일차진료에서 흔히 접하는 수분 전해질 문제 ; 이뇨제 사용의 원칙과 실제

전은실 ( Un Sil Jeon ) 대한내과학회 2011 대한내과학회지 Vol.80 No.1

Diuretic drugs are the most commonly used agents to control edema or volume overload. However, the clinical use of diuretics is not confined to edema control. Recently, diuretics have been revisited for the management of various diseases, including hypertension and congestive heart failure. Diuretics are classified mainly by their sites of action in the renal tubules, and have unique characteristics and adverse effects according to their mechanisms of action. To use diuretics adequately, it is very important to understand their characteristics. (Korean J Med 2011;80:8-14)

신장에서 V2 - 수용체를 통한 옥시토신의 aquaporin - 2 발현 조절

전은실(Un Sil Jeon),나기영(Ki Young Na),오윤규(Yoon Kyu Oh),한진석(Jin Suk Han),이정상(Jung Sang Lee),주권욱(Kwon Wook Joo),김진(Jin Kim),김근호(Gheun Ho Kim) 대한내과학회 2002 대한내과학회지 Vol.62 No.3

N/A Background: Oxytocin is a nonapeptide hormone secreted from posterior pituitary gland and has a very similar structure to vasopressin. The aquaporin-2 (AQP2) water channel is predominantly expressed in the kidney and plays a key role in regulation of water permeability of mammalian collecting duct, exerted by both short-term and long-term vasopressin action. We speculated that oxytocin may be involved in some part of vasopressin-independent urinary concentrating mechanism by regulating AQP2 trafficking in the kidney. Methods: This study was undertaken to investigate whether and how the acute stimulation of oxytocin induces changes in AQP2 localization in the kidney. Immunohistochemistry and semiquantitative immunoblotting of AQP2 were carried out from Sprague-Dawley rat kidneys after a single intraperitoneal injection of oxytocin with or without pretreatment of a vasopressin-2 receptor (V2R) antagonist. Results: Urinary cAMP excretion was increased by oxytocin administration. Immuno- histochemistry of inner medullary collecting duct (IMCD) revealed that AQP2 was shifted from diffuse cytoplasmic localization in controls to the apical and basolateral membrane domains in oxytocin-treated rats. This pattern of AQP2 redistribution was noted in connecting tubule, cortical collecting duct and outer medullary collecting duct as in IMCD, although the tendency to basolateral localization was somewhat less. Semiquantitative immunoblotting of membrane fractions of whole kidney homogenates was also used t o assess redistribution of AQP2. The band density ratio of theplasma membrane-rich fraction over cyoplasmic vesicle- rich fraction was higher in oxytocin- treated rat s than in controls (3.64 ±0.60 vs. 1.09 ±0.14, p<0.05>. Regarding the receptor pathway of oxytocin action in the kidney, we found that pretreatment with a V2 R ant antagonist (OPC- 31260) blocked redistribution of AQP2 which was induced by oxytocin. Conclusion: In conclusion, oxytocin induces a V2 R- mediated redistribution of AQP2- containing cytoplasmic vesicles t o both apical and basolateral plasma membrane domains in r at kidney. Oxytocin may be one of the facts or that accounts for vasopressin - independent AQP2 t argeting in the kidney.(Korean J Med 62:268-277, 2002)

외래환자 대상의 금연 프로그램 개발과 효능 평가

김장락(Jang Rak Kim),이옥재(Ok Jae Lee),전은실(Un Sil Jeon),조중현(Joong Hyeon Cho),홍대용(Dae Yong Hong) 대한보건협회 2001 대한보건연구 Vol.27 No.1

N/A N/A

만성신부전에서 염류코르티코이드 투여가 포타시움 평형과 요 암모늄 배설에 미치는 효과

한진석(Jin Suk Han),이정상(Jung Sang Lee),김강석(Kang Seock Kim),허우성(Woo Seong Huh),전은실(Un Sil Jeon),이서진(Seo Jin Lee),주권욱(Kwon Wook Joo),김성권(Suhnggwon Kim),진호준(Ho Jun Chin),조윤숙(Yun Suk Cho) 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.2

