• YAKHAK HOEJI
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• v.39 no.2
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• pp.103-112
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• 1995

Population pharmacokinetics for gentamicin were compared with 24 American patients (16 male and 8 female) and 16 Korean-American appendicitis patients(12 male and 4 female). Two to six blood specimens were collected from all patients at the following times: just before a regularly scheduled infusion and at 1/2 hour after the end of a 1/2 hour infusion. Nonparametric expected maximum(NPEM) algorithm for population modeling was used. The estimated parameters were the elimination rate constant(K), the slope of the relationship between K versus creatinine clearance(KS), the apparent volume of distribution(V), the slope of the relationship between V versus weight(VS), gentamicin clearance(CL) and the slope of the relationship between CL versus creatinine clearance and the VS(CS). The output includes a 3-dimensional plot of the joint probability density function(PDF), two marginal PDF, means, medians, modes, variance, skewness, kurtosis, and CV%. The mean K(KS) were 0.424$\pm$0.139(0.00429$\pm$0.00164) and 0.411$\pm$0.135 hr$^{-1}$ (0.00475$\pm$0.00180[hr.mL/min/1.73m$^{2}]^{-1}$) for American and Korean-American populations, respectively. The mean V(VS) were not different at 15.6$\pm$4.77(0.233$\pm$0.0526) and 15.1$\pm$3.84L(0.239$\pm$0.0492 L/kg) for American and Korean-American populations, respectively (P>0.2). The mean CL (CS) were 6.28$\pm$1.85(0.0634$\pm$0.0191) and 5.70$\pm$1.77 L/hr(0.0701$\pm$0.0215 L/kg[hr.mL/min/1.73m$^{2}$)] for American and Korean-American populations, respectively. There are no differences in gentamicin pharmacokinetics between American and Korean-American Appendicitis patients.

• YAKHAK HOEJI
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• v.44 no.3
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• pp.245-250
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• 2000

Because nonsteroidal anti-inflammatory drugs are reported to cause fluid retention and hypertension by inhibition of prostaglandin synthesis, the effects of piroxicam on pharmacodynamics and pharmacokinetics of nifedipine were studied in male spontaneously hypertensive rats. They received nifedipine (0.5 mg/kg) alone or combined with piroxicam (5 mg/kg) intravenously. Plasma levels norepinephrine, an index of sympathetic stimulation, were measured prior to each treatment and 5 min after drug administration. Changes in blood pressure were examined serially and blood samples for analysis of nifedipine were also taken for 6 hr following drug administration. Plasma nifedipine concentration were assayed by HPLC and pharmacokinetic parameters were calculated. Blood pressure was reduced (p<0.01), but plasma norepinephrine level was increased (p<0.05) by nifedipine administration. Anti-hypertensive effect of nifedipine was potentiated (p<0.05) by piroxicam coadministration, but effect of nifedipine on plasma norepinephrine level was not affected. In case of rats received nifedipine and piroxicam, plasma nifedipine concentrations were higher (p<0.05) than those from rats received nifedipine alone at 2,3,4,5 and 6 hours following drug administration. The area under the plasma concentration vs. time curve was increased (p<0.05), while the elimination rate constant was decreased (p<0.01) by piroxicam coadministration. No significant differences were observed in the plasma clearance, apparent volume of distribution and elimination half-life. Thus, piroxicam not only potentiated antihypertensive effect of nifedipine, but also altered nifedipine pharmacokinetics in the rats. It is concluded that the potentiation of nifedipine antihypertensive effect might correlate with the increment of its plasma concentration by piroxicam coadministration.

