• Korean Journal of Clinical Pharmacy
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• v.27 no.4
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• pp.214-220
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• 2017

Background: Dapagliflozin is an oral selective inhibitor of sodium-glucose cotransporter 2(SGLT2), the kidney transporter chiefly responsible for glucose reabsorption from the glomerular filtrate. Because this mechanism does not require the action of insulin, dapagliflozin rarely causes hypoglycemia. Dapagliflozin may affect blood glucose control as well as blood pressure and the body weight which are one of the cardiovascular disease risk factors. However, dehydration and ketoacidosis are reported as the side effects of the dapagliflozin treatment and the safety issues have been occurred. The aim of this study is to analyze the effectiveness and adverse events of dapagliflozin in Korean patients. Methods: From December 2014 to August 2015, we retrospectively reviewed the electronic medical records of type 2 diabetes patients who were prescribed dapagliflozin at Severance Hospital. Results: A total of 202 Korean patients were enrolled in this study. The effectiveness in the reduction of blood glucose was statistically significant(p<0.001). Dapagliflozin decreased 0.74% of HbA1c after 24 weeks. Significantly more participants achieved the target HbA1c level(HbA1c<7%) after 24 weeks(n=42, 35.3%) than before taking dapagliflozin(n=21, 17.6%). Blood pressure decreased 5.7 mmHg systolic blood pressure(SBP), 1.9 mmHg diastolic blood pressure(DBP) after 24 weeks. More than one quarter of participants(n=35, 29.4%) experienced weight loss. Most common adverse event was genitourinary symptoms. Conclusion: In this study, the effectiveness of dapagliflozin in improving glycemic control, blood pressure control, and weight loss was statistically significant. However, elderly and female patients, who have higher incidence of adverse events, should use dapagliflozin cautiously.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.10 no.12
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• pp.3943-3952
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• 2009

This study investigated the changes in bone mineral density(BMD) and biochemical bone turnover markers over 1 year in healthy young college women. In comparison of changes in BMD at the lumbar spine, proximal femur (trochanter, femoral neck, Ward's triangle), and whole body over 1 year, there was only a significant difference in that at forearm. However, serum osteocalcin, a marker of bone formation, and urinary deoxypyridinoline, a marker of bone reabsorption, were significantly changed over 1 year. These findings indicate that although BMD does not significantly change in early young adult, the changes of bone metabolism markers seem to mean active bone turnover in early young adult women.

• Herbal Formula Science
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• v.10 no.1
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• pp.113-129
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• 2002

The present study designed to investigate whether hwangryunhaedok-tang show an anti-hypertensive effect and elucidate its possible mechanism in spontaneously hypertensive rats. The systolic blood pressures (SBP) were significantly decreased as an oral administration of hwangryunhaedok-tang compared with their control group. The urine volume was significantly increased by administration of hwangryunhaedok-tang but urinary sodium (UNaV), potassium (UKV), chloride excretion (UCIV) were not remarkably affected. The urinary creatinine excretion rate (UcrV) was significantly increased in rats administered with hwangryunhaedok-tang in association with increase of creatinine clearance (Ccr). The urine osmolality (Uosmol) was significantly decreased in SHR administered with hwangryunhaedok-tang without being changed in solute-free water reabsorption ( TcH20). The expressions of Aquaporin 2 (AQP-2). 3 and ${\alpha}\;1$, ${\beta}\;1$ subunits of Na.K-ATPase were determined by Western blot analysis to assess the role of these proteins in association with changes of renal functions in SHR administered with hwangryunhaedok-tang. The expression of AQP-2 and 3 protein was significantly down-regulated in the kidney of SHR administered with hwangryunhaedok-tang compared with those in control rats without being altered expression of ${\alpha}\;1$, ${\beta}\;1$ subunits of Na,K-ATPase. In the in vitro assay, Angiotensin converting enzyme (ACE) was inhibited by hwangryunhaedok-tang in a dose-dependent manner. Berberine and/or palmatine, which are well known as a main components of hwangryunhaedok-tang, also have an ACE inhibitory effects in a dose-dependent manner. Taken together, these results suggest that hwangryunhaedok-tang lowered blood pressure through the increase of diuresis caused by down-regulation of water channels and the inhibition of Angiotensin converting enzyme.

