• Analytical Science and Technology
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• v.18 no.4
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• pp.271-277
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• 2005

Urea in blood has been measured as an effective marker for diagnosis of renal function. Urea which is e end-product of nitrogen containing metabolites such as proteins is filtered through glomeruli of kidneys and then excreted as urine. If the renal function is deteriorated, the urea concentration in blood will be increased, from which the healthiness of renal function is judged. In order to improve the confidence of diagnosis results, the results must keep traceability chain to certified reference materials, which was certified by primary reference method. In this study, we proposed isotope dilution-liquid chromatography/mass spectrometry (ID-LC/MS) as a candidate primary method, in which $15^N_2$-urea is used as an internal reference material. The developed method is highly accurate in principle and is convenient as it does not require cumbersome derivatization. 0.1 mmol/L ammonium chloride was selected as a mobile phase for HPLC because it provided low interference in MS analysis of relatively low molecular weighted urea. HPLC and MS were connected with an electrospray ionization (ESI) interface of positive mode, which provided high sensitivity and reproducibility. The developed method was validated with internationally recognized reference materials, and we have obtained satisfactory results in an international ring trial. The expanded uncertainty calculated according to ISO guide was 1.8% at 95% confidence interval. The developed method is being used as a primary reference measurement method such as for certification of serum certified reference materials (CRMs).

• 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.

• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.122-132
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• 1998

SB-31 which contains Pursatilla, Licoris and Ginseng extracts was recently proved as an anticancer agent. In a preclinical effort to be applied this drug to human, pharmacokinetics of SB-31 was carried out in rats and rabbits. Glycyrrhizin(GZ), a saponin of Licoris was used as a standard ingradient for the pharmacokinetics of SB-31. The rat's blood, bile and urine samples were serially collected in femoral vein, common bile duct and bladder, respectively, after bolus i.v. injection at a dose of 1 or 1/5 ampul/rat and rabbit's blood samples from the marginal ear vein at a dose of 1 or 3 amp./rabbit. GZ and glycyrrhetic acid(GA), a major metabolite of GZ in the physiological samples were analysed by HPLC with UV detection. The decline of GZ in plasma concentration was generally biexponential at each dose. GZ was almost completely recovered in bile within 18 hour. GA wasn't detected in the samples with UV detector. In the rat, Vss and Kel at a dose of 1 and 1/5 ampul of SB-31 were $98.06\pm6.07\;ml,\;0.33\pm0.05\;hr^{-1}\;and\;65.46\pm11.19\;ml,\;0.68\pm0.25\;hr^{-1}$, respectively. Those in rabbits at a dose of 3 and 1 ampul of SB-31 were $235.24\pm30.72\;ml,\;0.13\pm0.36\;hr^{-1}\;and\;341.32\pm28.58\;ml,\;0.27\pm0.04\;hr^{-1}$, respectively. 'WinNonlin' was utilized for the compartmental analysis. A two-compartment model was chosen as the most appropriate pbarmaco-kinetic model. The data were best described by using a weighting factor of $1/y^2$. To evaluate the effect of SB-31 on cardiovascular system, serially diluted SB-31 was directly injected into coronary artery in the isolated perfused rat heart and the effect of PSF, PSH, saponins of Pursatilla, and SB-31 on PT, APTT of healthy human plasma was examined. Except the positive inotropic effect of ten times diluted solution of SB-31, there was no significant effect on LVDP, (- dp/dt)/(+dp/dt), heart rate and coronary flow in comparision with that of vehicle. SB-31 had no effect on PT but slightly delayed APTT about $6.9{\sim}11.5\%$. There was no significant effect of PSF and PSH on PT & APTT. Conclusively, SB-31 did not show any notable toxic effects on cardiovascular system.

• Journal of Korean Academy of Nursing
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• v.11 no.1
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• pp.19-27
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• 1981

