• 응용통계연구
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• 제31권1호
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• pp.123-137
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• 2018

비선형 혼합효과 모형은 다양한 분야에서 반복 측정 자료를 분석할 때 주로 사용된다. 비선형 혼합효과 모형은 개체 내 변동(intra-individual variation)에 대해 고려하는 제 1단계 개별수준모델(individual-level model)과 개체간 변동(inter-individual variation)에 대해 고려하는 제 2단계 개체군모델(population model)의 두 단계로 구성되어 있다. 비선형 혼합효과 모형의 첫 번째 단계인 개별수준모델은 비선형 회귀모형의 모수를 추정하는 것으로 일반적인 비선형 회귀모형과 같고, 주로 보통최소제곱추정 방법을 사용하여 모수를 추정한다. 그러나 최소제곱추정방법은 가정된 비선형 함수가 자료에 의해 명시적으로 드러나지 않는 경우 모수의 추정값과 그 표준오차가 극단적으로 커지는 문제가 발생할 수 있다. 본 논문에서는 최근에 비선형 회귀모형에서 제안된 능형회귀(ridge regression) 방법을 비선형 혼합효과 모형의 제 1단계 개별수준모델에 도입함으로써 이러한 문제를 해결할 수 있는 새로운 추정방법을 제안하였다. 제안된 추정량은 모의실험 연구를 통하여 기존의 표준적인 추정량과 그 성능을 비교하였다. 또한 미국의 National Toxicology Program으로부터 얻어진 정량적 대량고속 스크리닝(quantitative high throughput screening) 실제 자료를 사용하여 추정 방법들을 비교하였다.

• 대한수의학회지
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• 제43권3호
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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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• 제36권6호
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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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• 제38권3호
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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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• 제16권1호
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• pp.25-33
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• 1999

세계적으로 그 처방률이 높은 약물들 중 하나인 benzodiazepine계 약물은, 강력한 불안해소작용, 항경련작용, 최면작용 및 근이완작용을 가지고 있다. Benzodiazepine계 약물의 약리작용기전과 관련하여 불안장애의 병인에서 각종 신경전달계의 역할은 밝혀지고 있다. Benzodiazepine 약물은 편도체와 같은 변연계, 우측 시상하부 및 raphe nuclei에서 GALA성 신경전달을 조절함으로써 불안해소 작용을 나타내는 것으로 보고되었으며, 공포와 스트레스로 인해 유발되는 행동에 있어서 편도체의 역할은 이미 여러 보고를 통해 시사된 바 있다. 본 종설에서는 GABA성 신경전달 조절작용이 있다고 보고된 내인성 benzodiazepine 수용체 배위자의 불안 및 스트레스 반응의 인지 조절작용 및 기억 형성과정 조절작용 등에 관한 연구결과들을 종합하여 본 결과 내인성 benzodiazepine 수용체 배위자들이 불쾌한 학습과정에 동반되는 스트레스와 불안의 정도에 영향을 미침으로써 기억 형성과정을 조절한다는 생각을 뒷받침해 주었다. 또한 각종 행동 검사후 나타나는 뇌조직의 benzodiazepine 유사 물질의 부위별(편도체, 해마, 중격) 농도 감소는 행동 검사에 수반되는 스트레스 및 불안 정도에 비례하므로, 이러한 물질의 감소는 스트레스 및 불안에 대한 변연계의 일반적인 반응으로 생각된다. 부가적으로 이러한 결과는 변연계의 $GABA_A$/benzodiazepine 수용체 복합체는 생체의 스트레스 및 불안반응의 생리, 생화학적 면에서 중추적인 역할을 한다는 생각을 할 수 있게 하는 결과라 할 수 있다.

• Journal of Pharmaceutical Investigation
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• 제37권4호
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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.

• 약학회지
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• 제52권4호
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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.

• 대한치과의사협회지
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• 제49권11호
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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.

• 재활간호학회지
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• 제4권2호
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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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• 제18권1호
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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.