• The Korean Journal of Applied Statistics
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• v.31 no.1
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• pp.123-137
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• 2018

A nonlinear mixed effects model is mainly used to analyze repeated measurement data in various fields. A nonlinear mixed effects model consists of two stages: the first-stage individual-level model considers intra-individual variation and the second-stage population model considers inter-individual variation. The individual-level model, which is the first stage of the nonlinear mixed effects model, estimates the parameters of the nonlinear regression model. It is the same as the general nonlinear regression model, and usually estimates parameters using the least squares estimation method. However, the least squares estimation method may have a problem that the estimated value of the parameters and standard errors become extremely large if the assumed nonlinear function is not explicitly revealed by the data. In this paper, a new estimation method is proposed to solve this problem by introducing the ridge regression method recently proposed in the nonlinear regression model into the first-stage individual-level model of the nonlinear mixed effects model. The performance of the proposed estimator is compared with the performance with the standard estimator through a simulation study. The proposed methodology is also illustrated using quantitative high throughput screening data obtained from the US National Toxicology Program.

• Korean Journal of Veterinary Research
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• v.43 no.3
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• pp.339-347
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• 2003

The regional distribution and relative frequency of some endocrine cells in the pancreas of the Korean aucha perch, Coreoperca herzi Herzenstein belonging to the family Serranidae in order Perciformis, were observed using specific mammalian antisera against serotonin, insulin, glucagon, somatostatin and human pancreatic polypeptide (hPP) by peroxidase antiperoxidase (PAP) method. The pancreas was divided into four portions (principal and secondary islets, exocrine and pancreatic duct regions). In addition, the pancreatic islet regions were further subdivided into three regions (central, mantle and peripheral regions). Spherical to spindle or occasionally round to oval immunoreactive (IR) cells were demonstrated in the pancreatic islets and exoccrine portions, but no cells were detected in the pancreatic duct portions. In the principal islets, serotonin-IR cells were not detected but most of insulin-IR cells were located in the central regions and they were also demonstrated in the mantle and peripheral regions in moderate and rare frequencies, respectively. Glucagon- and hPP-IR cells were mainly situated in the mantle regions but the cells were also demonstrated in the peripheral regions in relatively lower frequency. Somatostatin-IR cells were evenly distributed in the central and mantle regions in a few frequency and cells were also demonstrated in the peripheral regions in rare frequency. Cell clusters were consisted of hPP-IR cells that were situated in the peripheral to mantle regions. In the secondary islet portions, serotonin-IR cells were randomly distributed throughout the whole pancreatic islet regions but lower frequency was detected in the peripheral regions compared to that in central and mantle regions where cells were detected in a few frequency, respectively. Insulin-IR cells were restricted to the central regions in numerous frequency and glucagon-IR cells were evenly distributed in the mantle and peripheral regions in moderate frequencies, respectively. Somatostatin-IR cells were observed in the central and mantle regions in moderate and a few frequencies, respectively. In addition, hPP-IR cells showed similar distributional patterns to those of glucagon-IR cells except cells were also located in the central regions in rare frequency. In the exocrine portions, only glucagon- and hPP-IR cells were demonstrated in rare and a few frequencies, respectively. In conclusion, the regional distribution and relative frequency of pancreatic endocrine cells of the Korean aucha perch showed general patterns, which were observed in other teleost. However, some species-dependent different distributional patterns and/or relative frequencies were also demonstrated especially to serotonin-IR cells. In pancreas of the Korean aucha perch, insulin-IR cells were the most predominant cell type followed by glucagon-, somatostatin-, hPP- and serotonin-IR cells.