• Journal of Korean Neurosurgical Society
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• v.62 no.1
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• pp.10-26
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• 2019

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer's disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.4
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• pp.211-217
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• 2006

Purpose: Recombinant ScFv lym-1 was produced, using pET vector system for large scale production. Methods: ScFv lym-1 gene inserted pET-22b (+) vector, was expressed in E.coli BL-21 strain. ScFv lym-1 antibody extracted from periplasm, was purified with His-Taq column. To evaluated immunoreactivity with Raji cell, ScFv lym-1 was labeled with I-125 and I-125 ScFv lym-1 was purified with desalting column. Raji cell was injected into the C57BR/cdJ SCID mice. Gamma camera imaging were taken time point at 1, 8, 24, and 48 hr with 8 mm pinhole collimator. Results: An active scFv lym-1 could be produced in E. coli with soluble iron using PET vector system. Immuuoreaetivity and affinity constant of IgG lym-1 were 54% and $1.83{\times}10^9M^{-1}$, respectively, and those of scFv lym-1 were 53.7% and $1.46{\times}10^9M^{-1}$, respectively. Biodistribution of I-125 scFv lym-1 antibody showed faster clearance in blood, spleen, kidney and than I-125 IgG lym-1 antibody. Gamma camera image of I-125 scFv lym-1 antibody showed faster clearance and tumor targeting liver than I-125 IgG lym-1 antibody. Conclusions: In vitro properties of scFv lym-1 were similar to those of IgG lym-1. ScFv lym-1 showed faster blood clearance than IgG lym-1 There results suggest that scFv lym-1 antibody can be useful for tumor imaging agent.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.251-259
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• 1995

Pharmacokinetics and pharmacodynamics of metoprolol, a selective beta-l blocker, were examined for 360 minutes after intravenous bolus administration of metoprolol to 6 dogs. Plasma concentration and excreted amount in the urine metoprolol were measured by liquid chromatography with fluorescence detection. PR interval and heart rate were measured by ECG monitoring. Blood pressure was monitored through intraarterial catheter in femoral artery and cardiac output by thermodilution method using Swan-Ganz catheter. To analyze the effect site concentration-response relationship, plasma concentration and pharmacological effects were simultaneously fitted to a two pharmacokinetic compartment linked to pharmacodynamic model with NONLIN program. Results are as follows. 1) The plasma concentration of metoprolol after intrvenous injection decreased biexponentially. The terminal half-life estimated was $1.33{\pm}0.40$ hours and the volume of distribution at steady state (Vdss) and the total body clearance were $1.04{\pm}0.4\;L/kg,\;6.55{\pm}2.21\;L/hr$, respectively. The central compartment volume of distribution and peripheral compartment volume of distribution were $0.35{\pm}0.14L/kg\;and\;0.69{\pm}0.34L/kg$. The renal clearance and intercompartment clearance were $0.53{\pm}0.25\;L/min\;and\;0.35{\pm}0.19\;L/min$. 2) Simulated biophase concentration-response curve shows hyperbolic relationship and the estimated concentration-effect relationship was best explained by Emax model when the prolongation of PR interval and the reduction of the heart rate were used as pharmacodynamic parameters. Emax and EC50 were estimated to be $26.3{\pm}4.7\;msec\;and\;88.8{\pm}82.3\;g/ml$ for PR interval, and $48.7{\pm}18.8\;beats/min\;and\;113.5{\pm}78.7\;ng/ml$ for heart rate, respectively. 3) The changes of cardiac output-effect site concentration relationship was best fitted by a linear model and the slope of the relationship was $0.005{\pm}0.003$. Diastolic blood pressure-effect site concentration relationship was also explained by the linear model and the slope of the relationship was $0.038{\pm}0.034$.

• Nuclear Engineering and Technology
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• v.55 no.10
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• pp.3815-3821
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• 2023

Dosimetric studies in Nuclear Medicine are very important, especially with new therapeutic methods, the number of which has increased significantly with the Theranostic approach (determining diagnostic-therapeutic pairs where similar molecules are labelled with different isotopes in order to diagnose and treat malignant diseases). Peptide receptor radionuclide therapy (PRRT) has been used successfully for many years to treat neuroendocrine tumors (NET). ⁹⁰Y-DOTATOC is one of the radiopharmaceuticals used frequently in this type of therapy. In this work, blood and urine samples from 13 patients treated with ⁹⁰Y-DOTATOC were measured by a liquid scintillation beta counter (LSC). Calibration of the beta counter for this type of measurement was done and all results are presented in the paper. The presented paper also provides a methodology for determining the measurement uncertainty for this type of measurement. Immediately after the administration of radiopharmaceuticals, the activity in the blood was different from 6.31% to 88.9% of the applied radioactivity, while 3 h after the termination of the application, the average value of radiopharmaceuticals in the blood was only 3.84%. The activity in the excreted urine depended on the time when the patients urinated after the therapy. It was measured that as much as 58% of the applied radioactivity was excreted in the first urine after the therapy in a patient who urinated 4.5 h after the completed application of the therapy. In most patients, the highest urine activity was in the first 10 h after the application, while the activities after that time were negligibly low. The described methodology of measuring and evaluating activity in blood and excreted urine can be applied to other radiopharmaceuticals used in nuclear medicine. It could be useful for researchers for dosimetric assessments in clinical application of PRRT.