• Korean Journal of Pharmacognosy
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• v.12 no.1
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• pp.31-43
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• 1981

In order to determine the effect of Oryeongsan reputed to have diuretic action since Han Dynasty and possible synergetic action of Dianthi Semen, Polygonum avicularis Herba, Kochiae Fructus and Akebiae Lignum, herbs with similar reputation, when added to the above prescription, their decoction powders were solved into distilled water and injected into rabbits through the ear vein. Upon the treatment, the excretion of sodium, potassium and chloride ion together with urine volume was kinetically determined. At the same time the clearance of plasma creatinine and sodium ion was determined and the following results were obtained. Every experimental group demonstrated diuretic action, though feable, of relatively long duration. The diuretic mechanism in the case of Oryeongsan made up by mixing the seperate extracts of individual components and Oryeongsan(A) plus Dianthi Semen was found to be inhibitory effect of renal tubular reabsorption in contrast to the case of Oryeongsan(A) plus Polygonum avicularis Herba, Kochiae Fructus or Akebiae Lignum in which case the diuretic mechanism was found to be glomerular vascular dilatation. The urinary excretion of potassium ion was increased in the case of Oryeongsan(A) plus Dianthi Semen, Kochiae Fructus of Akebiae Lignum whereas in the other cases no similar change was registered. The diuretic action was most remarkable in the case of Oryeongsan(A) plus Polygonum avicularis Herba followed by Oryeongsan(A) plus Kochiae Fructus, Oryeongsan(A) plus Dianthi Semen, extract mixture of individual component of Oryeongsan, Oryeongsan(A) and Oryeongsan(A) plus Akebiae Lignum decreasing order. The duration of diuretic action was found to be 90 minutes in the case of Oryeongsan and mixture of individual component of Oryeongsan, and 60 minutes in the case of Oryeongsan(A) plus Dianthi Semen, Kochiae Fructus or Akebiae Lignum in contrast to the case of Oryeongsan(A) plus Polygonum avicularis Herba which lasted up to 120 minutes.

• The Journal of Internal Korean Medicine
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• v.35 no.1
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• pp.106-110
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• 2014

Objectives : To report a case of the treatment of primary hypertension by Oryung-san (五苓散: Wulingsan in Chinese, Goreisan in Japanese) monotherapy. Methods : The blood pressure (BP) fluctuation was checked of a woman who had sudden BP elevation without a history of hypertension treatment. There were no specific history of disease and results for the laboratory examination and image diagnosis including MRI. The woman was diagnosed with primary hypertension and she was given supple of Oryung-san extract (Hanpoong Pharm Co.) 3 g, three times a day for three months. The BP has been checked with digital sphygmomanometer (HEM-7111, Omron Japan) in brachial artery at home. Results and Conclusions : The patient had had stable BP since three weeks after Oryung-san treatment was initiated. There were no subjective symptoms, then Oryung-san medication also had quit after three months treatments. This shows some possibility to control hypertension using Oryung-san, which resembles thiazide that acts on the distal convoluted tubule and inhibit sodium-chloride reabsorption. For further evaluation of the effectiveness, well-designed randomized controlled trials should be undertaken.