N/A Mineralocorticoids influences on acid-base homeo-stasis by the regulation of urine acidification. But its mechanism of acion is not well known in human. This study compared the acid-base status and the indices of urine acidification before and after mineralocorticoid administration in human, and analyzed the effect of mineralocorticoids on human acid-base homeostasis. We administered 9a-fludrocortisone in 6 chronic renal failure patients and 6 normal controls 0.5mg daily for 7 days. The results were as following ' 1) After administration of 9a-fludrocortisone in patients group, serum aldosterone level changed from 120.2±71.0pg/mL to 44.8±32.2pg/mL(mean±SD, p< 0.05). Serum HCO- level was not changed. Urine ammonium excretion was incresed from 24.6±12.3 mmol/day to 43.7±19.0(p<0.05), but there were no change in urine pH and urine anion gap, Serum potassium level decreased from 5.5±0.7mBq/L to 4.1±0.5mEq/L(p<0.05), and TTKG increased from 3.9 to 8.9(p<0.05). 2) After administration of 9a-fludrocortisone in control group, serum aldosterone level changed from 99.7±44.5pg/mL to 25.1±3 mL(p<0.05). Serum HCO- level was not changed. Urine ammonium ex-cretion was incresed from 44.3±21.6mmoVday to 76.3±19.6(p<0.05), but there were no change in urine pH and urine anion gap. Serum potassium level decreased from 4.8±0.5mEq/L to 3.9±0.2mHq/L(p< 0.05), but there was no change in TTKG. 3) No patient or control showed any discomfort after 9-fludrocortisoneadministration, and there was no elevation in diastolic blood pressure, increase in body weight, electrolyte abnormality. In summary, after 9α-fludrocortisane administration, urinary ammonium excretion increased in both patients and control group, and this phenomenon occured with correction of hyperkalemia without urine pH change. This result implies urinary ammonium excretion increase by mineralocorticoid. In human increase in renal distal acidification by mineralocorticoid is due to increase in renal ammo- niagenesis rather than stimulation on proton excretion.

Gitelman 증후군 환자에서 면역조직화학법으로 확인한 원위세관 sodium-chloride cotransporter (NCCT)의 결손

장혜련 ( Hye Ryoun Jang ),허남주 ( Nam Ju Heo ),손민정 ( Min Jung Son ),이재욱 ( Jay Wook Lee ),이정환 ( Jeong Hwan Lee ),전은실 ( Un Sil Jeon ),신성준 ( Sung Jun Shin ),나기영 ( Ki Young Na ),주권욱 ( Kwon Wook Joo ),이정상 ( Jun 대한내과학회 2005 대한내과학회지 Vol.69 No.6

목적 : Gitelman 증후군은 저포타시움혈증, 대사성 알칼리증, 고레닌혈증, 고알도스테론혈증, 요 중 칼슘 배설의 저하 및 저마그네슘혈증을 특징으로 하는 유전성 질환이다. 이는 원위세관 sodium-chloride cotransporter (NCCT)의 유전자 돌연변이에 의하여 발생하는 것으로 알려져 있으나 사람의 신조직에서 NCCT 결손이 증명된 바는 없었다. 방법 : 저자들은 임상적으로 Gitelman 증후군이 의심되는 환자에서 이뇨제를 이용한 신청소율 검사와 유전자 검사를 시행하였고, 이를 통하여 감별진단한 Gitelman 증후군 환자의 신조직에서 인간 NCCT에 대한 토끼 다클론 항체를 이용한 면역조직화학법을 시행하였다. 신세포암으로 신적출술을 시행 받은 환자의 정상 신조직과 전해질 이상이 없었던 사구체신염 환자의 신조직을 각각 정상 대조군과 질환 대조군으로 하였다. 결과 : 대상 환자는 저포타시움혈증과 대사성 알칼리증, 저마그네슘혈증 및 요 중 칼슘 배설의 저하를 보였다. Bartter 증후군과 감별을 위하여 furosemide 및 hydrochlorothiazide를 이용한 신청소율 검사를 시행하였다. 수분 부하를 시행한 기저치(86.1%)에 비해서 furosemide를 투여한 후 distal fractional chloride reabsorption이 감소하였으나(9.7%) hydrochlorothiazide 투여 후에는 변화가 없었다(81.4%). 유전자 검사 결과 SLC12A3 유전자의 돌연변이(S967F)가 발견되었다. 신조직에서 면역조직화학법을 시행한 결과 정상 및 질환 대조군에서는 원위세관 세포의 내강 막 쪽에 NCCT가 뚜렷이 염색되었으나, Gitelman 증후군에서는 원위세관 세포의 NCCT에 대한 면역 반응성이 관찰되지 않았다. 반면에 Na/K-ATPase, Na-K-2Cl cotransporter, calbindin-D28K는 대조군과 대상 환자의 신조직에서 모두 관찰되었다. 결론 : 기능적 검사로 진단된 Gitelman 증후군 환자의 신조직에서 NCCT의 결함을 면역조직화학법으로 확인하였다. Background : Gitelman`s syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. It is known to be caused by a mutation of SLC12A3 gene coding the sodium-chloride cotransporter (NCCT) in the distal tubule. The defect of NCCT in human renal tissues has not been investigated, and we tested whether the defect of NCCT can be detected in renal tissue of a patient with Gitelman`s syndrome by using immunohistochemistry. Methods : In an adult patient with Gitelman`s syndrome, blood and urine samples were collected for measurement of biochemical parameters. Renal clearance study and gene analysis were performed. Immunohistochemistry was performed on the renal tissue of the patient using a rabbit polyclonal antibody directed against a synthetic peptide corresponding to a portion in the amino terminal tail for human NCCT. Normal human renal tissues from surgical nephrectomy due to renal cell carcinoma and renal biopsy tissues from patients with glomerulonephritis but without any electrolyte disturbance were used as controls. Results : The patient had hypokalemic metabolic alkalosis, hypocalciuria and hypomagnesemia. Renal clearance study revealed a decrease in distal fractional chloride reabsorption after the administration of furosemide. SLC12A3 gene mutation (S967F) was found by direct sequencing method. Immunohistochemistry showed the absence of NCCT staining in the renal tissue of the patient. On the other hand, the immunostaining of other transporters was all positive in renal tissues from both Gitelman`s syndrome patients and controls. Conclusions : We report the absence of intact NCCT in the renal tissue of a Gitelman`s syndrome patient.(Korean J Med 69:642-650, 2005)

