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The anti-nociceptive effect of BPC-157 on the incisional pain model in rats

  • Jung, Young-Hoon;Kim, Haekyu;Kim, Hyaejin;Kim, Eunsoo;Baik, Jiseok;Kang, Hyunjong
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.22 no.2
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    • pp.97-105
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    • 2022
  • Background: The pentadecapeptide BPC-157 has been shown to have anti-inflammatory and wound healing effects on multiple target tissues and organs. Peptides have potent anti-inflammatory effects on periodontal tissues in rats with periodontitis. Few studies have investigated the effect of BPC-157 on pain after dental procedures or oral surgeries. The purpose of the present study was to investigate the antinociceptive effects of BPC-157 on postoperative incisional pain in rats. Methods: Sprague-Dawley rats were randomly divided into five groups: control (saline with the same volume), BPC10 (10 ㎍/kg of BPC-157), BPC20 (20 ㎍/kg of BPC-157), BPC40 (40 ㎍/kg of BPC-157), and morphine (5 mg/kg of morphine). A 1-cm longitudinal incision was made through the skin, fascia, and muscle of the plantar aspect of the hind paw in isoflurane-anesthetised rats. Withdrawal responses were measured using von Frey filaments at 0, 2, 6 h and 4, 7 d after incision. The formalin test was also performed to differentiate its anti-nociceptive effect from an inflammatory reaction or central sensitization. Pain behavior was quantified periodically in phases 1 and 2 by counting the number of flinches in the ipsilateral paw after injection with 30 µL of 5% formalin. Results: The threshold of mechanical allodynia was significantly increased in the BPC10, BPC20, BPC40 and morphine groups compared with that in the control group at 2 h. These increasing thresholds then returned to the levels of the control group. The BPC-157 group showed a much higher threshold at 4 days after incision than the control group. The thresholds of the BPC groups, except the morphine group, were normalized 7 days after incision. The flinching numbers of the BPC10, BPC20, BPC40 and morphine groups were significantly decreased in phase 1, but there was no decrease in the BPC-157 groups except the morphine group in phase 2. Conclusions: BPC-157 was effective only for a short period after incision. It was also effective during phase 1 but not during phase 2, as determined by the formalin test. BPC-157 might have a short antinociceptive effect, even though it has anti-inflammatory and wound healing effects.

Liver Protective Effect of the Co-treatment of Rhei Radix et Rhizoma and Silymarin on TAA-induced Liver Injury (대황과 실리마린의 병용투여의 간섬유화 보호 효과)

  • Il-ha Jeong;Sang-woo Ji;Seong-soo Roh
    • The Journal of Internal Korean Medicine
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    • v.44 no.3
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    • pp.402-417
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    • 2023
  • Objective: Liver fibrosis is a highly conserved wound-healing response and the final common pathway of chronic inflammatory injury. This study aimed to evaluate the potential anti-fibrotic effect of the combination of Rhei Radix et Rhizoma water extract (RW) and silymarin in a thioacetamide (TAA)-induced liver fibrosis model. Methods: The liver fibrosis mouse model was established through the intraperitoneal injection of TAA (1 week 100 mg/kg, 2-3 weeks 200 mg/kg, 4-8 weeks 400 mg/kg) three times per week for eight weeks. Animal experiments were conducted in five groups; Normal, Control (TAA-induced liver fibrosis mice), Sily (silymarin 50 mg/kg), RSL (RW 50 mg/kg+silymarin 50 mg/kg), and RSH (RW 100 mg/kg+silymarin 50 mg/kg). Biochemical analyses were measured in serum, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), and ammonia levels. Liver inflammatory cytokines and fibrous biomarkers were measured by Western blot analysis, and liver histopathology was evaluated through tissue staining. Results: A significant decrease in the liver function markers AST and ALT and a reduction in ammonia and total bilirubin were observed in the group treated with RSL and RSH. Measurement of reactive oxygen species and MDA revealed a significant decrease in the RSL and RSH administration group compared to the TAA induction group. The expression of extracellular matrix-related proteins, such as transforming growth factor β1, α-smooth muscle actin, and collagen type I alpha 1, was likewise significantly decreased. All drug-administered groups had increased matrix metalloproteinase-9 but a decreasing tissue inhibitor of matrix metalloproteinase-1. RSL and RSH exerted a significant upregulation of NADPH oxidase 2, p22phox, and p47phox, which are oxidative stress-related factors. Furthermore, pro-inflammatory proteins such as cyclooxygenase 2 and interleukin-1β were markedly suppressed through the inhibition of nuclear factor kappa B activation. Conclusions: The administration of RW and silymarin suppressed the NADPH oxidase factor protein level and showed a tendency to reduce inflammation-related enzymes. These results suggest that the combined administration of RW and silymarin improves acute liver injury induced by TAA.

