Effects of Iron Chelators and Reducing Agents on Iron induced Lipid Peroxidation

Park, Chan-Hyun,Lee, Chung-Soo,Shin, Yong-Kyu,Lee, Kwnag-Soo 중앙대학교 의과대학 의과학연구소 1987 中央醫大誌 Vol.12 No.3

금속이온 가운데 iron은 산소라디칼에 의한 생체 세포내 거대분자의 파괴를 촉매하며 iron의 환원이 지질의 과산화에 주요한 역할을 하는 것으로 알려져 있다. OH·을 생성하는 Haber-Weiss reaction은 iron에 의하여 촉진되며, 생성된 OH·이 지질의 과산화를 초래하는 물질로서 시사되고 있다. Iron에 의한 불포화 지방산의 과산화에는 ferrous-dioxygen복합체 또는 제일 철(혹은 착화 제일 철)의 자가산화 반응중에 산소라디칼이 형성되어 이들이 관여하는것으로 추측하고 있다. 한편 다수의 보고들은 생체내에 존재하는 환원제의 하나로써 ascorbate가 지질의 과산화를 포함한 세포내 거대분자의 손상을 초래하며 또한 금속이온의 독성작용을 항진시킨다고 보고하고 있다. 이와 같이 iron의 산화와 환원이 지질의 과산화에 관여할 가능성에서 볼 때, ascor-bate와 같은 환원제들의 환원력이 갖는 역할은 이들의 독성작용에 기여하는 작용을 밝히는 계기가 될 것이다. 그러므로 본 연구에서는 iron의 산화 또는 환원에 따른 조직 손상의 정도를 여러 환원제와 iron chelator존재하에서 나타나는 현상으로써 측정하였다. 이들 효과는 iron의 산화중에 유리되는 산소라디칼과 microsome의 지질의 과산화를 통하여 관찰하였다. 또한 이온의 산화 및 환원에 미치는 iron chelator와 환원제들의 영향을 관찰하였으며 더 나아가 iron의 산화 및 환원과 이에 따른 지질의 과산화 사이의 관계를 규명하였다. Fe^++은 microsome의 질을 과산화시켰으나 Fe^++은 100uM농도까지 지질의 과산화에 약간의 영향을 나타내었다. 중성의 반응액에서 Fe^++ 은 5분내에 거의 완전히 산화되었으며 이와 동시에 ferricytochrom c가 환원되었다. 이에 반하여 Fe^++은 ferricytochrom c의 환원에 거의 영향을 나타내지 아니 하였다. Fe^++에 의한 microsome지질의 과산화는 O_2의 scavenger인 SOD와 H_2o_2의 scavenger인 catalase 에 의하여 억제되었다. EDTA 또는 DETAPAC은 Fe^++에 의한 microsome 지질의 과산화에 이중효과를 나타내었으며 EDTA 또는 DETAPAC과 iron의 결합이 1:2일때 iron에 의한 지질의 과산화는 증가하였으나, 이러한 비율에서 벗어날 때는 오히려 iron에 의한 지질의 과산화는 억제되었다. ADP 는 Fe^++에 의한 지질의 과산화를 억제하였으나 Fe^++에 의한 지질의 과산화를 촉진시켰다. EDTA또는 ADP 는 Fe^++의 자발적인 산화를 촉진하였으나 DETAPAC은 용량에 따라 억제하였다. 한편 salicylate의 hydroxylation은 EDTA나 DETAPAC 에 대한 Fe^++의 결합비율이 2:1일 때 가장 크게 이루어졌으며 이러한 비율에서 벗어날때 hydroxylation속도는 감소되었다. ADP 또한 salicylate 의 hydroxylation 을 억제하였다. 여러 환원제 가운데 ascorbate는 Fe^+++의 환원과 iron에 의한 지질의 과산화를 가장 강력하게 촉진하였다. Fe^++와 ascorbate의 첨가에 따른 지질의 과산화는 Fe^+++와 ascorbate에 의한 것보다 훨씬 현저하였다. Fe^++또는 Fe^++와 ascorbate 의 상호반응에 의한 ferricytochrom c의 환원은 SOD에 의하여 뚜렷하게 억제되었으나, ascorbate 자체에 의한 ferricytochrom c의 환원은 SOD에 의하여 약간 억제되었다. 한편 cysteine,NADH와 giutathione중에서 cysteine에 의한 ferricytochrom c 의 환원만이 SOD 에 의하여 억제되었다. 이상의 결과로부터 iron의 산화와 환원을 억제 또는 촉진시키는 물질은 지질의 과산화를 억제하거나 촉진 시키므로 iron의 산화 및 환원과 지질의 과산화 사이에는 관계가 있을 것으로 사료되었다. 또한 이러한 반응에서 OH·같은 산소라디칼이 iron의 산화 및 환원에 따른 지질의 과산화를 초래하는 매개물질로서 작용할 가능성이 시사되었다. Iron is a reactive metal ion which is known to catalyze damages of cellular rnacrornolecules causrd by oxygen radicals and its reduction may play a major role in lipid peroxidation. The iron-catalyzed Hater-Weiss reaction to produce OH is catalyzed by iron and OH appear to participate as an initiator of lipid peroxidation. Ferrous(or chelated) ion will also initiate peroxidation of unsaturated fatty acids. This initiation may of cur via abstraction by a ferrous-dioxygen complex or alternatively may involve 0_2, H_2O_2 or other partially reduced oxygen species generated through fur-ther autoxidation