• Journal of Pharmaceutical Investigation
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• 제13권2호
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• pp.73-87
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• 1983

The matrix affects the dissolution of furosemide, which is almost insoluble in the dissolution medium. In order to understand the effect of the matrix on the dissolution of furosemide, lactose, starch, $Avicel\;^{\circledR}pH\;101$, $Avicel\;^{\circledR}pH\;301$, $SiO_2$ and talc were used as the matrix and the solvent deposition method were used. The dissolution characteristics of four dissolution medium were compared to each other using various ratio of drug-to-matrix. The results are as follows: 1) Lactose was shown to be superior and talc was to be inferior to the other matrixes investigated. 2) A maximum dissolution rate and dissolution amount of furosemide were observed in 1 : 10 ratio of the drug-to-matrix. 3) $T_{80%}$ of 1 : 10 ratio of the drug-to-matrix in pH 7.2 was 1 min. from FM-lactose and 30 min. from FM-talc. $T_{50%}$ in pH 4.2 is 2 min. from furosemide-lactose and 150 min. from furosemide-talc. Total amount of furosemide in pH 1.2 at 30 min. were enhanced 13.3 fold in furosemide-lactose and 3.5 fold in furosemide-talc compared to the control. Diuretic action of those furosemide-lactose and furosemide-talc was also evaluated by monitoring changes in urinary excretion of sodium, potassium and urine volume in rat. The accumulated urine volume were enhanced 1.7 fold in furosemide-lactose (1.5) compared to the furosemide.

• 동의생리병리학회지
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• 제20권1호
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• pp.181-186
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• 2006

A pharmacological inhibition of nitric oxide synthase (NOS) in rats produces vasoconstriction, renal dysfunction, and hypertension. The present study was aimed at investigating whether the methanol extract of Serous commixta cortex (MSC) ameliorates $N^G$-nitro-L-arginine methylester (L-NAME) induced hypertension in rats. Treatment of rats with L-NAME (10 mg/kg/day in drinking water, 5 weeks) caused a sustained increase in systolic blood pressure (SBP). Administration of MSC (100 or 200 mg/kg/day, p.o) significantly lowered the SBP in the L-NAME-treated rats and this effect was maintained throughout the whole experimental period. Moreover, ecNOS expression in aorta and kidney tissue from L-NAME treated rats was significantly restored dy administration of MSC. Furthermore, the impairment of acetylcholine (ACh)-induced relaxation of aortic rings in the L-NAME treated rats was reversed dy administering of MSC. The renal functional parameters including urinary volume, sodium excretion, and creatinine clearance (Ccr) were also restored by administering MSC. Taken together, the present study suggeststhat MSC prevents the increase in SBP in rats with L-NAME-induced hypertension, which may result from the up-regulation of the vascular and renal ecNOS/No system.

• Childhood Kidney Diseases
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• 제20권1호
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• pp.11-17
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• 2016

Appropriate control of diet and water intake is important for maintaining normal blood pressure, fluid and electrolyte homeostasis in the body. It is relatively understood that the amount of sodium and potassium intake directly affects blood pressure and regulates ion transporters; Na and K channel functions in the kidney. However, little is known about whether diet and water intake regulates Aquaporin (AQP) function. AQPs, a family of aquaporin proteins with different types being expressed in different tissues, are important for water absorption by the cell. Water reabsorption is a passive process driven by osmotic gradient and water permeability is critical for this process. In most of the nephron, however, water reabsorption is unregulated and coupled to solute reabsorption, such as AQP1 mediated water absorption in the proximal tubule. AQP2 is the only water channel founded so far that can be regulated by hormones in the kidney. AQP2 expressed in the apical membrane of the principal cells in the collecting tubule can be regulated by vasopressin (antidiuretic hormone) controlling the final volume of urine excretion. When vasopressin binds to its receptor on the collecting duct cells, it stimulates the translocation of AQP2 to the membrane, leading to increased water absorption via this AQP2 water channel. However, some studies also indicated that the AQP2 is also been regulated by vasopressin independent mechanism. This review is focused on the regulation of AQP2 by diet and the amount of water intake on salt and water homeostasis.

