• Molecules and Cells
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• v.26 no.5
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• pp.468-473
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• 2008

Low-density lipoprotein (LDL) induces cell proliferation in human aortic smooth muscle cells (hAoSMCs), which may be involved in atherogenesis and intimal hyperplasia. Recent studies have demonstrated that $Cl^-$ channels are related to vessel cell proliferation induced by a variety of stimuli. In this study, we investigated a potential role of $Cl^-$ channels in the signaling pathway of LDL effects on hAoSMC proliferation with a focus on the activation of Erk1/2-PI3K/Akt and the subsequent upregulation of Egr-1. $Cl^-$ channel blockers, DIDS, but neither NPPB nor Furosemide, completely abolished the LDL-induced DNA synthesis and cell proliferation. Moreover, DIDS, but not NPPB, significantly decreased LDL-stimulated $Cl^-$ concentration, as judged by flow cytometry analysis using MQAE as a $Cl^-$-detection dye. DIDS pretreatment completely abolished the activation of Erk1/2 and PI3K/Akt in a dose-dependent manner that is the hallmark of LDL activation, as judged by Western blot and proliferation assays. Moreover, pretreatment with DIDS ($Cl^-$ channel blockers) but not LY294002 (PI3K inhibitors) completely abolished the LDL-induced upregulation of Egr-1 to the same extent as PD98059 (MEK inhibitors to inhibit Erk), as judged by Western blot and luciferase reporter assays. This is the first report, to our knowledge, that DIDS-sensitive $Cl^-$-channels play a key role in the LDL-induced cell proliferation of hAoSMCs via the activation of Erk1/2 and PI3K/Akt and the upregulation of Egr-1.

• Childhood Kidney Diseases
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• v.13 no.1
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• pp.84-91
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• 2009

We experienced a female neonate with congenital nephrotic syndrome (CNS) associated with congenital diaphragmatic hernia (CDH). Because of the rare combination of two conditions, we report this case with literature review. CDH was found immediately after birth and emergency operation was done for hernia repair. But on the next day, generalized edema and oliguria(0.59 mL/kg/hour) was found and her blood chemistry showed hypoalbuminemia (1.6 g/dL), increased BUN (27.7 mg/dL) and serum creatinine( 1.8 mg/dL) along with heavy proteinuria (4+). We started albumin infusion with a bolus of intravenous furosemide. We suspected the neonate had congenital nephrotic syndrome and her 24hr urine protein was 1,816 mg/day. In spite of immunosuppressive therapy, the nephrotic syndrome and renal failure progressed. We started peritoneal dialysis on the day of life 22 but it was not satisfactory. She was complicated by intracranial hemorrhage and multi-organ failure and expired at 34 days of age. Kidney necropsy was performed which showed diffuse mesangial sclerosis (DMS). Her chromosome study revealed 46, XX and her gene study revealed a heterozygous missense mutation, Arg366His, in Wilms tumor suppressor gene (WT1). This case deserves attention on account of the 4th case of CNS with CDH revealing the Arg366His mutation in the WT1 gene and G the 1st case of early onset renal failure without male pseudohermaphroditism and Wilms tumor with CNS, CDH and the Arg366His mutation in the WT1 gene. So, this report gives support to the hypothesis that Arg366His mutation in the WT1 gene can result in CNS and CDH.

• Journal of Yeungnam Medical Science
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• v.3 no.1
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• pp.313-318
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• 1986