reactions of the ferrous che-lates. Many studies have reported toxic effects of ascorbate on various biological materials including lipid and DNA peroxidation. In view of data suggesting that the effect of iron on lipid peroxidation is mediated by its oxidore-duction, reducing actiyity of reducing agents such as ascorbate may be the mechanism through which the toxic action of ascorbate is mediated. In the Present study, the effect of oxidore-ducticn of iron on tissue damages was inves-tigated in the presence of various reducing agents or iron chelators. These effects were studied with respect to generation of oxygen radicals during oxidation or reduction of iron in relation to the lipid peroxidation caused by iron. The effects of reducing agents or iron chelators on redox phenomenon of iron were also observed. Furthermore, the relationship between oxidoreduction of iron and lipid pero-xidation was studied. Lipid peroxidation of microsomes was increased with concentration of Fe^++, but Fe^+++ had little effect. In reaction medium of pH 7.4, Fe^++ was almost compte-tely autoxidized at 5 min after the reaction and during this process superoxide radical was formed. Lipid peroxidation of microsomes by Fe^++ was inhibited by SOD and catalase. EDTA or DETAPAC showed dual effects on lipid peroxidation by Fe^++ When proportion of these chelators to iron was 1:2, lipid peroxidation was enhanced but when this ratio is altered, lipid peroxidation was inhibited. ADP prevented lipid peroxidation by Fe^++ and stimulated that by Fe^+++, EDTA or ADP facilitated autoxidation of Fe^++ whereas DE-TAPAC inhibited. On the other hand, when proportion of EDTA or DEfAPAC to Fe^++ was 1:2, hydroxylation of sodium salicylate was maximum and fell off as this proportion was altered. ADP also prevented hydroxylation of salicylate by Fe^++ Among various reducing agents tested ascorbate had a most potent reducing power and also most remarkably facilitated lipid peroxidation by iron. Lipid peroxidation caused by interaction of Fe^++ and ascorbate was greater than that by interaction of Fe^++ plus ascorbate. Reduction of ferricyto-chrorne c was enhanced by ascorbate in a dose dependent manner, but other reducing agents showed little effect. Reduction of ferricytoch-rorne c by Fe^++ alone or Fe^++ plus ascorbate was signifi cantly inhibited by SOD. However, reduction of ferricytochrorne c by ascorbate alone was slightly inhibited by SOD. From these results obtained, it is suggested that oxidoreduction of iron plays the major role in tissue damages including lipid peroxidation caused by iron dependent reactions and there is the relationship between the oxidoreduction of iron and lipid peroxidation. Also, it appears that oxygen radicals such as OH·plays at least a partial role in initiating lipid peroxidation.