• Archives of Plastic Surgery
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• v.43 no.2
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• pp.204-209
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• 2016

Temporal hollowing occurs to varying degrees after pterional craniotomy. The most common cause of temporal hollowing is a bony defect of the pterional and temporal regions due to the resection of the sphenoid ridge and temporal squama for adequate exposure without overhang. The augmentation of such bony defects is important in preventing craniofacial deformities and postoperative hollowness. Temporal cranioplasty has been performed using a range of materials, such as acrylics, porous polyethylene, bone cement, titanium, muscle flaps, and prosthetic dermis. These methods are limited by the risk of damage to adjacent tissue and infection, a prolonged preparation phase, the possibility of reabsorption, and cost inefficiency. We have developed a method of temporal augmentation using a calvarial onlay graft as a single-stage neurosurgical reconstructive operation in patients requiring craniotomy. In this report, we describe the surgical details and review our institutional outcomes. The patients were divided into pterional craniotomy and onlay graft groups. Clinical temporal hollowing was assessed using a visual analog scale (VAS). Temporal soft tissue thickness was measured on preoperative and postoperative computed tomography (CT) studies. Both the VAS and CT-based assessments were compared between the groups. Our review indicated that the use of an onlay graft was associated with a lower VAS score and left-right discrepancy in the temporal contour than were observed in patients undergoing pterional craniotomy without an onlay graft.

• Journal of Pharmaceutical Investigation
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• v.21 no.1
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• pp.33-41
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• 1991

A high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of theophylline(TP) and its metabolites, 1-methyluric acid (1-MU) and 1,3-dimethyluric acid (1,3-DMU), in rat plasma and urine. An $100\;{\mu}l$ aliquot of a plasma or urine sample was mixed with $250\;{\mu}l$ of acetonitrite and vortexed. After centrifugation, $200\;{\mu}l$ (plasma) or $20\;{\mu}l$ (urine) aliquot of the supernatant was dried by $N_2$ stream and redissolved in $100\;{\mu}l$ (plasma) or $200\;{\mu}l$ (urine) of the mobile phase. A $20\;{\mu}l$ of the mobile phase solution was injected onto a $C_{18}$ reversed-phase column. The column was maintained at $45^{\circ}C$ by the aid of electric heating jacket. The mobile phase was a 3%(v/v) methanol solution in deionized water which contains sodium acetate (100 mM) and tetrabutyl ammonium hydroxide (4 mM). pH of the mobile phase was adjusted 4.5 by the addition of acetic acid. Detection limits for TP, 1-MU, and 1,3-DMU in plasma were 0.2, 0.1 and $0.1\;{\mu}/ml$, respectively and the corresponding values in urine were all $5\;{\mu}g/ml$. Inter- and intra-day variability of the assay for all compounds in the plasma samples was less than 5.5 and 3.8%, respectively. The retention times for 1-MU, 1,3-DMU, and TP were approximately 7, 8.5 and 18 min, respectively. Sample preparation procedure used in this method was simple, rapid and reproducible. Renal clearance of TP and its metabolites in rats showed plasma concentration dependency indicating renal tubular secretion and reabsorption of them.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.1
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• pp.69-76
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• 1998

Cis-diamminedichloroplatinum II (cisplatin), an effective antitumor agent, induces acute renal failure by unknown mechanisms. To investigate direct toxic effects of cisplatin in the renal proximal tubular transport system, OK cell line was selected as a cell model and $Na^+/H^+$ antiport activity was evaluated during a course of cisplatin treatment. The cells grown to confluence were treated with cisplatin for 1 hour, washed, and incubated for up to 48 hours. At appropriate intervals, cells were examined for $Na^+/H^+$ antiport activity by measuring the recovery of intracellular pH (pHi) after acid loading. Cisplatin of less than 50 ${\mu}M$ induced no significant changes in cell viability in 24 hours, but it decreased the viability markedly after 48 hours. In cells exposed to 50 ${\mu}M$ cisplatin for 24 hours, the $Na^+-dependent$ pHi recovery (i.e., $Na^+/H^+$ antiport) was drastically inhibited with no changes in the $Na^+-independent$ recovery. Kinetic analysis of the $Na^+-dependent$ pHi recovery indicated that the Vmax was reduced, but the apparent Km was not altered. The cellular $Na^+$ and $K^+$ contents determined immediately before the transport measurement appeared to be similar in the control and cisplatin group, thus, the driving force for $Na^+-coupled$ transport was not different. These results indicate that cisplatin exposure impairs the $Na^+/H^+$ antiport capacity in OK cells. It is, therefore, possible that in patients treated with a high dose of cisplatin, proximal tubular mechanism for proton secretion (hence $HCO_3^-$ reabsorption) could be attenuated, leading to a metabolic acidosis (proximal renal tubular acidosis).

