• Childhood Kidney Diseases
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• 제24권1호
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• pp.42-46
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• 2020

Disturbances in water and salt balances are relatively common in children after brain tumor surgery. However, the coexistence of different diseases of water and sodium homeostasis is challenging to diagnose and treat. The coexistence of combined central diabetes insipidus (CDI) and cerebral salt wasting syndrome (CSWS) is rare and may impede accurate diagnosis. Herein, we report the case of an 18-year-old girl who underwent surgery for a germinoma and who presented prolonged coexistence of CDI and CSWS. The patient was diagnosed with panhypopituitarism with CDI at presentation and was treated with hydrocortisone, levothyroxine, and desmopressin. Postoperatively, she developed polyuria of more than 3L/day, with a maximum daily urine output of 7.2 L/day. Her serum sodium level decreased from 148 to 131 mEq/L. Polyuria was treated with desmopressin at incremental doses, and hyponatremia was managed with fluid replacement. At 2 months after surgery, she presented with hyponatremia-induced seizure. Polyuria and hyponatremia combined with natriuresis indicated CSWS. Treatment with fludrocortisone were initiated; then, her electrolyte level gradually normalized. CSWS is self-limiting and generally resolves within 2 weeks. However, the patient in this study still required treatment with vasopressin and fludrocortisone at 16-months after surgery. Hyponatremia in a patient with CDI may be erroneously interpreted as inadequate CDI control or syndrome of inappropriate antidiuretic hormone secretion, leading to inappropriate treatment. The identification of the potential combination of CDI and CSWS is important for early diagnosis and treatment.

• 한국산학기술학회논문지
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• 제10권11호
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• pp.3473-3479
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• 2009

비펩타이드성 안지오텐신 수용체 길항제로 새롭게 개발된 KR-31081에 대한 생체 내 활성을 세가지 동물모델에서 검증하였다. 척수장애 동물모델에서 KR-31081은 로사탄보다 40배 이상의 경쟁적인 혈압강하 효과를 나타내었으며, 신성고혈압쥐 모델에서 KR-31081은 로사탄보다 10배 가량의 지속형 효과를 나타내었다. 또한 개실험에서 구강 투여한 KR-31081은 로사탄보다 20배 이상의 지속적인 혈압강하 효과를 나타내었다. 실험에 사용된 동물 모델 시스템에서 다른 혈관조절물질들과 상호작용을 하지 않는 것으로 나타난 KR-31081은 향후 고혈압 및 혈관질환에 대한 연구 및 진단에 활용될 수 있을 것이라고 판단된다.

• The Korean Journal of Physiology
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• 제20권1호
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• pp.89-102
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• 1986

It has long been suggested that the change of renin-angiotensin system is responsible for the increased arterial blood pressure in the experimental hypertension. But the exact nature of the cause and maintenance of early and late Phase of renal hypertension is still controversial. Increased renin-angiotensin system has been suggested. To clarify the altered renin-angiotensin system in the early phase of two kidney one clip Goldblatt hypertension(2K1C GH), experiments were carried out in the rats of 3,7, and 14 days of 2K1C GH rats, sham-operated, and control rats. Responses of the plasma renin activity to the intravenous infusion of L-isoproterenol were dose-dependent. Responses of the plasma renin activity to the intravenous L-isoproterenol in 2K1C GH rats were not different from sham-operated control rats. Hypotensive responses of the 2K1C GH rats were not different from sham-operated rats. Suppression by intravenous infusion of angiotensin II of plasma renin activity showed a dose-dependent manner. Suppression by angiotensin ll of plasma renin activity was attenuated or abolished in the early phase of 2K1C GH rats. Intravenous infusion of arginine vasopressin(AVP) showed a dose-dependent suppression of plasma renin activity, Attenuated responses by AVP of plasma renin activity were noticed in the early phase of 2K1C GH rats. These results suggest that the altered renin-angiotensin system in the early phase of the two kidney one clip Goldblatt hypertension may be caused by failure of the short loop negative feedback control mechanism.

• Journal of Yeungnam Medical Science
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• 제22권2호
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• pp.259-265
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• 2005

Central diabetes insipidus (DI) is a syndrome characterized by thirst, polydipsia and polyuria. Langerhans cell histiocytosis is one of the etiologies of DI. Recently we experienced a central DI associated with Langerhans cell histiocytosis. The 44 years old female patient complained right hip pain, polydipsia and polyuria. We carried out water deprivation test. After vasopressin injection, urine osmotic pressure was increased from 109 mOsmol/kg to 327 mOsmol/kg (300%). Brain MRI showed a thickened pituitary stalk and air bubble like lesions sized with 5cm, 7cm was shown on fifth L-spine and right hip bone at hip bone CT. CT guided biopsy revealed abnormal histiocytes proliferation and abundant lymphocytes. The final diagnosis was central DI associated with systemic Langerhans cell histiocytosis invading hip bone, L-spine and pituitary stalk. Desmopressin and etoposide chemotherapy were performed to the patient.

