• Archives of Pharmacal Research
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• v.26 no.7
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• pp.564-568
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• 2003

Pharmacokinetic and pharmacodynamic properties of gliclazide were studied after an oral administration of gliclazide tablets in healthy volunteers. After an overnight fasting, gliclazide tablet was orally administered to 11 volunteers; Additional 10 volunteers were used as a control group (i.e., no gliclazide administration). Blood samples were collected, and the concentration determined for gliclazide and glucose up to 24 after the administration. Standard pharmacokinetic analysis was carried out for gliclazide. Pharmacodynamic activity of the drug was expressed by increase of glucose concentration ($\Delta$PG), by area under the increase of glucose concentration-time curve ($AUC_{$\Delta$PG}$) or by the difference in increase of glucose concentration ($D_{$\Delta$PG}$) at each time between groups with and without gliclazide administration. Pharmacokinetic analysis revealed that $C_{max}, T_{max}$, CL/F (apparent clearance), V/F (apparent volume of distribution) and half-life of gliclazide were $4.69\pm1.38 mg/L, 3.45\pm1.11 h, 1.26\pm0.35 L/h, 17.78\pm5.27 L, and 9.99\pm2.15 h$, respectively. When compared with the no drug administration group, gliclazide decreased significantly the $AUC_{$\Delta$PG}$ s at 1, 1.5, 2, 2.5, 3 and 4 h (p＜0.05). The $\Delta$PGs were positively correlated with $AUC_{gliclazide}$ at 1 and 1.5 h (p＜0.05), and the correlation coefficient was maximum at 1 h (r = 0.642) and gradually decreased at 4 h after the administration. The $AUC_{$\Delta$PG}$s were positively correlated with $AUC_{gliclazide}$ at 1, 2, 3 and 4 h (p＜0.05), and the maximum correlation coefficient was obtained at 2 h (r=0.642) after the administration. The $D_{$\Delta$PG}$ reached the maximum at 1 h, remained constant from 1 h to 3 h, and decreased afterwards. Therefore, these observations indicated that maximum hypoglycemic effect of gliclazide was reached at approximately at 1.5 h after the administration and the effect decreased, probably because of the homeostasis mechanism, in health volunteers.

• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.170-172
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• 2013

The pyrimidine nucleoside uridine has recently been reported to have a protective effect on cultured human corneal epithelial cells, in an animal model of dry eye and in patients. In this study, we investigate the pharmacokinetic profile of uridine in rabbits, following topical ocular (8 mg/eye), oral (450 mg/kg) and intravenous (100 mg/kg) administration. Blood and urine samples were serially taken, and uridine was measured by high-performance liquid chromatography-tandem mass spectrometry. No symptoms were noted in the animals after uridine treatment. Uridine was not detected in either plasma or urine after topical ocular administration, indicating no systemic exposure to uridine with this treatment route. Following a single intravenous dose, the plasma concentration of uridine showed a bi-exponential decay, with a rapid decline over 10 min, followed by a slow decay with a terminal half-life of $0.36{\pm}0.05$ h. Clearance and volume of distribution were $1.8{\pm}0.6$ L/h/kg and $0.58{\pm}0.32$ L/kg, respectively. The area under the plasma concentration-time curves (AUC) was $59.7{\pm}18.2{\mu}g{\cdot}hr/ml$, and urinary excretion up to 12 hr was ~7.7% of the dose. Plasma uridine reached a peak of $25.8{\pm}4.1{\mu}g/ml$ at $2.3{\pm}0.8$ hr after oral administration. The AUC was $79.0{\pm}13.9{\mu}g{\cdot}hr/ml$, representing ~29.4% of absolute bioavailability. About 1% of the oral dose was excreted in the urine. These results should prove useful in the design of future clinical and nonclinical studies conducted with uridine.

• Genomics & Informatics
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• v.14 no.4
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• pp.181-186
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• 2016

Glucose tolerance tests have been devised to determine the speed of blood glucose clearance. Diabetes is often tested with the standard oral glucose tolerance test (OGTT), along with fasting glucose level. However, no single test may be sufficient for the diagnosis, and the World Health Organization (WHO)/International Diabetes Federation (IDF) has suggested composite criteria. Accordingly, a single multi-class trait was constructed with three of the fasting phenotypes and 1- and 2-hour OGTT phenotypes from the Korean Association Resource (KARE) project, and the genetic association was investigated. All of the 18 possible combinations made out of the 3 sets of classification for the individual phenotypes were taken into our analysis. These were possible due to a method that was recently developed by us for estimating genomic associations using a generalized index of dissimilarity. Eight single-nucleotide polymorphisms (SNPs) that were found to have the strongest main effect are reported with the corresponding genes. Four of them conform to previous reports, located in the CDKAL1 gene, while the other 4 SNPs are new findings. Two-order interacting SNP pairs of are also presented. One pair (rs2328549 and rs6486740) has a prominent association, where the two single-nucleotide polymorphism locations are CDKAL1 and GLT1D1. The latter has not been found to have a strong main effect. New findings may result from the proper construction and analysis of a composite trait.