• Journal of Korean Academy of Nursing
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• v.23 no.4
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• pp.569-584
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• 1993

This study was done to verify validity of nursing diagnoses related to difficulty in respiratory function. First, content validity was examined by an expert group considering the etiology and the signs / symptoms of three nursing diagnoses - ineffective airway clearance, ineffective breathing pattern, impaired gas exchange. Second, clinical validity was examined by comparing the frequencies of the etiologies and signs / symptoms of the three nursing diagnoses in clinical case studies with the results of the content validity. This study was a descriptive study. The sample consisted of 23 experts (professors, head nurses and clinical instructors) who had had a variety of experiences using nursing diagnoses in clinical practice, and 102 case reports done by senior student nurses of the college of nursing of Y-university. These reports were part of their clinical practice in the ICU. The instrument used for this study was a checklist for etiologies and signs and symptoms based on the literature, Doenges and Moorhouse (1988), Kim, McFarland, McLane (1991), Lee Won Hee et al. (1987), Kim Cho Ja et at. (1988). The data was collected over four month period from May 1992 to Aug. 1992. Data were analyzed using frequencies done with the SPSS / PC＋ package. The results of this study are summarized as follows : 1. General Characteristics of the Expert Group A bachelor degree was held by 43.5% and a master or doctoral degree by 56.5% of the expert group. The average age of the expert group was 35.3 years. Their average clinical experience was 9.3 years and their average experience in clinical practice was 5.9 years. The general characteristics of the patients showed that there were more women than men, that the age range was from 1 to over 80. Most of their medical diagnoses were diagnoses related to the respiratory. system, circulation or neurologic system, and 50% or more of them had a ventilator with intubation or a tracheostomy. The number of cases for each nursing diagnoses was : · Ineffective airway clearance, 92 cases. · Ineffective breathing pattern, 18 cases. · Impaired gas exchange, 22 cases. 2. The opinion of the expert group as to the classification of the etiology, and signs and symptoms of the three nursing diagnoses was as follows : · In 31.8% of the cases the classification of etiology was clear. · In 22.7%, the classification of signs and symptoms was clear. · In 17.4%, the classification of nursing interventions was clear. 3. In the expert group 80% or mere agreed to ‘dysp-nea’as a common sign and symptom of the three nursing diagnoses. The distinguishing signs and symptoms of (Ineffective airway clearance) were ‘sputum’, ‘cough’, ‘abnormal respiratory sounds : rales’. The distinguishing sings and symptoms of (Ineffective breathing pattern) were ‘tachypnea’, ‘use of accessory muscle of respiration’, ‘orthopnea’ and for (Impaired gas exchange) it was ‘abnormal arterial blood gas’, 4. The distribution of etiology, and signs and symptoms of the three nursing diagnoses was as follows : · There was a high frequency of ‘increased secretion from the bronchus and trachea’ in both the expert group and the case reports as the etiology of ineffective airway clearance. · For the etiologies for ineffective breathing pat-tern, ‘rain’, ‘anxiety’, ‘fear’, ‘obstructions of the tract, ca and bronchus’ had a high ratio in the ex-pert group and ‘decreased expansion of lung’ in the case reports. · For the etiologies for impaired gas exchanges, ‘altered oxygen -carrying capacity of the blood’ and ‘excess accumulation of interstitial fluid in lung’ had a high ratio in the expert group and ‘altered oxygen supply’ in the case reports. · For signs and symptoms for ineffective airway clearance, ‘dyspnea’, ‘altered amount and character of sputum’ were included by 100% of the expert group. ‘Abnormal respiratory. sound(rate, rhonchi)’ were included by a high ratio of the expert group. · For the signs and symptoms for ineffective breathing pattern. ‘dyspnea’, ‘shortness of breath’ were included by 100% of the expert group. In the case reports, ‘dyspnea’ and ‘tachypnea’ were reported as signs and symptoms. · For the sign and symptoms for impaired gas exchange, ‘hypoxia’ and ‘cyanosis’ had a high ratio in the expert group. In the case report, ‘hypercapnia’, ‘hypoxia’ and ‘inability to remove secretions’ were reported as signs and symptoms. In summary, the similarity of the etiologies and signs and symptoms of the three nursing diagnoses related to difficulty in respiratory function makes it difficult to distinguish among them But the clinical validity of three nursing diagnoses was established through this study, and at last one sign and symp-tom was defined for each diagnosis.