Oualbain과 Verapamil이 심근칼슘저장고에 미치는 영향

김병국,엄대용,이상돈 중앙대학교 의과대학 의과학연구소 1981 中央醫大誌 Vol.6 No.1

The control isometric contraction of rabbit papillary muscle preparations were recorded by the stimulation 'frequency of 1 Hz. and priming stimulation were applied to activate the intracellular calcium by the stimulation frequency of 5 Hz. for 5 seconds. After the resting period, the amplitudes of contraction, were compared with that of control and the ratios were plotted with respect to time in a semi-log paper. The experiments were performed in a control Tyrode solution, high calcium solution, ouabain solution and verapamil solution. The following results were obtained; 1. la a normal Tyrode solution, the fast compartment which is responsible for the fast decay of intracellular calcium within 3-5 seconds after the priming stimuli and the slow compartment, slowly decayed one after 5 seconds, could be identified. 2. Although the fast components showed no significant differences between those in a normal Tyrode solution and in a high calcium (4mM) solution, the slow components showed a rather increasing tendency during the normal initial decay period up to 20 seconds and later on a decreasing tendency. 3. In a ouabain, 2.4 -4.8×10^-7M, treated preparation the amplitude of contraction during the control period was increased up to 1.5 times compared with that in a normal Tyrode solution and the characteristics of calcium pools were qualitatively similar to those in high calcium solution. 4. In a verapamil, 1.1×10^-6M, containing solution the amplitude of control contraction were reduced to two thirds compared with that in normal Tyrode solution and the fast component were markedly influenced, reversed its slope to increase slowly up to 20 seconds and then decayed. 5. The characteristics of intracellular calcium pools la a preparation of verapamil and high calcium conditions at the same time showed rather similar patterns with those in verapamil alone treated preparation. The above results showed that the intracelluar calcium pools were composed of two components which were fast and slow decaying ones, and that ouabain and verapamil would alter the characteristics of the calcium pools to increase and decrease the intracellular calcium respectively.

인천지역산 굴 및 조개류의 Enteroviruses 오염에 관한 연구

양용태,이철성,최철순,정상인 중앙대학교 의과대학 의과학연구소 1984 中央醫大誌 Vol.9 No.1

In some countries, it has been firmly established that shellfish could play a significant role as reservoir of human enteric viruses. Several outbreaks of infectious hepatitis were traced to the ingestion of contaminated oysters and hard clams. Furthermore, numerous studies demonstrated clearly that enteroviruses of all four subgroups were present in contaminated streams, in sewage, and in effluent from the sewage treatment plants. In Korea, intensive studies have been made on the contamination of fishes and shellfish with V.parahaemolyticus. However, no effort has been made to isolate and to define the nature of enteroviruses contaminating the shellfish. The purpose of this study were 1) to examine the susceptibility and applicability of HeLa and Vero cell lines for the isolation of enteroviral agents from shellfish samples, 2) to evaluate the efficiency of shellfish processing procedure for the virus isolation from shellfish, and 3) to isolate enteroviral agents from a variety of shellfish (Meretrix lusoria, Tapes philippinarum, Tapes variegata, Saxidomus purpuratus, Tegillarca granosa, Scpharca broughtonii) in Vero cells through blind passages and plaque formation assay. The results are summarized as follows: 1. Of 19 shellfish samples tested, only 3 produced definite CPE in Vero cells through blind passages up to the 2nd passage. However, plaque assays in Vero cells with ultracentrifugation sediments, and 1st and 2nd passage supernatants in Vero cells were all negative. 2. This study demonstrated that the culture of Vero cell line is suitable for the isolation of poliovirus from shellfish samples. 3. Recovery experiment of poliovirus added to the shellfish homogenate showed that shellfish processing procedure for virus isolation was applicable for the isolation of poliovirus but the virus recovery rate was significantly low.

