common acquired symmetrical hypermelanosis that occurs on sun-exposed areas, and it is frequently observed among women. Various treatment modalities have been tried, but none are completely satisfactory. 4-n-butylresorcinol, which is a resorcinol derivative that has an inhibitory effect on both tyrosinase and tyrosinase-related protein-1, was introduced in 1995 and it has received increasing attention as a new hypopigmenting agent. However, the hypopigmenting effect of 4-n-butylresorcinol in human subjects has only been shown in a few studies. Objective: The aim of this study was to investigate the hypopigmenting efficacy and safety of 4-n-butylresorcinol 0.1% cream for the treatment of melasma. Methods: Twenty patients with melasma were enrolled to this randomized, double-blind, vehicle-controlled, split-face comparative study. The patients were instructed to apply 4-n-butylresorcinol 0.1% cream or vehicle to each side of the face twice daily for 8 weeks. Mexameter measurements were performed along with photography at baseline, 4 weeks and 8 weeks. Adverse events were observed and recorded throughout the study. Results: All the patients completed the study. Mexameter measurements demonstrated that the melanin index of the treated side showed a significant decrease when compared with that of the vehicle-treated side after 4 weeks (p=0.006) and after 8 weeks (p<0.0005). All the adverse reactions were mild and transient. Conclusion: 4-n-butylresorcinol 0.1% cream showed rapid efficacy and it was well tolerated when used for the treatment of melasma. (Ann Dermatol 22(1) 21∼25, 2010)

Characteristics of Cytosolic Calcium-Independent Phospholipase A2 Isolated from Rat Liver

Na, Doe Sun,Park, Young Min,Rhee, Hae Jin,Won, Jong Hak 생화학분자생물학회 1997 BMB Reports Vol.32 No.2

A calcium-independent phospholipase A₂ (iPLA₂) was identified from the cytosolic fraction of rat liver cells. On gel filtration chromatography, the iPLA₂ activity was eluted as broad peaks of 150 to 500 kDa. The enzyme was maximally active at pH 7.5, retained 75% of its original activity after heating at 50℃ for 5 h, and was inhibited by Ca^(2+), Mg^(2+), and Zn^(2+) ions, but was not affected by Na+ and K+ ions. The enzymatic activity was increased up to 150% by 1 to 4 mM DTT and was inhibited up to 25% by 0.1 to 1 mM PMSF. The iPLA₂ activity had preference for the head group of phospholipass, where phosphatidylethanolamine was preferred to phosphatidylcholine. The results suggest that the iPLA₂ may be a novel enzyme distinct from the previously reported iPLA₂s.

Structural basis for the ATP-independent proteolytic activity of LonB proteases and reclassification of their AAA+ modules.

An, Young Jun,Na, Jung-Hyun,Kim, Myung-Il,Cha, Sun-Shin Microbiological Society of Korea 2015 The journal of microbiology Vol.53 No.10

<P>Lon proteases degrade defective or denature proteins as well as some folded proteins for the control of cellular protein quality. There are two types of Lon proteases, LonA and LonB. Each consists of two functional components: a protease component and an ATPase associated with various cellular activities (AAA+ module). Here, we report the 2.03 -resolution crystal structure of the isolated AAA+ module (iAAA+ module) of LonB from Thermococcus onnurineus NA1 (TonLonB). The iAAA+ module, having no bound nucleotide, adopts a conformation virtually identical to the ADP-bound conformation of AAA+ modules in the hexameric structure of TonLonB; this provides insights into the ATP-independent proteolytic activity observed in a LonB protease. Structural comparison of AAA+ modules between LonA and LonB revealed that the AAA+ modules of Lon proteases are separated into two distinct clades depending on their structural features. The AAA+ module of LonB belongs to the -H2 & Ins1 insert clade (HINS clade)- defined for the first time in this study, while the AAA+ module of LonA is a member of the HCLR clade.</P>