• Korean Journal of Clinical Pharmacy
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• v.11 no.1
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• pp.1-6
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• 2001

This research is conducted to evaluate the clinical and economic benefits from therapeutic drug monitoring(TDM) service on vancomycin in a tertiary general hospital. Total 99 pairs of steady state peak and trough concentrations of vancomycin were obtained from 73 patients. To see the clinical benefits, the appropriateness of vancomycin dosing before TDM was evaluated. In 72 pairs of vancomycin blood concentrations obtained prior to TDM consultation, $47.2\%$ of the cases had reached within therapeutic range. Serum vancomycin levels in patients with $40{\leq}CLcr<60$ (ml/min) were higher and than the levels in patients with 40>CLcr and $60{\leq}CLcr$ (ml/min). Dose reduction rate in patients with creatinine clearance $40{\leq}CLcr<60$ (ml/min) were also significantly higher than those of compared groups ($61.5\%$, p=0.0138). Serum vancomycin concentrations were re-obtained from 21 patients who received modified dose through TDM service. Ninety percent (19/21cases) of them were within the target therapeutic range. For the evaluation of economic benefits from TDM consultation, estimated cost savings were calculated in those patients. The total drug saving were 586 vials in 21 patients. The calculated mean cost saving from the drugs was 314,570 won (range: $11,273\sim473,466)$ per patient. The study revealed that TDM service for vancomycin is necessary because empirical dosing is not effective for obtaining therapeutic drug level, especially patients with mild renal insufficiencies. The cost saving from TDM is also beneficial for the patients.

• The Korean Journal of Nuclear Medicine
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• v.8 no.1_2
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• pp.13-24
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• 1974

The patterns of renogram in patients with Korean hemorrhagic fever were evaluated with clinical course and renal hemodynamic changes in various clinical stages. The renal plasma flow was measured by hippuran blood clearance using $^{131}I$-ortho-iodohippurate and hippuran renogram was analysed by means of quantitative and qualitative methods in 26 patients of Korean hemorr hagic fever. The results obtained with this study were as follows; 1. During the oliguric phase of Korean hemorrhagic fever, the renogram showed non-functioning (flat) or obstructive pattern. The group of patients with non-functioning pattern of renogram had more severe impairement of renal function and grave prognosis than the group with obstructive pattern of renogram. 2. During the diuretic phase, the renogram showed obstructive or dysfunction or normal pattern, which was related with the recovery of renal function. Obstruction pattern of renogram was observed till the 2nd week of diuretic phase. Normal pattern of renogram began to appear by the 2nd week of diuretic phase. 3. During the convalescent phase of Korean hemorrhagic fever, 40% of patients showed dysfunnction pattern of renogram, and the recovery of abnormal renogram in Korean hemorrhagic fever was more delayed than the recovery of clinical features and laboratory findings. 4. The renogram showed normal pattern 6 months after onset of Korean hemorrhagic fever in all cases. 5. There was significant correlationship between the pattern of renogram and the decreace of renal plasma flow in the patients with Korean hemorrhagic fever. The decreace of renal plasma flow was maked in the patients with non-functioning pattern of renogram and was least in the patients with dysfunction pattern of renogram. All above results suggested that the renogram reflects the effective renal plasma flow and degree of renal impairement, and the renogram may be one of the important indexes which could give us a more precise prognosis in Korean hemorrhagic fever.

• Transactions of the Korean Society of Mechanical Engineers A
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• v.34 no.12
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• pp.1893-1899
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• 2010

A foxtail moves forward on a flat surface when pushed by a vertical force. The distance moved by the foxtail depends on the degree of deformation. We experimentally investigated the main parameters that influence the distance moved while varying the pushing force, area, and velocity. We then fabricated a nylon barb that mimics the foxtail barb and performed theoretical and experimental analyses of the displacement according to the acting force and the deflection. In addition, we investigated the relation between the displacement and the angle of a foxtail-like robot's leg by varying the clearance between the robot body and the inner surface of the pipe. To find the design parameters of the barb of the robot for tubular-type digestive organs and blood vessels, we studied the relation between the acting force and the elastic modulus while varying the leg diameter.