• Journal of Pharmaceutical Investigation
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• v.9 no.2
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• pp.11-21
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• 1979

It has been reported from our department that a few agents, such as $K_2S_2O_5,\;NaHSO_3,$ nicotinamide have a marked stabilizing effect in vitro on metoclopramide which is relatively unstable compound. In order to study the effect of these stabilizers on the action of metoclopramide in vitro, the fate of this compound combined with $K_2S_2O_5,\;NaHSO_3$ and nicotinamide, respectively, was studied and furthermore, the change of the biological activity of metoclopramide due to these stabilizers was studied by using the isolated stomach strip of rat. The blood concentration of metoclopramide was measured by using Bakke's method at the various time after intravenous injection of the mixed metoclopramide solution with the stabilizers. In order to study the excretion of the drug, rabbits were anesthesized and catheterized into bladder for withdrawal of urine. After intravenous injection of the mixed metoclopramide solution, urine was collected for 5 hours and the conjugated forms of metoclopramide as well as the free form were determined by using Arita's method. In the biological study of the metoclopramide combined with stabilizers, the contractability of the isolated rat stomach strip was observed by using polygraph recorder. The results were following: 1. When metoclopramide was administered with nicotinamide as stabilizer, the blood concentration of the unchanged from and the rate of the clearance of this compound were very similar to that of metoclopramide alone. On the other hand, other stabilizers, $K_2S_2O_5\;and\;NaHSO_3$, brought about 40% decrease in blood concentration of the unchanged form at 15 min after intravenous injection however, the rate of clearance of metoclopramide with $K_2S_2O_5\;or\;NaHSO_3$ was very slow. 2. In the case of urinary excretion, the excretory pattern of the metabolites of metoclopramide with $NaHSO_3$ or nicotinamide was very similar to that of metoclopramide alone. But metodopramide plus $K_2S_2O_5$ group showed the maked depression of excretion for first 1 hour. 3. In composition of metabolites, when metoclopramide was administered with $K_2S_2O_5$ or $NaHSO_3$, the sulfonate conjugation was predominant. But the glucuronic acid conjugation was predominant in metoclopramide plus nicotinamide gronp. 4. In the experiments on the biological activity of the metoclopramide, this compound exhibited the marked contracting effect in isolatd rat stomach strip. Specially, the meetoclopramide combined with $K_2S_2O_5$ showed the strong contraction of the isolated strip, suggesting the potenciating effect of $K_2S_2O_5$ on the action of metoclopramide in the isolated strip.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.359-364
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• 2002

The present study examined the effects of water extract of Hwangruynhaedoktang plus Yukmijihwangtang add Chogudeung (HYC) on the blood pressure and renal function in spontaneously hypertensive rats (SHR). The HYC water extract blocked increase of systolic blood pressure (SBP) in SHR. The urinary volume (UV), sodium (UNaV), potassium (UkV), and chloride (UclV) excretions were significantly increased in SHR administered with high dose of water extract of HYC, but urinary osmolality was not changed. The creatinine clearance (Ccr), which is index of glomerular filtration rate (GFR), was increased by administration of HYC, while solute-free water reabsorption (TcH2O) was not changed. Taken together, these results suggest that the depressor effects of HYC, at least in part, caused by diuretic effect due to increase of glomerular filtration rate.

• 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.