Oxytocin에 의한 내수질집합관의 cAMP 생성 및 요배설의 변화

한진석(Jin Suk Han),이정상(Jung Sang Lee),김강석(Kang Seock Kim),허우성(Woo Seong Huh),김연수(Yon Su Kim),전은실(Un Sil Jeon),주권욱(Kwon Wook Joo),안규리(Curie Ahn),김성권(Suhnggwon Kim),이중건(Jung Geon Lee),나기영(Ki Young Na),정우경 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.1

N/A Oxytocin, like vasopressin, has been known to act in the IMCD by the activation of adenylyl cyclase through V2 receptor, but the exact mechanism of its action remains to be elucidated. To prove whether oxytocin is involved in the activation of adenylyl cyclase in the renal collecting duct, we measured the cAMP production and urinary cAMP excretion rate. After single IMCD segments of Sprague-Dawley rats were microdissected and treated with different con- centrations of vasopressin(10pM, 10nM) and oxytocin (10pM, 10nM), cAMP production was measured. Urinary cAMP excretion rate was measured after dehydration and intraperitoneal injection of vasopressin and oxytocin. The results are as follows. 1) cAMP production in single IMCD was significantly increased in vasopressin group(10pM: 48,9±4.7(mean±SE), 10nM:94.6±5.3fmol/mm) and oxy-tocin group(10pM: 11.3±2.9, 10nM: 65.7±6.1fmol/mm) compared with that in the control(3.2±0.2fmol/ mm). 2) Urine volume was significantly decreased in dehydration group(40±7μl/hour) and vasopressin group(420±120μl/hour), but urine volume of oxytocin group(1,480±230μl/hour) was not different from that of control(1,550±120μl/hour). Urine osmolality was significantly increased in all experimental groups(control: 737.0±132.6, dehydration group : 2,463.9± 412.5, vasopressin group : 1,702±412.5, oxytocin group 1,293.4±117.9mOsm/kg). Urinary cAMP excretion rate was significantly increased in dehydration group(4,149.5±1,072.3pmol/hour) and oxytocin group(4,843.3±2,341.8pmol/hour), but not in vasopressin group(1,358.1±690.2pmol/hour), compared with that in control(49±10.7pmoVhour). These results suggest that oxytacin has anti-diuretic effect by the activation of adenylyl cyclase through V2 receptor.