Primary aldosteronism is a disease that the stimulus for the excessive aldosterone production resides within the adrenal gland. It was first described by conn in 1955. And many cases were reported by physicians at present in the world. But it is relatively rare in Korea, probably due to lack of attension and medical facilities. Only about 13 cases have been reported at present. The clinical, biochemical features in 1 case of primary aldosteranism caused by adrenal hyperplasia that was diagnosed at Yeungnam University Hospital was observed and the following result were obtained. 1. Clinical feature: The present case was 27-year-old woman who was admitted due to general weakness and easy fatigability. The above mensioned chief complaints occurred 8 months prior to admission when she delivered of second baby by cesarian section. Symptoms such as above chief complaints, intermittent muscle paralysis and cramping were noticed. Trousseau's sign was also present. The average blood pressure ranged from 170/90 to 200/120. 2. Biochemical abnormalities: Severe hypokalemia lower than 2.5 mEq/L was presented and 24 hours urine potassium showed markedly increased urinary loss.(228 mEq/day). Plasma renin activity was decreased under normal range with furosemide administration.(Basal renin; 0.01ng/ml/hr, stimulated renin 0.12ng/ml/hr). Saline suppression test revealed markedly elevated levels of aldosterone higher than normal range. (Basal aldosterone; 320.68pg/ml stimulated aldosterone; 451.86pg/ml). And posture test showed decreased plasma renin activity and increased plasma aldosterone level. - PRA(ng/ml/hr)=Bsal: 0.05(0.15~2.33), Stimulated: 0.22(1.31~3.95) - Aldosterone(pg/ml)=Bsal: 242.77(10~160), Stimulated: 432.09(40~310) 3. Adrenal CT scan revealed no abnormal findings. 4. Treatment and course: Spironolactone was given at OPD with regular follow-up. Her blood pressure ranged from 150/90 to 160/100 and symptoms were improved. The effect of treatment was satisfactory and further follow up would be performed.

• Journal of Pharmaceutical Investigation
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• v.35 no.5
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• pp.323-328
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• 2005

The purpose of the present study was to evaluate the bioequivalence of two torasemide tablets, Torem tablet (Roche Korea Co., Ltd., Korea, reference drug) and Boryung Torsemide tablet (Boryung Pharmaceutical Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (furosemide) to human serum, serum samples were extracted using 5 mL of ethyl acetate. Compounds were analyzed by reverse-phase HPLC method with UV detection. This method showed linear response over the concentration range of 0.05 ug/mL with correlation coefficient of 0.999. The lower limit of quantitation using 0.5 mL of serum was 0.05 ug/mL which was sensitive enough for pharmacokinetic studies. Twenty-eight healthy male Korean volunteers received each medicine at the torasemide dose of 20 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Serum concentrations of torasemide were monitored by an HPLC-UV for over a period of 12 hr after the administration. $AUC_{t}$(the area under the serum concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum serum drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the serum concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_{t}$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_{t}$ ratio and the $C_{max}$ ratio for Boryung Torsemide/Torem were log 0.97-10g 1.03 and log 0.93log 1.12, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Boryung Torsemide tablet and Torem tablet are bioequivalent.

• Korean Journal of Clinical Pharmacy
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• v.22 no.4
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• pp.330-339
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• 2012

Background : Hypertension is treated with both lifestyle modification and pharmacotherapy. The Seventh Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7), published in 2003, provides a streamlined management approach to hypertension for the primary care physician. The JNC-7 is the gold standard also in Korea. According to the JNC-7, special therapeutic considerations are recommended for high-risk individuals with compelling indications. The presence of compelling indications in any given patient should be considered when selecting specific pharmacotherapy to treat hypertension. However, in patients with compelling indications, it is unknown that hepatotoxicity is caused by Calcium Channel Blocker (CCB), one of 1st anti-hypertensive drugs. Now, the CCB is the most used 1st anti-hypertensive drug in Korea Therefore, we evaluated the changes in blood liver function parameters (ALT, AST, Total bilirubin, serum albumin) for the study group. Methods : We randomly collected and retrospectively analyzed Electronic Medical Record data (n=28,788) of patients, and who took calcium channel blockers(non-dihydropyridines; diltiazem, verapamil, dihydropyridines; amlodipine, barnidipine, benidipine, clinidipine, efonidipine, felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine), with having liver function tests (LFTs) from July 1st 2009 to June 30th 2010 at the Seoul National University Hospital in Korea. Control groups are two antihypertensive agents: RAS blockade (ARB; candesartan, irbesartan, losartan, olmesartan, telmisartan, valsartan, ACE-I; cilazapril, enalapril, fosinopril, imidapril, perindopril, ramipril) and, Diuretics (loop; furosemide, torsemide, thiazide; hydrochlorothiazide[HCTZ], indapamide). Patients not having LFT results at these three standard points of time(baseline, during, medication, and after finishing medication) were excluded. The collected data were analyzed by using the SPSS (Version12.0) and Microsoft Excel (Version2007). Results : 711 patients who were treated CCB (297), RAS blockade (232) or Diuretics (182) monotherapy were selected for the study. In selected patients, liver damage degree(changes of each LFTs value) was higher in diuretics group than other groups, followed by RAS blockade and CCB. In diuretics group's was loop-diuretics group was higher than thiazide-diuretics group. In CCB group, Nondihydropyridine-CCB's damage degree was higher than Dihydropyrine-CCB's that. Conclusions : Despite the limitations due to the retrospective study, among patients with abnormal LFTs, the use of CCBs led to a less liver damage than other 1st anti-hypertensive agents. It can be recommended CCBs as one of the initial treatments of hypertension in patients with liver disease.

