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Studies on the diuretic activity of the serum of the patient with diabetes insipidus

Journal of the Korean Pediatric Society 1976;19(2):99-112.
Published online February 28, 1976.
Studies on the diuretic activity of the serum of the patient with diabetes insipidus
Kook-Choo Rie, Yong-Soo Yun, Ho-Sung Lee, Jeong-Ki Seo, Dong-Hwan Lee
Department of Pediatrics, College of Medicine,Seoul National University,Seoul, Korea
尿殷症患者 血淸의 利尿作用에 關한 硏究
李國往, 尹龍洙, 李鎬成, 徐起現, 李東換
서울大學校 醫科大學 小兒科學敎室
Diabetes insipidus is the syndrome which results from abnomality in production or release of ADH. Recently there have been used two nonhormonal forms of therapy in the treatment of DI: 1)Various diuretics, primarily thiazides and 2)The oral hypoglycemic agents, the sulfonlureas. Arduino and other numerous invesgators demnstrated that sulfonylurea chlorpropamide (Diabinase) and tolbutamide(Drinase) had a ADH-Iike effect in a patient with diabetes insipidus, but it had no effect in nephrogenic DI. When the thiazides or other diuretic is administered with enough sodium chloride to prevent negative salt balance the antidiuretic effect does not occur. The sulfoureas act through a mechanism distinctly different from that of the thiazides. An interesting clinical observation shows that patients with complete DI who have none ADH in there circulation do not respond to oral or parenteral chlorpropamide or tolbutamide. Ingelfiger and Hays have carried out in vitro expriments on the toad bladder and found that chlorpropamide alone had no effect on water movements across the toad bladder. However, when vasopressin in low concentration was added to the bladder water movement became significantly increased. These observation led Ingelfinger and Hays to the conclusion that the sulfonylureas enhance the sensitivity of the distal tuble to trace amounts of vasopressin that persist in patent with incomplete diabetes insipidus. On the other hand, Author and coworkers demonstrated strong diuretic substance in the serum of the rabbit which were stimulated osmotically with hypotonic solution in the anterior hypothalamus, ligated jugular vein bilaterally, or ligated kidney vein and in the serum of the patients with nephrotic syndrome in diuretic phase. As Authors have had the opportunity of observation on the patient with DI resulted from tuberculous meningitis, made the experimental studies to know whether the serum of the patient have some diuretic and antidiuretic ability, or this study serve a useful test to predict the effect of chlorpropamide, or diuretic substance, if it can be demonstrated, serve the- rapeutic effect in the treatment of DI as diuretics.Korean white male rabbits weighing 2kg were used in this work. They were well hydrated orally by gaveging with lOOcc of 2% sodium chloride solution three times at one hour interval to maintain positive water balance. 1.0ml of serum of patient or rabbits were given intravenously. Urine was collected through a indwelling catheter while the rabbits were placed on the holder. 10mg of diabinase per day were given oraly in the rabbits on the control study. Patient: W.J. Yang, Male, 24.5kg Chief complaints: Polyuria and polydipsia. The diagnosis assured by the water restriction test, hypertonic saline infusion test and pitressin test. 125mg of diabinase per day were given orally in the treatment. The following results were obtained. 1)The urinary excretion of the hydrated rabbits decreased markedly by the injection of 1.0ml of serum of the patient derived before diabinase administration. From above result, some potent antidiuretic substance exsists in the serum of the patient is now clearly established and at the same time this data may predict the effect of diabinase in the treatment of this patient. 2)The antidiuretic activity of the serum of the patient derived before the treatment disappeared in the period which the symptoms much improved after diabinase administration. And the serum dirived in this period showed marked diuretic activity occasionaly. 3)The antidiuretic activity of the serum of the patient reappeared in the period of aggravation by the discontinuance of diabinase. 4) The serum derived from the rabbits which were administered 10mg of diabinase per day showed potent antidiuretic activity first and also showed diuretic activity later. 5)Above results give us the suggestion that the diuretic activity in the serum of the patient derived after diabinase administration may have some influence on the treatment of DI.

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