• 병원약사회지
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• 제35권4호
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• pp.430-440
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• 2018

Background : Hyponatremia is the most common electrolyte disturbance in hospitalized patients and has been associated with increased morbidity and mortality. Tolvaptan, a vasopressin receptor antagonist, is increasingly used for the treatment of euvolemic and hypervolemic hyponatremia. The aim of this study was to evaluate the effectiveness and safety of tolvaptan for the management of hyponatremia. Methods : This study was a retrospective evaluation of 106 patients who received at least one dose of tolvaptan for hyponatremia at a single tertiary academic hospital between January 2014 and June 2015. The primary endpoint was the change in serum sodium concentration after tolvaptan administration within 24 hours, with secondary endpoints of overcorrection and adverse effects. Results : The mean initial dose of tolvaptan was $20.2{\pm}7.2mg$ and the median duration of treatment was 15 days (range, 1-261 days). The maximal changes in sodium levels at 24 and 48 hours were $8.2{\pm}4.7mmol/L$ and $10.5{\pm}15.3mmol/L$, respectively. Of 99 patients in whom sodium concentrations were followed up, sodium overcorrection was observed in 26 (26.3%) patients, which was associated with concomitant use of an enzyme inhibitor (odds ratio [OR] = 4.80, 95% Cl: 1.27-18.15). However, sex, body mass index (BMI), serum albumin, a daily dose of tolvaptan, and concomitant use of hypertonic saline did not show any significant difference in overcorrection. The most commonly reported adverse effects were mild and related to aquaresis, such as polyuria, thirst, and constipation. However, severe adverse effects such as hyperkalemia, hypotension, and one death related to osmotic demyelination were also reported. Conclusions : Tolvaptan is effective for treating hyponatremia. Nevertheless, the drug should be used cautiously due to serious adverse effects related to sodium overcorrection.

• The Korean Journal of Physiology and Pharmacology
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• 제26권4호
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• pp.255-262
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• 2022

Oxytocin is a neuropeptide produced primarily in the hypothalamus and plays an important role in the regulation of mammalian birth and lactation. It has been shown that oxytocin has important cardiovascular protective effects. Here we investigated the effects of oxytocin on vascular reactivity and underlying the mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and in rat aorta ex vivo. Oxytocin increased phospho-eNOS (Ser 1177) and phospho-Akt (Ser 473) expression in HUVECs in vitro and the aorta of rat ex vivo. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), inhibited oxytocin-induced Akt and eNOS phosphorylation. In the rat aortic rings, oxytocin induced a biphasic vascular reactivity: oxytocin at low dose (10^-9-10^-8 M) initiated a vasorelaxation followed by a vasoconstriction at high dose (10^-7 M). L-NAME (a nitric oxide synthase inhibitor), endothelium removal or wortmannin abolished oxytocin-induced vasorelaxation, and slightly enhanced oxytocin-induced vasoconstriction. Atosiban, an oxytocin/vasopressin 1a receptor inhibitor, totally blocked oxytocin-induced relaxation and vasoconstriction. PD98059 (ERK1/2 inhibitor) partially inhibited oxytocin-induced vasoconstriction. Oxytocin also increased aortic phospho-ERK1/2 expression, which was reduced by either atosiban or PD98059, suggesting that oxytocin-induced vasoconstriction was partially mediated by oxytocin/V1aR activation of ERK1/2. The present study demonstrates that oxytocin can activate different signaling pathways to cause vasorelaxation or vasoconstriction. Oxytocin stimulation of PI3K/eNOS-derived nitric oxide may participate in maintenance of cardiovascular homeostasis, and different vascular reactivities to low or high dose of oxytocin suggest that oxytocin may have different regulatory effects on vascular tone under physiological or pathophysiological conditions.