한국 소아 청소년의 비만과 대사이상 지표들에 관한 연구

이지영,최병선,박정덕,최응상,엄상용,김헌,하미나,권호장,임지애,김유미,홍영습,윤용운,손석준,채수안,임인석,유병훈,윤신원 중앙대학교 의과대학 의과학연구소 2013 中央醫大誌 Vol.38 No.4

Purpose: Obesity and metabolic syndrome in the pediatric population have become major health concerns; however, Korean nationwide data are limited. The lack of a clear definition of child obesity is a problem worldwide. We performed a pilot study of Korean school-aged children and adolescents to determine the prevalence of obesity according to various 4 parameters and to identify associations with socioeconomic parameters and metabolic risk factors. Methods: Between January 2010 and March 2011, 1,110 students from 11 Korean provinces ranging in age from 6 to 18 years, including 574 boys and 536 girls, were enrolled. Weight, height, and waist circumference were measured; fasting blood samples were collected; and socioeconomic factors were assessed. Results: The prevalences of obesity in boys and girls according to body mass index (BMI) were 5.7% and 2.1%, and according to obesity index were 12.7% and 11.4%, respectively. The male to female obesity ratio was higher according to waist circumference (57.9% : 36.1%) and waist circumference-to-height ratio (WHTR) (19.0% : 24.8%). The best obesity index was WHTR, and the proportion of participants with triglyceride-to-HDL cholesterol ratio ≥3 was 6.8%. The prevalence of hypertriglyceridemic waist phenotype was 11.8%. Overweight and obesity was higher in rural than in urban areas. Conclusion: The optimal cutoff for the definition of obesity in school-aged students has not been determined. Therefore, the physical characteristics of children including waist circumference and lipid profiles should be assessed according to age.

Isolated Infective Endocarditis on Pulmonary Valve Caused by Aggregatibacter aphrophilus in Patient with Ventricular Septal Defect

Hae Lim Baek,Yong Kyun Cho,Mi-Seung Shin,Song Mi Moon,Suyoung Kim,Kang-lock Lee,Young Rock Jang,Woo Suk Choi 중앙대학교 의과대학 의과학연구소 2013 中央醫大誌 Vol.38 No.4

Infective endocarditis caused by Aggregatibacter aphrophilus, which is one of the members of HACEK group, is rare and mitral valve is known as a prominently affected site in most cases. We report a case of isolated pulmonary valve infective endocarditis caused by A. aphrophilus in a patient with congenital heart disease. Twenty five-year-old woman with ventricular septal defect visited our hospital complaining fever lasting 3 weeks. Not any vegetation was observed at transthoracic echocardiography due to limited echo window. However, transesophageal echocardiography showed a small vegetation attached to the pulmonary valve. The patient was successfully treated with ceftriaxone for 4 weeks.

비외상성 횡문근 융해증으로 인한 급성신부전 1예

박윤수,한민지,김채림,김진수,김재웅,심희준,신정호,김수현,유석희 중앙대학교 의과대학 의과학연구소 2013 中央醫大誌 Vol.38 No.3

A 45-year-old woman without a previous history of renal disease reported abdominal pain, diarrhea, oliguria and whole body edema. She was taking long term personal training, diet supplements and NSAIDs. Adding to these conditions, major symptom can be estimated a non-traumatic cause of drug induced acute renal failure, but a rise in the indices of muscle damage in laboratory test was minimal. Rhabdomyolysis is a non-traumatic condition leading to hemodialysis. Rhabdomyolysis is a clinic syndrome occurring from the influx of contents of muscles cells into the blood due to musculoskeletal damages, most of the causes of which have recently included non-traumatic muscle damages as well as serious traumas. Without proper early treatments, serious complications are expected, and early diagnostics and treatments are important for its prevention.