• Childhood Kidney Diseases
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• v.11 no.1
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• pp.106-111
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• 2007

[ $Henoch-Sch\ddot{o}nlein$ ] Purpura(HSP) is a form of vasculitis that typically affects small arteries in the skin, joints, intestinal tract and kidneys. It usually resolves spontaneously but sometimes can cause serious problems in the kidneys and intestinal tract. A 6-year-old girl with purpura, arthralgia and abdominal pain for 2 weeks was admitted. She also showed gross hematuria, generalized edema and decreased urine output. Blood pressure was in the upper normal range. Initial laboratory findings showed hypoalbuminemia, hyperlipidemia, microhematuria and nephrotic-range proteinuria(27.2 g/day). Initially, she was treated with pulse methylprednisolone, azathioprine, albumin and furosemide. Her renal biopsy revealed diffuse mesangial proliferation with strong IgA deposition. There were no crescents. On the third hospital day, she complained of severe abdominal pain and free peritoneal air was seen on abdominal X-ray. Primary repair of small bowel was performed and two pin-point sized holes were found. One week later, she still showed heavy proteinuria. Therefore, we added an ACE inhibitor and dipyridamole, and changed azathioprine to cyclosporine. One month later, the urine protein/creatinine ratio was decreased to 17.8 from 57, but heavy proteinuria has been still persisted. Here we report a rare case of a patient with HSP who had both severe nephrritc-nephrotic syndrome and small bowel perforation.

• Journal of Veterinary Clinics
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• v.29 no.3
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• pp.255-258
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• 2012

A 14-year-old spayed female, Shihtzu dog, presented with anorexia, depression and respiratory distress. She had a history of mastectomy for mammary gland tumor before 2 weeks. Severe gingivitis, dental plaque, and calculus were confirmed on physical examination. On auscultation, the dog had a diastolic and systolic murmur at the left heart base and right heart apex respectively. The dog had valvular vegetation including tricuspid and aortic valves with regurgitation on echocardiography. Blood culture was performed to confirm bacterial endocarditis and identify pathogens of bacterial endocarditis. Before the result of blood culture was confirmed, antibiotic (cefalexin, 30 mg/kg, PO, q12hr) with furosemide (2 mg/kg, PO, q12hr) and benazepril (0.25 mg/kg, PO, q12hr) were administered empirically and the patient was well controlled. Staphylococcus pseudintermedius was confirmed later. One week later, however, the patient died of acute respiratory distress caused by fulminant pulmonary edema. The owners denied necropsy of the patient.

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.265-271
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• 2001