• 한국동물위생학회지
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• 제45권2호
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• pp.139-143
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• 2022

A 10-year-old, spayed female miniature schnauzer was referred to the Veterinary Medical Teaching Hospital of Chungnam National University due to evaluation of sudden polyuria (PU) and, polydipsia (PD) (540 mL/kg/day) with severe anemia and weight loss. Blood examination results were normal except for severe anemia (hematocrit, [HCT]: 11.8%). Urinalysis revealed a urine specific gravity (USG) of 1.003, whereas urine sediment was not specific. Urine osmolality was 90 mOsm (reference range: 800~2500 mOsm), and plasma osmolality was 303 mOsm. No specific lesions were found using diagnostic imaging including radiography, ultrasonography and magnetic resonance imaging (MRI). The serum cortisol level was normal in cosyntropin stimulation test. Plasma arginine vasopressin (AVP) concentration was <0.4 pg/mL (reference range: 3.49~5.45 pg/mL). Blood transfusion was initiated in addition to an oral prescription of desmopressin acetate (DDAVP, 0.1 mg/head) thrice a day for one week. The patient was rechecked for clinical signs, urine osmolality, and USG; the clinical signs of PU/PD were resolved, urine osmolality increased to 1106 mOsm, and, USG increased to 1.021. Considering the improved clinical signs, and increased urine osmolality, and USG after DDAVP treatment, the dog was diagnosed with central diabetes insipidus. USG and urine osmolality increased to >1.030 and 2200 mOsm, respectively. Anemia also gradually improved and HCT increased to >37%. DDAVP was tapered to 0.1 mg/head twice a day and all clinical signs in the patient have completely resolved.

• Clinical and Experimental Reproductive Medicine
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• 제36권4호
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• pp.275-281
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• 2009

목 적: 본 연구는 반복적으로 체외수정시술/난자세포질내 정자주입술을 실패했던 환자에서 배아 이식시 옥시토신 길항제의 투여가 임신율 및 착상율에 미치는 영향을 알아보고자 하였다. 연구방법: 2회 이상의 체외수정시술/난자세포질내 정자주입술을 실패했던 40명의 환자들을 대상으로 전향적 무작위 연구를 진행하였다. 과배란유도 방법으로 생식샘자극호르몬분비호르몬 길항제 다회투여법이 사용되었다. 실험군에서는 옥시토신 길항제로 atosiban (vasopressin $V_{1A}$/oxytocin antagonist)을 배아 이식 한 시간 전에 atosiban 6.25 mg을 일회 정주한 뒤, 18 mg/hour의 속도로 지속적 정맥 주입하였다. 배아 이식이 끝난 뒤 atosiban을 6 mg/hour로 감속하여 2시간 동안 추가로 정맥 주입하였다. 실험군과 대조군간의 체외수정시술 결과를 비교 분석하였다. 결 과: 실험군과 대조군간의 평균 나이, 불임 기간 및 체질량 지수와 기저 혈중 난포자극호르몬 및 에스트라디올 농도, 기저 난포강 난포의 수에 통계적으로 유의한 차이는 없었다. 또한 투여된 재조합 인간 난포자극호르몬 (rhFSH)의 총 용량과 투여 기간, 발달된 난포의 개수 및 자궁내막의 두께 역시 통계학적 유의한 차이를 보이지 않았다. 수집된 난자 및 성숙 난자의 수와 수정된 난자와 1등급 혹은 2등급의 배아 및 이식된 배아의 수에도 두 군간의 통계학적으로 유의한 차이를 보이지 않았다. 착상율을 비교하였을 때 실험군은 16.9% (11/65), 대조군은 6.0% (4/67)로 나타났고, p=0.047로 두군 간에 통계학적으로 유의한 차이를 보였다. 임상적 임신율의 경우 실험군은 40.0%로 대조군의 20.0%에 비해 높게 나타나으나 통계학적 유의성엔 도달하지 못하였다. 또한 자궁외 임신 및 유산율에 있어서는 두 군 간에 유의한 차이를 보이지 않았다. 결 론: 체외수정시술/난자세포질내 정자주입술을 시행 받는 환자들에서 배아 이식 동안 옥시토신 길항제를 투여하는 것은 자궁의 수축을 감소시켜 착상율을 증가시킬 수 있을 것으로 생각된다.

• Childhood Kidney Diseases
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• 제4권1호
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• pp.69-76
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• 2000