• 비만대사연구학술지
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• 제1권2호
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• pp.78-82
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• 2022

Liraglutide (Saxenda^R) is prescribed to induce and sustain weight loss in obese patients. The starting dose of liraglutide is 0.6 mg/day for 1 week, which is increased by 0.6 mg/day every week until the full maintenance dose of 3 mg/day is achieved. Such dose titration is needed to prevent side effects, which primarily include gastrointestinal problems such as nausea, diarrhea, constipation, vomiting, dyspepsia, and abdominal pain. A 35-year-old, reportedly healthy obese man receiving liraglutide treatment for obesity visited the emergency room complaining of generalized weakness and dizziness accompanied by repeated diarrhea and vomiting. He reported over 20 episodes of diarrhea starting the day after liraglutide dose escalation from 1.2 mg/day to 1.8 mg/day. Laboratory findings suggested pre-renal acute kidney injury, including serum creatinine 4.77 mg/dl, blood urea nitrogen (BUN) 37 mg/dl, estimated glomerular filtration rate (eGFR) 15 ml/min/1.73 m², and Fractional excretion of sodium 0.08. After volume repletion therapy, his renal function recovered to a normal range with laboratory values of creatinine 1.08 mg/dl, BUN 14 mg/dl, and eGFR 88 ml/min/1.73 m². This case emphasizes the need for caution when prescribing glucagon-like peptide-1 receptor agonists, including liraglutide, given the risk of serious renal impairments induced by volume depletion and dehydration through severe-grade diarrhea and vomiting.

• 대한약리학회지
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• 제22권2호
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• pp.79-87
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• 1986

중추 dopamine(DA)계가 신장기능 조절에 관여하고 있으며 뇌실내로 DA를 투여하면 norepinephrine(NE)처럼 항이뇨와 항Na 배설을 초래함이 보고된 바 있고, 중추 DA작용에 있어서 adrenergic system이 관여한다는 많은 시사가 있다. 따라서 본 연구에서는alpha-2 adrenocopter 차단제인 yohimbine이 측뇌실내 DA의 신장작용에 어떠한 영향을 미치는가를 관찰하였다. Yohimbine $100\;{\mu}g/kg$을 가토측뇌실내로 투여시(icv) 신혈류 및 사구체 여과율의 감소와 함께 현저한 항이뇨 및 Na 배설감소를 초래하였으며, DA $15\;{\mu}g/kg$ icv 역시 항이뇨를 초래하였으나 yohimbine 전 처치후에는 뇨량 및 Na배설의 증가를 초래하였다. 양을 더올려 $150\;{\mu}g/kg$의 DA를 yohimbine 전처치 가토에 투여하면 3배 이상의 Na배설 증가와 함께 현저한 이뇨작용이 나타났으며 이 작용은 약 20분간 지속되었다. 이때 신혈류 역학은 일부 개선되었다. 다른 DA agonist인 apomorphine은 $100\;{\mu}g/kg$ icv로 현저한 이뇨와 Na 배설증가를 나타내며 신혈류역학도 개선하였으나, yohimbine은 이같은 apomoiphine작용을 차단하지 못하였다. NE $10\;{\mu}g/kg$ icv도 항이뇨 작용을 나타냈으나 yohimbine 전처치에 의하여 차단되지 아니하였다. 이 연구결과로, 중추 DA의 신장작용은 NE처럼 단순하지 않고, 이뇨작용은 신혈류역학의 감퇴에 기인한 항이노작용에 의해 은폐되어 있으며, yohimbine은 DA의 항이뇨작용은 차단하나 이뇨작용에는 영향을 미치지 못하며, DA의 항이뇨작용이 지양될때에만 이뇨작용이 발현됨을 알 수 있었다. 또한 중추를 통한 DA의 신장작용에는 adrenergic system이 관여하지 않은 것으로 보인다.