• The Korean Journal of Pharmacology
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• v.12 no.2 s.20
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• pp.43-49
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• 1976

The facts that $PGE_2$ produced diuresis in the rabbit when given into a lateral ventricle of the brain and that $PGF_{2{\alpha}}$ is abundantly found in the brain prompted us to investigate the effects of $PGF_{2{\alpha}}$ introduced directly into the ventricle on the renal function. $PGF_{2{\alpha}}$ given intraventriculary in doses of $10{\mu}g\;and\;100{\mu}g$ elicited prompt diuresis, 10-fold increase of sodium excretion and two-fold increment of potassium excretion. Free water reabsorption also increased along with the increased osmolar clearance. Neither renal plasma flow nor glomerular filtration rate did change significantly. This, along with the fact that the percentage of reabsorbed sodium filtered decreased from 99.5 to 93.9, indicates the tubular site of the diuretic and natriuretic action. Atropine pretreatment did not influence the renal effects of intraventricular $PGF_{2{\alpha}}$. Intravenously administered $PGF_{2{\alpha}}$ in doses of 30 to $100{\mu}g$ did not produce any significant change in renal function. Intraventricular $PGF_{2{\alpha}}$ had no effect on the systemic blood pressure, whereas intravenous administration brought about a transient hypotension. These observations suggest that $PGF_{2{\alpha}}$ induces diuresis and natriuresis via central mechanism, that the site of the action resides in renal tubules, and that the reabsorption of sodium is inhibited in the proximal tubule, possibly through mediation of certain humoral agent. Overall, it is suggested that $PGF_{2{\alpha}}$ might play a roll in regulating renal function through the center.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.6
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• pp.637-647
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• 2018

Extra-hypothalamic growth hormone-releasing hormone (GHRH) plays an important role in reproduction. To study the treatment effect of Grin (a novel hGHRH homodimer), the infertility models of 85 male Chinese hamsters were established by intraperitoneally injecting 20 mg/kg of cyclophosphamide once in a week for 5 weeks and the treatment with Grin or human menopausal gonadotropin (hMG) as positive control was evaluated by performing a 3-week mating experiment. 2-8 mg/kg of Grin and 200 U/kg of hMG showed similar effect and different pathological characteristics. Compared to the single cyclophosphamide group (0%), the pregnancy rates (H-, M-, L-Grin 26.7, 30.8, 31.3%, and hMG 31.3%) showed significant difference, but there was no difference between the hMG and Grin groups. The single cyclophosphamide group presented loose tubules with pathologic vacuoles and significant TUNEL positive cells. Grin induced less weight of body or testis, compactly aligned tubules with little intra-lumens, whereas hMG caused more weight of body or testis, enlarging tubules with annular clearance. Grin presented a dose-dependent manner or cell differentiation-dependentincrease in testicular GHRH receptor, and did not impact the levels of blood and testicular GH, testosterone. Grin promotes fertility by proliferating and differentiating primitive cells through up-regulating testicular GHRH receptor without triggering GH secretion, which might solve the etiology of oligoasthenozoospermia.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4899-4906
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• 2016

Aim: To assess the diagnostic utility of serum and salivary interleukin 6 (IL-6) levels in the differential diagnosis of potentially malignant lesions and conditions (PMLs/PMCs) and oral squamous cell carcinoma (OSCC) in a high oral cancer prevalence region. Methods: After appropriate ethical clearance and informed consent, salivary and blood samples were collected from 100 participants in each group (OSCC, PMLs, and healthy controls). Serum and salivary IL-6 levels were measured by enzyme-linked immunosorbent assay and data were subjected to appropriate statistical analysis. Results: Significant differences in IL-6 concentration were noted between OSCC and PML/C patients in both serum and saliva, with salivary levels being 2 to 3 fold higher than serum values in all the groups. Receiver operating characteristic curve analysis demonstrated 96% specificity and 99% sensitivity for salivary IL-6 in differentiating PML from OSCC. Conclusions: The results of the present study suggest that the pro-inflammatory cytokine, IL-6, is elevated in the saliva of patients with OSSC compared to PMD and controls, and thus may prove to have diagnostic and/or prognostic significance.

• Korean Journal of Bronchoesophagology
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• v.15 no.2
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• pp.36-41
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• 2009

Background : Controversy exists whether patients with esophageal carcinoma are best managed with classical Ivor Lewis esophagectomy(ILO) as combined thoracic and abdominal approach or transhiatal esophagectomy(THO). The THO approach is known to be superior with respect to operative time, morbidity and mortality, and length of stay, especially at poor pulmonary function patient, but may represent an inferior cancer operation due to inadequate mediastinal clearance compared with ILO. Accordingly, we estimated the THO role at esophageal cancer to compare each operative approach. Material and Method : From January 2002 to December 2007, we performed a retrospective review of all esophagectomies performed at Keimyung University Dongsan Medical Center; 36 underwent THO, and 11 underwent ILO. Result : There were all men and squamous cell carcinoma but 1 woman at ILO group, 2 women at THO group. There were no significant differences between THO and ILO with age, sex, location of tumor, mean tumor length. There were significant differences at preoperative pulmonary function test(In ILO group, average FEV1 is $2.65{\pm}0.6\;L/min$ and iIn THO group, average FEV1 is $2.07{\pm}0.7\;L/min$). The amount of blood transfusion, hospital stay, leak rates and respiratory complication, hospital mortality rate were not significantly different. Conclusion : There was no significant difference in the post-operative complication, hospital mortality rate, long-term survival of patients of both operative method. THO method had lower mobidity and mortality at poor pulmonary function patient than ILO method. Hence, THO is a valid alternative to ILO for patients with poor general condition or expected post-operative respiratory complication.