忠南 錦山郡 西臺山 一帶의 나비目 昆蟲相

남상호,조영호,장석원,박영준,이선영,나선희 대전대학교 기초과학연구소 2002 自然科學 Vol.13 No.2

충청남도 금산군 서대산 일대의 나비목 곤충상을 조사한 결과 22과 344종 1,936개체가 조사되었다. 이중 밤나방과가 102종 589개체, 자나방과가 67종 440개체로 이 2과가 전체의 50%이상을 차지하였다. 자나방과의 두줄가지나방은 1,936 개체중 85개체가 채집되어 4.4%의 가장 높은 우점도를 나타냈다. 월별 우점종은 4월 노랑무늬물결자나방, 5월 별박이세줄나비, 6월 목도리불나방, 7월 청백무늬밤나방, 8월 두줄가지나방, 9월은 털뿔가지나방이 조사되었다. 월별 종다양도는 4월 2.95, 5월 3.37, 6월 4.63, 7월 4.62, 8월 4.23, 9월은 2.97이었으며, 평균 종다양도는 3.80으로 서대산 일대의 나비목 곤충상은 비교적 양호한 편으로 조사되었다. This study was carried out to investigate Lepidopterous insect fauna from Mt. Seodae in Geumsan-gun, Chungnam. The samples were collected from April to September in 2001. Total 1,936 individuals belonging to 344 species, 22 families of Lepidoptera were collected. The sum of individuals belonging to Noctuidae and Geometridae exceed 50% of the collected samples in that Noctuidae was consisted of 102 species 589 individuals and Geometridae was 67 species 440 individuals. The dominant species in surveyed area was Rikiosatoa grisea of Geometridae, the dominant species by month were Idiotephria amelia in April, Neptis pryeri in May, Paraona staudinger in June, Ercheia niveostrigata in July, Rikiosatoa grisea in August and Alcis angulifera in September respectively. Species diversity indices by month were 2.93 in April, 3.37 in May, 4.63 in June, 4.62 in July, 4.23 in August and 2.97 in September respectively. Mean species diversity index was 3.80.

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.

신이식에서 이식신의 생존분석

오선미,김종학,황평주,구영선,강민규,나기량,김종섭,김성숙,이강욱,신영태,설종구,배진선,손기섭 충남대학교 의과대학 지역사회의학연구소 1997 충남의대잡지 Vol.24 No.2

To investigate the prognostic factors for the survival of transplanted kidney in patients with end-stage renal failure, 59 cases of renal transplantation from September 1986 to Feburary 1997 in Chungnam National University Hospital were analyzed retrospectively. The results were as follows: 1)The mean age of recipients was 33.8 years and that of doners was 38.9 years. The male to female ratio of recipients was 2.5:1, and that of donors was 1.03:1 2) Living related donore(LRD) were 79.6% and living non-related donors were 20.3%. The HLA-identical donors(ID) in LRD were 18.7% and HLA-haploidentical donors(HID) were 61.0%. In living non-related donors(LNRD), mean matched HLA-AB antigens were 1.56 and mean matched HLA-DR antigens were 0.56. 3) The average 5-year patient survival fate was 94%, and average 5-year graft survival rate was 70%. The 5-year graft survival fate of HLA-ID was 100%, and those HLA-HID and LNR were 70% and 36% respectively. 4) Total 33 episodes of acute rejection were found in 45.8% of transplanted patients. The number of acute rejection episode did not show significant difference between LRD and LNRD(P > 0.05). There was no significant difference in MLC between two groups(p > 0.05). 5) In comparison between the 18 patients who lost their graft function in 5 years and 17 patients who are maintaining graft function for more than 5 years, MLC was significantly lower in patients with functioning graft than of patients with non-functioning graft (p < 0.05). The number of rejection episode was also lower in patients with functioning graft than that of the patients with non-functioning graft(p < 0.05). However, there were no significant difference in recepient and donor age and history of pre-transplantation donor specific transfusion between two groups. With the results above, we can speculate that adequate donor selection according to good matched HLA typing and low MLC is very important for graft survival in renal transplantation. Prevention and treatment of acute rejection in renal transplantation is also na important factor for graft survival.