• The Korean Journal of Physiology
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• v.8 no.1
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• pp.7-14
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• 1974

This study was carried out to investigate the acute changes in R-A-A system following lasix administration, and to evaluate the materials in plasma R-A-A system and electrolytic excretion every 30 minutes for 2 hours after lasix administration with normal high sodium Korean food, moderate sodium restriction, and severe sodium restriction, and it was concluded as followed; 1. Plasma renin activity, angiotensin II concentration, and aldosterone concentration elevated in course of time after lasix administration with high sodium Korean food, but the R-A-A system takes insignificant part because of the increasing rate was so slight. 2. Although the increasing rate of plasma renin activity reached lower levels, angiotensin II and aldosterone concentration were significantly increased after lasix administration with moderate sodium restriction. 3. It was observed that higher rise in aldosterone concentration following lasix administration during severe sodium restriction than when moderate sodium restriction. 4. Urinary sodium and potassium excretion during two hours after lasix administration showed decrease as little as the amount of sodium intake, but K/Na excretion ratio showed increase with small amount of sodium intake because of the decreasing rate of potassium was low value. 5. Sodium excretion after lasix administration reached more than 1.5 times of sodium intake, even though R-A-A reaction showed significantly. 6. As our results showed, R-A-A reaction following acute diuresis was insignificant with high sodium Intake, the increasing ratio of aldosterone concentration showed high rise compare with of plasma renin activity as little as the amount of sodium intake, and the participated rate in sodium reabsorption of R-A-A system was increased.

• Journal of Nutrition and Health
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• v.34 no.2
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• pp.150-157
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• 2001

Intestinal absorption of dietary taurine is one of the regulatory component maintaining taurine homeostasis along with renal reabsorption, bile acid conjugation and secretion, and de nobo synthesis of taurine in mammals. Recent observations of decreased enterocytic levels of taurine in response to trauma, infection and surgical insults, postulate the possibility that intestinal taurine absorption might be impaired in such stressed conditions. The aim of the present study was to evaluate changes in enterocytic taurine transporter activity using the human intestinal colon carcinoma cell line, HT-29, in various stress-induced conditions. Pretreatment of the HT-29 cells with dexamethasone, a stress hormone(0.1,1,10 or 100$\mu$M) for 3 hrs, or with E coli heat-stable enterotoxin(10, 100, or 200nM) for 30 minutes in order to induce the condition of enterotoxigenic infection did not influence taurine uptake as compared to the value found in control cells. In contrast, pretreatment of the cells with cholera toxin(10, 100, 500, or 1000ng/ml)for 3hr or 24hr significantly decreased taurine uptake by HT-29 cells to 40~50% of the value found in untreated control cells. Kinetic studies of the taurine transporter activity were conducted in control and cholera toxin treated HT-29 cells with varying taurine concentrations(2~60$\mu$M) in the uptake medium. Pretreatment of the cells with cholera toxin(100ng/ml) for 3hr did not influence the Vmax, but resulted in a 55% increase in the Michaelis-Menten constant(Km) of the taurine transporter compared to those in control cells. These results suggest that cholera toxin-induced reduction in taurine transporter activity in HT-29 cells is associated with decreased affinity of the taurine transporter without altering the amount of transporter protein. Intestinal taurine absorption appears to be reduced in the condition of water-borne diseases caused by bacteria such as V. cholerae. This might influence the taurine status of infants and young children more readily, an age group in which the prevalence of intestinal infection is high and the role of intestinal absorption is crucial for maintaining the body taurine pool. (Korean J Nutrition 34(2) : 150-157, 2001)