• Journal of Pharmaceutical Investigation
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• v.36 no.6
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• pp.405-411
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• 2006

Epinastine is an antiallergic drug effective for bronchial asthma, allergic rhinitis, urticaria and dermatitis. Epinastine is topically active, direct H1-receptor antagonist and an inhibitor of the release of histamine from the mast cell. The purpose of the present study was to evaluate the bioequivalence of two epinastine hydrochloride tablets, Alesion Tablet (Boehringer Ingelheim Korea Ltd.) and S-napine tablet 10 mg(Sam Chun Dang Pharm. Co., Ltd), according to the guidelines of the Korea Food and Drug Administration(KFDA). The release of epinastine from the two epinastine formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media(pH 1.2, 4.0, 6.8 buffer solution and water). Twenty six healthy male subjects, $23.35{\pm}1.57$ years in age and $66.29{\pm}10.61kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 20 mg as epinastine hydrochloride was orally administered, blood was taken at predetermined time intervals and the concentrations of epinastine in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t.\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Alesion tablet, were 1.50, 1.46 and -13.48% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25(e.g., log 0.95$\sim$log 1.12 and log 0.93$\sim$log 1.10 for $AUC_t\;and\;C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating S-napine tablet 10 mg was bioequivalent to Alesion tablet.

• Journal of Pharmaceutical Investigation
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• v.38 no.3
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• pp.199-205
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• 2008

Famciclovir, 9-(4-hydroxy-3-hydroxymethylbut-1-yl) guanine, is an oral prodrug of the antiherpesvirus nucleoside analogue, penciclovir. In human, famciclovir is orally well absorbed and then undergoes extensive first pass metabolism to penciclovir and essentially no parent compound is recovered from plasma or urine. The purpose of the present study was to evaluate the bioequivalence of two famciclovir tablets, Famvir tablet 750 mg (Novartis Korea Ltd.) and Famcivir tablet 750 mg (Hanmi Pharmaceutical. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of famciclovir from the two famciclovir formulations in vitro was tested using KP VIII Apparatus II method with water. Twenty six healthy male subjects, $23.38{\pm}1.72$ years in age and $68.59{\pm}7.84\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 750 mg as famciclovir was orally administered, blood samples were taken at predetermined time intervals and the concentrations of penciclovir in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations ere similar at water. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Famvir^{(R)}$ tablet 750 mg, were -0.53%, 1.12% and -24.82% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., $log\;0.9569{\sim}log\;1.0423$ and $log\;0.8763{\sim}log\;1.2136$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Famcivir tablet 750 mg was bioequivalent to Famvir tablet 750 mg.

• Journal of Yeungnam Medical Science
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• v.16 no.1
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• pp.25-33
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• 1999

Benzodiazepines(BZDs) are among the most widely prescribed drugs in the world. They are potent anxiolytic, antiepileptic, hypnotic, and muscle relaxing agents. There is an emerging model of the role of several neural systems in anxiety and their relation to the mechanism of action of BZDs. It has been postulated that BZD drugs exert their anxiolytic action by regulating GABAergic transmission in limbic areas such as the amygdala, in the posterior hypothalamus, and in the raphe nuclei. The involvement of the amygdala in the behaviors triggered by fear and stress has been suggested by many previous studies. In this review, reports about regulatory effects of endogenous BZD receptor ligands on the perception of anxiety and memory consolidation were summerized. These findings further support the contention that BZD receptor ligands modulate memory consolidation of averse learning tasks by influencing the level of stress and/or anxiety that accompanies a learning experience. The findings suggest that the decrease in the limbic levels of BZD-like molecules seen after the various behavioral procedures represent a general response to stress and/or anxiety, since it occurs in proportion to the level of stress and/or anxiety that accompany these tasks. In addition, these findings further support the hypothesis that the $GABA_A$/BZD receptor complex in limbic structures plays a pivotal role in the stress and anxiety.

• Journal of Pharmaceutical Investigation
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• v.37 no.4
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• pp.223-227
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• 2007