• 대한약리학회지
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• 제26권2호
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• pp.153-160
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• 1990

5-Hydroxytryptamine(5-HT)를 가토뇌실내로 투여 (icv)하면 이뇨와 Na배설증가가 초래되며, 이러한 작용은 $5-HT_1$ 수용체길항제인 methysergide에 의하여 차단되므로 중추성 신장기능조절에 있어 중추 tryptamine계의 관련이 시사된 바 있다. 본 연구에서는 $5-HT_2$ 길항제로 알려진 ketanserin (KET)를 이용하여 $5-HT_2$ 수용체의 역할을 구명하고자 하였다. KET $120\;{\mu}g(=0.3{\mu}moles)/kg$ icv는 신혈류역학에는 아무런 변동을 일으키지않으나 유의한 Na배설증가를 초래하여, 세뇨관에서의 Na 재흡수 감소가 시사되었다. 전신혈압은 약간 감소하였다. 정맥내 투여시에는 유의한 기능변동을 볼 수 없었다. 5-HT $200{\mu}g/kg$ icv는 경미하나 유의한 Na배설증가 및 이뇨작용을 나타냈다. 그러나 신장기능에 그다지 큰 영향을 미치지 않는 양인 $40{\mu}g/kg$의 KET icv후에는 5-HT의 작용이 크게 강화되어, Na배설분획이 9.3%에 달하였다. Norepinephrine, dopamine, histamine과 같은 다른 생체아민의 신장작용은 KET전처치에 의하여 영향받지 아니하였다. 본 연구는 중추 $5-HT_1$ 수용체와는 반대로 중추 $5-HT_2$ 수용체는 항이뇨 및 Na배설감소를 매개하고 있으며, 중추 tryptamine계는 신장기능을 이중적으로 조절하고 있음을 시사하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제16권2호
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• pp.91-95
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• 2012

The role of the kidney in combating metabolic acidosis has been a subject of considerable interest for many years. The present study was aimed to determine whether there is an altered regulation of renal acid base transporters in acute and chronic acid loading. Male Sprague-Dawley rats were used. Metabolic acidosis was induced by administration of $NH_4Cl$ for 2 days (acute) and for 7days (chronic). The serum and urinary pH and bicarbonate were measured. The protein expression of renal acid base transporters [type 3 $Na^+/H^+$ exchanger (NHE3), type 1 $Na^+/{HCO_3}^-$ cotransporter (NBC1), Na-$K^+$ ATPase, $H^+$-ATPase, anion exchanger-1 (AE-1)] was measured by semiquantitative immunoblotting. Serum bicarbonate and pH were decreased in acute acid loading rats compared with controls. Accordingly, urinary pH decreased. The protein expression of NHE3, $H^+$-ATPase, AE-1 and NBC1 was not changed. In chronic acid loading rats, serum bicarbonate and pH were not changed, while urinary pH was decreased compared with controls. The protein expression of NHE3, $H^+$-ATPase was increased in the renal cortex of chronic acid loading rats. These results suggest that unaltered expression of acid transporters combined with acute acid loading may contribute to the development of acidosis. The subsequent increased expression of NHE3, $H^+$-ATPase in the kidney may play a role in promoting acid excretion in the later stage of acid loading, which counteract the development of metabolic acidosis.

• Childhood Kidney Diseases
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• 제2권2호
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• pp.133-137
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• 1998

목 적 : 1987년 정주용 면역글로불린(Intravenous immunoglobulin: IVIG)에 의한 급성신부전의 첫 증례가 보고된 이후 성인에서는 고용량의 IVIG와 관련된 신손상의 보고들이 다수 있었다. 이에 저자들은 고용량 IVIG의 사용이 보편화되어 있는 가와사끼병과 특발성 혈소판 감소성 자반증 환아에서 IVIG의 신독성 여부를 관찰하고자 하였다. 방 법 : 1996년 1월에서 8월까지 이대 부속 목동 병원에 입원하여 가와사끼병(23례)과 특발성 혈소판 감소성 자반증(7례)으로 고용량의 정주용 면역글로불린(2 g/kg)을 투여받은 환아를 대상으로 하였다. IVIG투여후 1일, 3일에 요량, BUN, 혈청 creatinine, Ccr, FENa, TRP, 24 시간뇨 ${\beta}_2$-microglobulin/cr 비 및 microalbumin/cr 비의 변화를 관찰하였다. 통계는 repeated measurement ANOVA test와 t-test를 사용하여 검정하였다. 결 과 : 고용량의 IVIG 투여후에 요량, BUN, 혈청 creatinine, Ccr, TRP, 24 시간뇨 ${\beta}_2$-microglobulin/cr 비 및 microalbumin/cr비의 유의한 변화는 없었다. IVIG투여후 1일에 일시적으로 증가한 FENa만이 유의한 변화였다. 결 론 : 소아에서 흔히 사용되는 고용량 IVIG는 정상 신기능 상태에서는 유의한 신손상을 일으키지 않았다.