규폐증 환자에게 발생한 막성 신병중 1 예

하혜정(Hye Jung Ha),김현정(Hyun Jung Kim),김수희(Su Hi Kim),이경원(Geoung Won Lee),김태효(Tae Hyo Kim),양중일(Jung Il Yang),최영미(Young Mi Choi),전은실(Un Sil Jeon),장세호(Se Ho Chang) 대한신장학회 2001 Kidney Research and Clinical Practice Vol.20 No.3

N/A

정상인에서 옥시토신의 항이뇨 작용

주권욱,전은실,오윤규,김근호,한진석,김성권,이정상 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.2

배 경 : 옥시토신은 바소프레신과 매우 유사한 구조의 호르몬으로서, 과거부터 항이뇨 효과가 있을 것으로 생각하였으나, 최근에야 체외실험을 통하여 옥시토신의 항이뇨 작용이 증명되었다. 인체에서도 옥시토신이 항이뇨 호르몬으로 작용할 가능성이 있지만 아직 분명하지 않다. 저자들은 정상인에게 옥시토신 또는 desmopressin(dDAVP)을 투여하여 인체에서 옥시토신의 항이뇨 효과를 직접적으로 검증하고자 하였다. 방 법: 신기능 장애의 증거가 없는 건강한 성인 남자 10명을 대상으로 기저상태와 옥시토신(20 mU/hour로 정주) 또는 dDAVP(2 μg을 피하 주사)를 투여한 후 2시간 동안 수집한 요에서 요량, 요 삼투질농도, 자유수분 청소율 등을 측정하였고, 요 전해질 배설의 변화를 함께 관찰하였다. 결 과 : 혈청 전해질이나 삼투질농도는 옥시토신 또는 dDAVP 투여 후에 기저상태에 비해 유의한 변화가 없었다. 2시간 요량은 기저상태 446±75 mL로부터, dDAVP 투여 후 92±9 mL로 감소하였고(p<0.05), 옥시토신 투여 후에는 289±53 mL로 변화하였다. 요 삼투질농도는 기저상태 223±25.0 mOsm/kg에서, dDAVP 투여 후 936±34 mOsm/kg 및 옥시토신 투여 후427±63 mOsm/kg로 모두 증가하였다(p<0.05). 자유수분 청소율은 기저상태 110±51 mL/2hour로부터, dDAVP 투여 후 -218±28 mL/2 hour, 옥시토신 투여 후 -57±51 mL/2 hour로 각각 감소하였다(p<0.05). 요나트륨분획배설율(FENa)을 포함한 다른 요 전해질 배설의 유의한 변화는 없었다. 결 론 : 옥시토신이 정상 성인 남자에서 요 삼투질농도의 증가 및 자유수분 청소율의 저하를유발함을 확인하였으며, 이는 옥시토신이 인체에서도 항이뇨 작용이 있음을 시사하는 결과이다. 그러나 생리적인 농도에서 옥시토신이 어떤 역할을 할 것인가와 그 작용기전은 앞으로 규명되어야 할 과제이다. Background : The antidiuretic action of oxytocin in human has been controversial. To investigate whether oxytocin directly acts on water balance in human, we evaluated the parameters of urinary concentration in response to administration of oxytocin in ten healthy male volunteers. Methods : Oxytocin was infused intravenously at a rate of 20 mU/hour for 2.5 hours and urine was collected during the last 2 hours of oxytocin infusion. Changes in urine volume, urine osmolality, excretions of urine electrolytes and free water clearance after the administrartion of oxytocin were compared with the baseline data. Results : The changes in the levels of serum electrolytes and osmolality after the administration of oxytocin were not significant compared with the baseline data. The volume of 2 hours' urine were 446±75 mL and 289±53 mL in the basal state and after the administration of oxytocin, respectively. The urine osmolality was increased significantly by the infusion of oxytocin(427±63 mOsm/kg) compared with that in the basal state(223±25 mOsm/kg)(p< 0.05). The free water clearance was 110±51 mL/2 hours in the basal state and decreased significantly to -57±51 mL/2 hours(p<0.05). Conclusion : We conclude that administration of oxytocin to normal men enhances urinary concentration, evidenced by increased urinary osmolality and decreased free water clearance. In human, oxytocin may play an important role in the regulation of renal water excretion as an antidiuretic hormone. (Korean J Nephrol 2002;21(2):251-258)

신기능 장애를 동반하는 고혈압 환자에서 Fosinopril Sodium(Monopril^R)의 강압효과

정윤철,전은실,임춘수,안규리,한진석,김성권,이정상 大韓臨床藥理學會 1998 臨床藥理學會誌 Vol.6 No.1

원위부 신세뇨관성 산증에서 산-염기 운반체의 결손

김혜영,한진석,전은실,진호준,주권욱,나기영,정우경,오지은,김현리,이서진,이중건,김근호,엄재호,궁성수,김진,이정상 대한신장학회 2000 대한신장학회잡지 Vol.19 No.5