수술 후 보조적 항암화학치료을 시행한 원발성 폐암육종 1예

조형준;강주현;김정호;사영경;윤형규;송정섭;박찬권 중앙대학교 의과대학 의과학연구소 2012 中央醫大誌 Vol.37 No.1/2

Pulmonary carcinosarcoma (sarcomatoid carcinoma of the lung) is a rare pulmonary malignancy which is defined as having an admixture of both carcinomatous and sarcomatous components. Pulmonary carcinosarcoma occurs most frequently in males between 50 and 60 years of age, who have smoking history. Here, we report a case of pulmonary carcinosarcoma in a 53-year-old man who presented with dyspnea. A left lower lobectomy was performed. The postoperative definite diagnosis was carcinosarcoma of the lung. The patient subsequently received adjuvant chemotherapy with cisplatin and vinorelbine.

Outcomes of Free-Tension Transobturator Tape (TOT) Surgery under Local Anesthesia versus General Anesthesia for Female Stress Incontinent Treatment

응웬하이박 외 중앙대학교 의과대학 의과학연구소 2011 中央醫大誌 Vol.36 No.3/4

We evaluate our experience with Transobturator Tape (TOT) surgery under local and general anesthesia for treating female stress incontinence. Totally 31 women with genuine urinary incontinent were selected in this study. They were scheduled for TOT surgery under local anesthesia or general anesthesia. The study protocol involved recording of preoperative and perioperative details and postoperative evaluation. Fifteen patients were included in local group and sixteen remainders in the general group. 100% of stress urinary incontinent symptom was cured. The cure rate of urge symptom was 80% vs. 50% for local group vs. general group, respectively, at both short-term and long-term follow-up. There was no significant difference in mean operating room and surgical time. But a statistically significant difference in mean of recovery room time, hospital stays and hospital cost was recorded (p <0.005). We concluded that TOT insertion is a best indication for correcting urinary stress incontinence in women. It can be performed effectively under both local and general anesthesia. Local anesthesia with sedation has advantage only in regarding to recovery time and total hospital cost, but much disadvantage in term of early and late postoperative complications.

대장내시경검사로 진단된 급성막창자꼬리염 2예

이상욱 외 중앙대학교 의과대학 의과학연구소 2011 中央醫大誌 Vol.36 No.1/2

We diagnosed 2 cases of acute appendicitis on the basis of the colonoscopic findings of mucosal edema, hyperemia. In the first case, an abdominal CT scan showed an inflamed mass in the right lower quadrant that involved the terminal ileum and sigmoid colon after the colonoscopy. The patient received conservative therapy to reduce the inflammation, and following this appendectomy was performed. In the second case, the patient showed no typical acute appendicitis symptoms before endoscopy, although the incidental findings of acute appendicitis were noted during colonoscopy. Immediate appendectomy was performed, and the pathologic findings revealed acute suppurative appendicitis.

혈액투석 환자에서 요독가려움증의 유병율

신정호 외 중앙대학교 의과대학 의과학연구소 2011 中央醫大誌 Vol.36 No.1/2

Introduction: Uremic pruritus is a common disabling symptom and is associated with quality of life in patients with maintenance hemodialysis. The pathogenesis of uremic pruritus remains uncertain. In this study, we evaluated the prevalence and related factors of uremic pruritus. Materials and Methods: Ninety-three patients who were treated with maintenance hemodialysis for more than 3 months in our center were included and they were researched for clinical findings and possible related factors such as age, sex, dialysis duration, underlying disease and dialysis membrane. We also investigated about antihypertensive drugs, erythropoietin use, laboratory data and dialysis dose. Results: There were fourty-five patients who experienced with pruritus and fourty-eight patients who without pruritus. There were no significant difference between patients with pruritus and without pruritus about sex, dialysis duration, underlying disease, dialysis membrane, erythropoietin use, antihypertensive drugs, laboratory data and dialysis dose. The mean age was different between two groups; the mean age of patients with pruritus was 62.4±12.2 years and that without pruritus was 56.6±12.4 years (p =0.026). Conclusion: The prevalence of pruritus in our study was fourty eight percent, and older age was associated with increased incidence of uremic pruritus.