A rapid, simple and sensitive LC/MS/MS method for the determination of lercanidipine in human serum was validated and applied to the pharmacokinetic study of lercanidipine. Lercanidipine and internal standard, amlodipine, were extracted from human serum by liquid-liquid extraction with hexan-isoamyl alcohol (100: 1, v/v) and analyzed on a $Symmetry^{(R)}$ MS $C_{18}$ column with the mobile phase of acetonitrile-0.2% aqueous formic acid (70: 30, v/v). Using MS/MS with multiple reaction monitoring (MRM) mode, lercanidipine and amlodipine were detected without severe interferences from human serum matrix. Lercanidipine produced a protonated precursor ion ($[M+H]^+$) at m/z 612.3 and a corresponding product ion at m/z 280.0. Internal standard produced a protonated precursor ion ($[M+H]^+$]) at m/z 409.0 and a corresponding product ion at m/z 238.0. The ruggedness of this method was investigated using quality control (QC) samples. This method showed linear response over the concentration range of 0.05-20 ng/mL with correlation coefficient greater than 0.999. The lower limit of quantitation using 0.5 mL of serum was 0.05 ng/mL, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the developed method ranged from 85.51 to 112.2% for lercanidipine with overall precision (% C.V.) being 3.56-13.1%. This method showed good ruggedness (within 15% C.V.) and was successfully applied for the analysis of lercanidipine in human serum samples for the pharmacokinetic studies, demonstrating the suitability of the method.

• YAKHAK HOEJI
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• v.52 no.4
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• pp.299-305
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• 2008

Gabapentin, 1-(aminomethyl) cyclohexaneacetic acid, is a amino acid derivative, and is clinically effective in the treatment of neuropathic pain and partial seizures of epilepsy as a complementary therapy. The purpose of the present study was to evaluate the bioequivalence of two gabapentin tablets, $Neurontin^{R}$ tablet 800 mg (Pfizer Pharmaceuticals Co., Ltd.) and Gabapenin tablet 800 mg (Hanmi Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of gabapentin from the two gabapentin formulations in vitro was tested using KP VIII Apparatus II method with 0.06 M HCI dissolution media. Twenty six healthy male subjects, $23.85{\pm}2.24$ years in age and $69.40{\pm}11.11$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ crossover study was employed. After a single tablet containing 800 mg as gabapentin was orally administered, blood samples were taken at predetermined time intervals and the concentrations of gabapentin in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution media. The pharmacokinetic parameters such as $AUC_{t}$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_{t}$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Neurontin^{R}$, were 1.28%, 0.63% and 0.62% for $AUC_{t}$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., $log0.9097{\sim}log1.1598$ and $log0.8919{\sim}log1.1262$ for $AUC_{t}$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Gabapenin tablet 800 mg was bioequivalent to $Neurontin^{R}$ tablet 800 mg.

• The Journal of the Korean dental association
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• v.49 no.11
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• pp.688-703
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• 2011

Park Myoung Jin (1903-1957) was a respectable leader who disseminated dental medical education to make our path as the leading dental medical education developing a new global history of dental medicine. Dr. Park was born in Seoul on 3 July 1903. He graduated Kyongseong dental medical school and studied at the pharmacology department achieving his M.D. In 1938, as the president representing the Hanseong dentists association equivalent to the Japanese dentists association, Dr. Park participated in various events. After liberation, Dr. Park tried his best to achieve Korean dental medical education as the pursuit of ideal ego with self-centered ego. He reorganized the Kyongseong dental medical school and incorporated it to the Seoul National University dental college. Even during the Korea war, Dr. Park still sincerely carried out his duties as the director of the Seoul National University dental medical college by recruiting university entrants and turned out graduates. In 1954, Dr. Park as the director of the Seoul National University dental medical college, he frontiered an opportunity to adapt the American dental medicine by sending school staffs to study overseas. On 25 June 1954, Dr. Park received 25 years of meritorius service award presented by Seoul National University Dental Medical College. Further, on 6 Aril 1954, Dr. Park became a member of an academic research committee. In April 1946, Dr. Park was elected as the president of the Chosun Dentists Association(Korean Dental Association). On 19 May 1947, Dr. Park was also appointed as the director of the Korea dental medicine association leading the general meetings and academic conferences from 2nd through the 8th sessions. On 30 November 1954, as the president of the Korea dental medicine association, Dr. Park also published the Korea dental association publications. In 1957, Dr. Park donated the school housing for the principle of the Kyongseong dental medical school establishing the basis for the Korea dentists association center. Dr. Park also participated in establishment of the oral hygiene campaigne, dental administration policy, organization of the specialized subject delegation board members and the dental materials association. On 10 December 1955, we can recognize Dr. Park's respective historical consciousness through his declaration 'history is a true record of historical traces of a national'. Dr. Park was a living witness of the Korean dental industry. Especially, he stated that the origin of the Korean dentists association was in the Hanseong dentists association. Dr. Park overcame the pressure and indignity during the Japanese colonization. The joy of liberation did not last long since he also had to experience the fraticidal tragedy of the Korea war. Dr. Park was a professional dental specialist and a leader researching dental medicine. He was a great leader who understood the dental medicine and dedicated for the dentist association and dental medicine association with compassion for the nation and national as a Korean.