대학부속병원 응급실에 내원한 청소년 정신장애 환자의 특성

나철,김헌수,민병근,김영돈,이재우,박재선,김민호,이길홍 중앙대학교 의과대학 의과학연구소 1987 中央醫大誌 Vol.12 No.4

The authors respectively reviewed their records from 100 visits by adolescents and 100 visits by adults chosen by random sampling from all adolescent and adult patients seen during July 1984 and July 1987 in the emergency room of Chung-Ang University, Young-San Hospital.Chi-square statistics were calculated with Yates' correction. The results were as follows: 1. Adolescent patients were tended to be more likely than adults to have been referred by friends. 2. Adolescent patients were more likely than adults to have visited emergency room promptly after symptom oneset, and less likely to have insight about one's mental illness.Adolescent were less likely to receive neuropsychiatric out-patient treatment plan, in spite of psychiatrist's recommendation, because of low insight level. 3. With regard to their symptoms and chief complaints, adolescent patients more pften reported anger, aggressive behavior and sucide attempts, while adults were more likely to have been sucide idea. 4. The precipitant for the current visit was more likely to have been extra-familial difficulties inculding academic problem and bad relationdhip with peer groups for adolescents and intrafamiliai problems such as loss of loved person and primary interpersonal relation difficulties for adults. 5. Both gruops were more likely to be diagnosed as suffering from somatization disorder. Adult patients were mpro likely than adolescents to be diagnosed as affective disorder, especially atypical depression. 6. Both groups frequently abused some substances, with adolescents tending to use dyuga and adults tending to use alcohol. In conclusion frequently patients coming to the emergency room had acute and serious pathology, because anger, aggressive brhavir, self0destructive behavior and sucide attempts were expressed vividly and explosively.

원전 고등제어 알고리즘 설계를 위한 소규모 시뮬레이터 개발

나만균,심영록,신선호,노희천 조선대학교 에너지.자원신기술연구소 2003 에너지·자원신기술연구소 논문지 Vol.25 No.2

There has been a difficulty in implementing control algorithms (including even proportional-integral-derivative control algorithms) designed to verify and test to many small-scale simulators. In particular, it was almost impossible to implement advanced control algorithms to them. Therefore, it is required to develop a new simulator that facilitates the implementation of advanced control algorithms and the interface between different kinds of application programs. The objective of this work is to improve the existing small-scale simulator (FISA-2/WS) for the Kori unit 2 nuclear power plant and thus enable advanced control algorithms to be tested and verified by being applied to it. The developed simulator consists of FORTRAN, Visual C++, and MATLAB programs and an advanced control method using a receding horizon control method was applied to it to control the steam generator water level.

일측 요관폐쇄에 의한 실험적 수신증에서 신조직내 MCP-1 및 TNF-α유전자 발현

나가량,황평주,김종학,구영선,강민규,서광선,이강욱,신영태 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.2

Early cellular and molecular derangements have been suggested as potential pivotal factors for the development of renal injury, such as interstitial fibrosis after the experimental hydronephrosis. Several recent studies have been demonstrating that one of the initial events taking place in the progressive renal injury process is the mononuclear cell infiltration in the glomeruli and tubulointerstitiuim. In order to evaluate the renal light microscopic findings as well as the renal cortical MCP-1 and TNF-α gene expressions which are modulating inflammatory process and the recruitment of mononuclear cells in many experimental models of renal injury, Sprague-Dawley rats underwent unilateral ureteral obstruction (UUO) and sham operation under the thiopental sodium anesthesia(50 mg/kg intraperitoneal injection). Three and 7 days after surgery, rats were sacrificed. By the competitive RT-PCR, the levels of TNF-α and MCP-1 mRNA in renal cortical tissues were measured. The magnitude of mononuclear cell infiltration and interstitial widening were evaluated by standard point counting method. The level of MCP-1 gene expression was significantly increased in UUO group compared to sham group at 3 and 7 days after surgery(UUO 3 days 8.99 ± 0.45, UUO 7 days 11.2 ± 0.26, sham 3 days 1.00 ± 0.08, sham 7 days 0.94 ± 0.05, p < 0.01, p < 0.01, mean ± SEM, respectively). The level of MCP-1 mRNA at 7 days after surgery was significantly higher than that at 3 days in UUO group. The TNF-α gene expression level of UUO group was also significantly higher than that of sham group at 3 and 7 days after surgery(UUO 3 days 1.73 ± 0.16, UUO 7 days 2.03 ± 0.21, sham 3 days : 1.00 ± 0.06, sham 7 days 1.09 ± 0.03, p < 0.01, p < 0.01, respectively). But there was no significant difference between the levels at 3 and 7 days after surgery in UUO group(p>0.05). On the light microscopic examination, the relative volume of interstitium (RVI) and the total count of infiltrated mononuclear cells(MCC) at 3 and 7 days after surgery in UUO group were also significantly higher than those of sham group(RVI ; UUO 7 days 14.9±1.0%,sham 6.0±0.7%, MCC; UUO 7days 34.0± 1.6, sham 3.7± 0.6, p < 0.01, p < 0.01, respectively). In conclusion, we speculated that the early up-regulation of MCP-1 and TNF-α genes of renal cortical tissue in this experimental hydronephrosis model is closely related to the mononuclear cell infiltration and tubulointerstitial fibrosis.