This Study was conducted at Intensive Care Unit of H & S Hospitals from Jan 4 to April 7, 1981 on 14mail & 26female adult patients. Each patient was screened and found to have nonbacteriuria in clean catch specimen before catheterization. Clean catch apecimen through Foley catheter were obtained after 24hours, 48hours and 72hours from catheterization. The result of this study is reviewed in a statistical analysis of percentage ＆ Chi Square test to obtain the following findings. 1) The occurenc of bacteriuria in patients according to duration of indwelling catheter. a. 9.1％ of the patient showed evidence of bacteriuria 24hours post catheterization specimen and 60％ showed 48hours post cathetreization, while 68.4％ of the patient showed evidence of bacteriuria 72hours post catheterization specimen. The occurence of bacteriuria in patients were significant differences at 1％ level between duration of indwelling catheter. b. Mail patients had no infection 24hours post catheterization, 50％ displayed bacteriuria 48hours post catheterization ＆ 62.5％ displayed bacteriuria 71hours post catheterization. 11.1％ of femail patients displayed infection 24hours post catheterization 66.7％ displayed infection 48hours post catheterization and 72.7％ displayed infection 72hours post catheterization. There were significant differences at 1％ level between bacteriuria occurence of mail ＆ femail patients and the duration of insertion. 2) 56％ of those patient who have altered mental state developed bacteriuria, while 40％ of those patient who have alear mental state developed bacteriuria. But there was without statistically any significant difference between patient's mental status. 3) The occurence of bacteriuria with the administration of antibiotics in 36 patient was in 50％. The occurence of bacteriuria without the administration of antibiotics in 4 patients was in 50％. But there was without statistically any significant difference between the administration of antibiotics. 4) The occurence of bacteriuria in patients according to frequency of bladder irrigation. 50％ of those patient who irrigated twice a day developed bacteriuria, 63.6％ of those patient who irrigated once a day developed bacteriuria. The occurence of bacteriuria in patients were significant differences at 1％ level between frequency of bladder irrigation. 5) The occurence of bacteriuria in patients who did perineal care once a day was 58.1％, 22.6％ of those patient who did perineal care twice a day developed bacteriuria. But there was without statistically any signiticant differences between frequency of perineal care. 6) Most frequent bacteria of all bacterial strains isolated by culture of the urine was E. coli(45％). Enterococci & Staphylococcus were 15％ respectively.

• Tuberculosis and Respiratory Diseases
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• v.71 no.1
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• pp.8-14
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• 2011

Background: MicroRNAs (miRNAs) have demonstrated their potential as biomarkers for lung cancer diagnosis. In recent years, miRNAs have been found in body fluids such as serum, plasma, urine and saliva. Circulating miRNAs are highly stable and resistant to RNase activity along with, extreme pH and temperatures in serum and plasma. In this study, we investigated serum miRNA profiles that can be used as a diagnostic biomarker of non-small cell lung cancer (NSCLC). Methods: We compared the expression profile of miRNAs in the plasma of patients diagnosed with lung cancer using an miRNA microarray. The data from this assay were validated by quantitative real-time PCR (qRT-PCR). Results: Six miRNAs were overexpressed and three miRNAs were underexpressed in both tissue and serum from squamous cell carcinoma (SCC) patients. Sixteen miRNAs were overexpressed and twenty two miRNAs were underexpressed in both tissue and serum from adenocarcinoma (AC) patients. Of the four miRNAs chosen for qRT-PCR analysis, the expression of miR-23a was consistent with microarray results from AC patients. Receiver operating characteristic (ROC) curve analyses were done and revealed that the level of serum miR-23a was a potential marker for discriminating AC patients from chronic obstructive pulmonary disease (COPD) patients. Conclusion: Although a small number of patients were examined, the results from our study suggest that serum miR-23a can be used in the diagnosis of AC.

• Journal of Yeungnam Medical Science
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• v.2 no.1
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• pp.229-235
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• 1985

This study was undertaken for the clinical evaluation and statistical analysis on the 88 women with histopathologically confirmed ectopic pregnancies who were admitted and treated from grand opening on May-28, 1983 to Sept.-30, 1985. Incidence of ectopic pregnancy was 1 in 22.2 deliveries and the most common age group was in 30~34 years of age. There was tendency of decreasing incidencies as the gravidity, panty or artificial abortion were over 3. The most common etiologic factor was pelvic inflammatory disease and procedures for family planning were the next common. Common symptoms were lower abdominal pain (85.2%) and vaginal spotting (56.8%). At the admission, hemoglobin level under 10gm% were 44.3%, 69.5% of urine HCG tests were positive. Culdocentesis was positive only in 75.9%. Termination was frequent at 6 ~ 7 weeks of gestation mostly with rupture or abortion. Free blood in the abdominal cavity was averaged 1,224 ml. 4 cases of clinicobiochemically suspected ectopic pregnancies with spontaneous regression were excluded, and there was no fatal case treated in hospital.

• Journal of the Korean Chemical Society
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• v.32 no.4
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• pp.323-332
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• 1988

The bacteria containing urease convert each molecule of urea into two molecules of ammonia and one molecule of carbon dioxide gas. Bacterial electrodes have been constructed by immobilizing the Proteus vulgaris on an ammonia and a carbon dioxide gas-sensors, and were investigated for the effects of pH, temperature, buffer solution, bacterial amounts and interferences, and life time. NH3-bacterial electrode based on ammonia gas-sensor had linearity in the range of $7.0{\times}10^{-4}\;-\;3.0{\times}10^{-2}$M urea in pH 7.4, 0.05M phosphate buffer at $25^{\circ}C$ with a slope of 116.7 mV/decade. While $CO_{2-}$bacterial electrode based on carbon dioxide gas-sensor bad linearity in the range of $7.0{\times}10^{-4}\;-\;5. 0{\times}10^{-2}$M urea in pH 7.0, 0.1M phosphate buffer at $30^{\circ}C$with a slope of $45.4{\times}45.7mV/decade$. As the clinical application, urea in urine was determined by these devices and this result was compared with spectrophotometric method. Consequently, these electrodes could be used for the analysis of many samples because of simplicity, rapidity and convenience of the experimental procedure.