• The Korean Journal of Rehabilitation Nursing
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• v.4 no.2
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• pp.179-186
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• 2001

The purpose of this study is to develop a systematic and efficient curriculum for the rehabilitation nurse specialist program. This research was carried out as a group work of 15 experts in order to share various opinions about the curriculum, and also through literature review. Articles, curriculums of other Clinical Nurse Specialist Programs, medical laws guidelines, as well as Clinical Nurse Specialist Program from the Korean Nurses Association were reviewed, and the issue was discussed throughly via group meetings. The developed curriculum is as follows: 1. Educational philosophy lies in the fact that the rehabilitation nurses support the patients to maximize their potential and functional level, so that they could maintain healthy state and re-adapt to changed environment. Furthermore the rehabilitation nurses are disposed of arbitrary decision power under their own responsibility, thus they take charge of welfare and healthy environment of the local society through the patients(subjects) and local resources. 2. Educational goals are to train rehabilitation nurse specialist, who correspond to the social needs, so to say, those who have the knowledge and skills for nursing practice, education and research. 3. The curriculum consists of 37 credits, of which 24 credits are based on lectures and 13 credits based on clinical practice. General courses are 3 subjects (5 credits) ; nursing theory, nursing research, and laws/ethics. Mandatry courses are 8 subjects with 19 credits; advanced physical assessment, pharmacology, pathophysiology, issues in rehabilitation nursing, advanced rehabilitation nursing intervention I, advanced rehabilitation nursing intervention II, sports physiology, special rehabilitation nursing intervention. As for the clinical practice courses, assessment and evaluation for rehabilitation(64 hours), community and home based rehabilitation nursing(128 hours), hospital based rehabilitation nursing(128 hours), institution based rehabilitation nursing(96 hours) would be treated. 4. Contents of the curses were developed to correspond with the courses' objectives and specific items. 5. Evaluation would be carried out both in the lecture and in the clinical practice. The knowledge and skills of the students would be measured to ensure full validity and credibility. However this developed curriculum should be continuously modified and updated in more desirable direction.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.32-38
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• 2010

Activation of JNK has long been associated with the apoptotic response induced by various anti-cancer drugs including doxorubicin, vinblastine, and etoposide. In this study, we examined and compared patterns of apoptosis and JNK activation according to three different anti-cancer drugs (daunorubicin, vinblastine, and etoposide) and two different sources of HL60 cells (Jackson Laboratory and ATCC). HL60 cells from Jackson Laboratory (HL60/RPMI) were maintained in RPMI 1640 containing 5% fetal bovine serum and those from ATCC (HL60/IMDM) in IMDM containing 20% fetal bovine serum as to each manufacture's guideline. In general, HL60/RPMI cells were more sensitive to anti-cancer drugs compared to HL60/IMDM cells, demonstrated by the XTT and flow cytometric analyses. Apoptotic pathways after treatment with anti-cancer drugs seemed to be different between HL60/RPMI (daunorubicin and etoposide, caspase 3 dependent, but caspase 8 or 9 independent; vinblastine, caspase 3 independent) and HL60/IMDM (caspase 3 and caspase 9 dependent). The expression of apoptotic protein, BID, was consistent with caspase 3 activation. Immunoblotting of phospho-JNK and JNK kinase assay showed JNK activation by all three anti-cancer drugs in HL60/RPMI, while JNK activation was observed only in vinblastine-treated cells in HL60/IMDM. Our study results suggest that in vitro environmental conditions have a significant influence on JNK mediated apoptosis of HL60 cells by anti-cancer drugs and in vitro culture conditions are important factors in JNK or possibly other MAPK related studies.