In order to elucidate the influence of intestinal and hepatic first-pass effect on the pharmacokinetics of triflusal, the biotransformation of triflusal in the gastrointestinal tract and liver was designed. Moreover, we tried to establish an HPLC method applicable for bioassay and available to pharmacokinetics, not only with the simultaneous determination of triflusal and its active metabolite, 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), but also with improving sensitivity. After the administration of triflusal (10 mg/kg) and HTB (10 mg/kg) into femoral vein, portal vein (only triflusal) and oral route (only triflusal), pharmacokinetic parameters were investigated from the plasma concentration-time profiles of triflusal and HTB in rats. An HPLC method was developed for the simultaneous determination of triflusal and HTB in rat plasma, urine and bile. The HPLC analysis was carried out using a C18 column and acetonitrile-methanol-water (25:10:65, v/v/v) as the mobile phase and UV detection at 234 nm. Furosemide was used as the internal standard. The calibration curves were linear over the concentration range $0.05-5.0\;{\mu}g/ml$ for triflusal and $0.2-200.0\;{\mu}g/ml$ for HTB with correlation coefficients greater than 0.999 and with intra-day or inter-day coefficients of variation not exceeding 10.0%. This assay procedure was applied to the study of metabolite pharmacokinetics of triflusal and HTB in rats. It was supposed that triflusal was almost metabolized in vivo because urinary and biliary excreted amounts of triflusal could be ignored as it was lower than 1.2% of the administered dose. According to the gastrointestinal and hepatic biotransformation pathways of triflusal, it was found that triflusal was hydrolyzed by about 5% in intestine and metabolized by about 53% in liver, and that the bioavailability of triflusal after oral administration of triflusal was 0.44, and also that the fraction of total elimination rate of triflusal which formed HTB in liver $(F_{mi},\;%)$ was about 98%. These results showed that triflusal was almost metabolized in liver, and the total elimination of triflusal in the body was dependent to the formation rate of HTB from triflusal in liver.

• Tuberculosis and Respiratory Diseases
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• v.59 no.4
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• pp.432-435
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• 2005

An 82-year-old female non-smoker with a history of hypertension presented with increasing dyspnea, cough and some purulent sputum without fever. Upon admission, the patient was in a distressed condition. Auscultation revealed diminished breath sounds with no rales over the right lung. An examination of the heart revealed a regular rhythm and a systolic murmur radiating from the apex of the heart. There was no pitting edema in the lower extremities. The blood tests showed mild leukocytosis and an increased C-reactive protein level. The $O_2$ saturation was 98 % whilst breathing room air. The electrocardiogram demonstrated sinus tachycardia. The chest radiograph showed a moderate cardiomegaly, right lobe infiltrates, and blunting of the both costophrenic sulcus suggesting a small pleural effusion. Three days after admission, the symptoms became slightly aggravated despite being treated with empirical antibiotics for presumed community-acquired pneumonia. Transthoracic color Doppler echocardiography indicated an ejection fraction of 48 %, mild left ventricular enlargement, and moderate left atrial enlargement resulting in severe mitral regurgitation. The clinical symptoms and right pulmonary edema resolved quickly with intravenous furosemide treatment.

• Korean Journal of Clinical Pharmacy
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• v.29 no.3
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• pp.166-172
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• 2019

Background: Hypercalcemia is an important metabolic emergency condition in cancer patients. Bisphosphonate is the treatment of choice for hypercalcemia, whereas calcitonin and hydration with furosemide are recommended for acute supportive therapy. However, data regarding real-world treatment patterns and outcomes of pharmacological treatments are limited. Therefore, we aimed to investigate the treatment patterns and clinical outcomes of hypercalcemia treatment in solid tumor patients. Methods: Electronic medical records of 123 adults with solid cancers and albumin-corrected calcium levels >10.5 mg/dL or ionized calcium levels >1.35 mmol/L were reviewed. We retrospectively analyzed the pharmacological treatment and recovery rate according to the severity of hypercalcemia. Results: A total of 177 cases were identified, of which 49 were not treated and 30 were treated with hydration only. In moderate-to-severe cases, 86.5% received pharmacological treatment. Thirty-four cases (19.2%) were treated with bisphosphonate alone and 58 cases (32.8%) were treated with bisphosphonate and calcitonin. In mild hypercalcemia cases, the recovery rate was higher for those receiving hydration only or pharmacological treatment (79.7%) than for those receiving no treatment (61.4%, p = 0.041). Most moderate-to-severe cases were treated with medication and of those treated, 56.3% recovered. The recovery rate was lower in those treated with bisphosphonate alone (38.2%) than in those who underwent calcitonin combination treatment (73.7%, p = 0.001). Conclusions: Bisphosphonate combined with calcitonin was found to be more effective than bisphosphonate alone for the treatment of moderate-to-severe hypercalcemia. Considering the current shortage of calcitonin, further efforts are required to ensure its stable supply.