• Journal of Dental Anesthesia and Pain Medicine
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• v.20 no.3
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• pp.129-135
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• 2020

Background: Postoperative fluid retention is a factor that causes delay in recovery and unexpected adverse events. It is important to prevent intraoperative fluid retention, which is putatively caused by intraoperative release of stress hormones, such as ADH (anti-diuretic hormone) or others. We hypothesized that intraoperative analgesia may prevent pathological fluid retention. We retrospectively explored the relationship between analgesics and in-out balance in surgical patients from anesthesia records. Methods: Anesthetic records of 80 patients who had undergone orthognathic surgery were checked in this study. Patients were anesthetized with either TIVA (propofol and remifentanil) or inhalational anesthesia (sevoflurane and remifentanil). During surgery, acetated Ringer's solution was infused for maintenance at a rate of 3-5 ml/kg/h at the discretion of the anesthetist. The perioperative parameters, including the amount of crystalloid and colloid infused, and the amount of urine and bleeding were checked. Furthermore, we checked the amount and administration rate of remifentanil during the surgical procedure. The correlation coefficient between the remifentanil dose and the in-out balance or the urinary output was analyzed using the Pearson correlation coefficient. The contributing factor to fluid retention, including urinary output, was statistically examined by means of multivariate logistic regression analysis. Results: A significant positive correlation was found between remifentanil dose and urinary output. Urinary output less than 0.04 ml/kg/min was suggested to cause positive fluid balance. Although in-out balance approaches zero balance with increase in remifentanil administration rate, no contributing factor for near-zero fluid balance was statistically picked up. The remifentanil administration rate was statistically picked up as the significant factor for higher urinary output (> 0.04 ml/kg/min) (OR, 2,644; 95% CI, 3.2-2.2 × 10⁶) among perioperative parameters. Conclusions: In conclusion, remifentanil contributes in maintaining the urinary output during general anesthesia. Although further prospective study is needed to confirm this hypothesis, it was suggested that fluid retention could be avoided through suppressing intraoperative stress response by means of appropriate maintenance of remifentanil infusion rate.

• Journal of Pharmacopuncture
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• v.7 no.1 s.12
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• pp.37-51
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• 2004

Objective : Recently scolopendrid aqua-acupuncture has been a good effect on pain control but it has not been known about clinical safety. The purpose of this study was to investigate acute toxicity of scolopendrid aqua-acupuncture. Method : In order to prove the clinical safety of scolopendrid aqua-acupuncture, We have observed a bacteriological examination and clinical pathology test after scolopendrid aqua-acupuncture treatment. Balb/c mice were injected intravenous with Scolopendrid aquaacupuncture treatment for $LD_{50}$ and acute toxicity test. We analyzed physical reaction(side effect)and clinical pathology test before and after Scolopendrid aqua-acupuncture treatment of mice and 20 patients suffering from pain, who admitted department of Acupunture and Moxibustion, College of Oriental Medicine, Won-Kwang University Kwangju hospital. Results : In the Blood agar plate and Nutrient agar plate, a bacteriological examination did not show a bacillus. In acute $LD_{50}$ toxicity test, there was no mortality thus unable to attain the value. Examining the toxic response in the acute toxicity test, there was no sign of toxication. In acute toxic test, running biochemical serum test couldn't yield any differences between the control and experiment groups. In the 20 patients treated with Scolopendrid aqua-acupuncture, hematologic test did not show remarkable change. In the 20 patients treated with Scolopendrid aqua-acupuncture, Liver function test(AST, ALT, ALP) showed a slight decrease on the contrary, and abnormal rate showed a decrease of 5.0% compared with previous study. Reanl function test(BUN, Cr) and abnormal rate showed a decrease of 5.0% compared with previous study. In the 20 patients treated with Scolopendrid aqua-acupuncture, Electrolyte were normal range before and after treatment. In the Urine analysis of 20 patients, Leukocyte, Protein, Glucose, Keton, Bilirubin, U-bilinogen were not detected before and after Scolopendrid aqua-acupuncture treatment, and the rest almost made no difference.

• 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 $0.038{\pm}0.034$.