목 적 : 일차성 야뇨증의 병인론은 유전적 요인 외에 수면 요인, 야간 Arginine Vasopressin(AVP)분비 장애, 기능적 방광 미숙 등 주로 배뇨 반사의 성숙 지연이 논의되고 있으나 위험 요인에 대한 연구는 적었다. 이에 저자들은 소변을 충분히 가릴 나이인 5세 이후까지 야뇨증을 지속시킬 수 있는 위험 요인들을 분석하고자 하였다. 대상 및 방법 ;서울 목동지역 초등학교 1학년의 정기 신체 검사에서 야뇨증 설문지 조사를 통해 일차성 야뇨증으로 확인된 아동 20명과 이후 1년간 이화여자대학교 목동병원 소아과 외래에서 동일한 설문지 조사를 받은 6-7세의 일차성 야뇨증 아동 35명을 포함한 55명을 야뇨증군으로 하였고, 설문지 조사에서 야뇨증이 없었던 아동 221명을 대조군으로 하였다. 이중 야뇨증군 55명과 대조군 22명에서는 24시간 배뇨 일지를 기록하게 하였으며, 두 군사이에 유전적 요인, 심리적 요인, 발달 요인, 수면 요인, 일일 및 야간 수분 섭취량과 요량, 주간 배뇨 장애 및 일회 최대 요량 등을 비교분석 하였다. 결 과 : 1)부모의 야뇨증 병력은 야뇨증군에서 $20.0\%$로 대조군의 $2.7\%$에 비해 유의하게 많았다(P<0.05). 남녀비는 야뇨증군과 대조군에서 유의한 차이가 없었다. 2)출생 순서, 어머니의 직장 여부, 아동과 부모의 성격, 걷기 시작한 나이 및 학교 성적 두 군간에 유의한 차이가 없었다. 3) 잠에서 깨어나기 힘든 경우는 야뇨증군에서 $70.9\%$로 대조군의 $54.3\%$에 비해 유의하게 많았으나(P<0.05), 수면 시간은 차이가 없었다. 4) 야간 수분 섭취량은 야뇨증군에서 $330{\pm}158.2\;mL$로 대조군의 $235{\pm}129.5\;mL$에 비해 유의하게 많았고(P<0.05), 야간 요량은 야뇨증군에서 $390{\pm}61.5mL$로 대조군의 $140{\pm}43.2mL$에 비해 유의하게 많았다(P<0.05). 일일 수분 섭취량과 일일 요량은 두 군간에 유의한 차이가 없었다. 5) 일회 최대 요량은 야뇨증군에서 $107{\pm}35.9mL$로 대조군의 $236{\pm}41.3mL$에 비해 유의하게 적었다((P<0.05). 주간 배뇨 이상은 야뇨증군에서 $80.0\%$로 대조군의 $57.9\%$에 비해 유의하게 많았으며 주간 배뇨 횟수도 야뇨증군에서 $7.0{\pm}3.4$회로 대조군의 $5.4{\pm}1.6$회에 비해 유의하게 많았다(P<0.05). 결 론 :야뇨증은 유전적 요인을 비롯하여 성숙 지연과 관련된 수면 요인, 야간 다뇨, 방광 미숙 등이 관련될 것으로 생각된다. 야간 다뇨의 원인으로 야간 수분 섭취 과다가 관련되므로 치료의 일차 단계로 야간 수분 섭취 제한의 중요성이 강조되어야 한다고 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제8권2호
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• pp.89-94
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• 2004

The arterial pressure is regulated by the nervous and humoral mechanisms. The neuronal regulation is mostly carried out by the autonomic nervous system through the rostral ventrolateral medulla (RVLM), a key area for the cardiovascular regulation, and the humoral regulation is mediated by a number of substances, including the angiotensin (Ang) II and vasopressin. Recent studies suggest that central interleukin-1 (IL-1) activates the sympathetic nervous system and produces hypertension. The present study was undertaken to elucidate whether IL-1 and Ang II interact in the regulation of cardiovascular responses to the stress of hemorrhage. Thus, Sprague-Dawley rats were anesthetized and both femoral arteries were cannulated for direct measurement of arterial pressure and heart rate (HR) and for inducing hemorrhage. A guide cannula was placed into the lateral ventricle for injection of IL-1 $(0.1,\;1,\;10,\;20\;ng/2\;{\mu}l)$ or Ang II $(600\;ng/10\;{\mu}l)$. A glass microelectrode was inserted into the RVLM to record the single unit spike potential. Barosensitive neurons were identified by an increased number of single unit spikes in RVLM following intravenous injection of nitroprusside. I.c.v. $IL-1\;{\beta}$ increased mean arterial pressure (MAP) in a dose-dependent fashion, but HR in a dose-independent pattern. The baroreceptor reflex sensitivity was not affected by i.c.v. $IL-1\;{\beta}$. Both i.c.v. $IL-1\;{\alpha}\;and\;{\beta}$ produced similar increase in MAP and HR. When hemorrhage was induced after i.c.v. injection of $IL-1\;{\beta}$, the magnitude of MAP fall was not different from the control. The $IL-1\;{\beta}$ group showed a smaller decrease in HR and a lower spike potential count in RVLM than the control. MAP fall in response to hemorrhage after i.c.v. injection of Ang II was not different from the control. When both IL-1 and Ang II were simultaneously injected i.c.v., however, MAP fall was significantly smaller than the control, and HR was increased rather than decreased. These data suggest that IL-1, a defense immune mediator, manifests a hypertensive action in the central nervous system and attenuates the hypotensive response to hemorrhage by interaction with Ang II.