• 한국임상수의학회지
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• 제32권1호
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• pp.1-4
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• 2015

개의 10번 염색체에 존재하는 Copper metabolism domain containing 1 (COMMD1) 유전자는 체내 구리 대사를 조절하는 COMMD1 단백질을 합성한다. COMMD1 유전자의 exon 2 결손변이는 단백질의 결핍을 유발하여 베들링턴 테리어 견종에서 상염색체 열성 유전질환인 구리 중독증을 일으킨다. 본 증에 이환된 개체는 담즙을 통한 구리의 배설이 저해되어 간 내에 구리가 축적된다. 본 연구에서는 국내 베들링턴 테리어 257두(수컷 109두, 암컷 148두) 혈액 시료를 사용하여 genomic DNA를 추출하였다. 유전자 결손변이의 분자생물학적 진단을 위해 다중 중합효소 연쇄반응법(multiplex PCR)을 이용하여 COMMD1 유전자의 exon 2 결손 발생 및 그 빈도를 조사하였다. 베들링턴 테리어 257두에서, 정상유전자 동협접합자가 131두(51%), 이형접합자가 108두(42%), 변이유전자 동형접합자가 18두(7%)로 확인되었다. 본 연구를 통해 한국 베들링턴 테리어 개체군의 유전변이 발생 및 그 빈도를 확인하였고, 이는 국내 베들링턴 테리어 개체군의 유전자 선택적 교배계획 설립 및 변이 유전자 확산을 예방하기 위한 기초 자료로서 의의가 있다.

• Asian-Australasian Journal of Animal Sciences
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• 제28권1호
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• pp.37-49
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• 2015

During pregnancy, the maternal body undergoes significant physiological changes. The present study assessed the changes on calcium (Ca), phosphorus (P), magnesium (Mg), sodium (Na) and potassium (K) metabolism in singleton and twin-pregnant dairy goats. The 42 goats used ($49.5kg{\pm}7.6$ body weight [BW]) were assigned at random to treatments that were factorially arranged to account for 2 breeds (Oberhasli and Saanen), 2 pregnancy types (singleton and twin) and 3 gestation periods (80, 110, and 140 days). Digestibility trials were performed at 80, 110, and 140 days of gestation. Mineral retention during pregnancy was determined in the maternal body, femur, uterus, mammary gland, fetus and fetal fluid. Blood samples were taken during pregnancy before and after a meal, and Ca, P, Mg, Na, K ions and alkaline phosphatase activity determined in serum. Bone mineral density was determined in the right femur. Statistical analyses were performed using the SAS MIXED procedure. Dry matter intake decreased linearly up to 140 days of gestation. Maternal BW gain, and Ca, P, and Mg retention (g/kg) decreased linearly with the advance of gestation days. Macromineral retention in maternal body (g/kg) was greater in Oberhasli than Saanen goats, and their fetuses had higher Ca, P, and Mg deposition (mg/g). Mineral retention (mg/g) increased in fetuses according to pregnancy development, with no differences between singleton and twin pregnancy. In the mammary gland, the retention of all minerals (g) increased with the days of pregnancy. In conclusion, related to Ca, P, and Mg metabolism can be divided into two stages. Up to 80 days of gestation, was characterized by the preparation of the maternal body reserves for future mineral demands. From 80 days of gestation onward, was characterized by the transfer of maternal body reserves for fetal development and colostrum production. Na and K supply was provided by adjustments in endogenous excretion and an increase in intestinal absorption. Finally, mineral metabolism was specific to each genotype and, except for Na, was not affected by the number of fetuses.