Estimation of genetic correlations and genomic prediction accuracy for reproductive and carcass traits in Hanwoo cows

  • Md Azizul Haque;Asif Iqbal;Mohammad Zahangir Alam;Yun-Mi Lee;Jae-Jung Ha;Jong-Joo Kim
    • Journal of Animal Science and Technology
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    • v.66 no.4
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    • pp.682-701
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    • 2024
  • This study estimated the heritabilities (h2) and genetic and phenotypic correlations between reproductive traits, including calving interval (CI), age at first calving (AFC), gestation length (GL), number of artificial inseminations per conception (NAIPC), and carcass traits, including carcass weight (CWT), eye muscle area (EMA), backfat thickness (BF), and marbling score (MS) in Korean Hanwoo cows. In addition, the accuracy of genomic predictions of breeding values was evaluated by applying the genomic best linear unbiased prediction (GBLUP) and the weighted GBLUP (WGBLUP) method. The phenotypic data for reproductive and carcass traits were collected from 1,544 Hanwoo cows, and all animals were genotyped using Illumina Bovine 50K single nucleotide polymorphism (SNP) chip. The genetic parameters were estimated using a multi-trait animal model using the MTG2 program. The estimated h2 for CI, AFC, GL, NAIPC, CWT, EMA, BF, and MS were 0.10, 0.13, 0.17, 0.11, 0.37, 0.35, 0.27, and 0.45, respectively, according to the GBLUP model. The GBLUP accuracy estimates ranged from 0.51 to 0.74, while the WGBLUP accuracy estimates for the traits under study ranged from 0.51 to 0.79. Strong and favorable genetic correlations were observed between GL and NAIPC (0.61), CWT and EMA (0.60), NAIPC and CWT (0.49), AFC and CWT (0.48), CI and GL (0.36), BF and MS (0.35), NAIPC and EMA (0.35), CI and BF (0.30), EMA and MS (0.28), CI and AFC (0.26), AFC and EMA (0.24), and AFC and BF (0.21). The present study identified low to moderate positive genetic correlations between reproductive and CWT traits, suggesting that a heavier body weight may lead to a longer CI, AFC, GL, and NAIPC. The moderately positive genetic correlation between CWT and AFC, and NAIPC, with a phenotypic correlation of nearly zero, suggesting that the genotype-environment interactions are more likely to be responsible for the phenotypic manifestation of these traits. As a result, the inclusion of these traits by breeders as selection criteria may present a good opportunity for developing a selection index to increase the response to the selection and identification of candidate animals, which can result in significantly increased profitability of production systems.

Experimental Fetal Cardiopulmonary Bypass in the Fetal Lamb Model (태아양 모델을 이용한 실험적 태아 심폐우회술)

  • 이정렬;임홍국;김원곤;김종성;최정연;김용진
    • Journal of Chest Surgery
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    • v.32 no.6
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    • pp.495-503
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    • 1999
  • Background: We tested the technical feasibility of fetal cardiac bypass and collected baseline data on the fetal hemodynamics and placental functions related to the cardiopulmonary bypass in the fetal lamb model. Material and Method: Eleven fetuses at 120 to 150 days of gestation were subjected to bypass via trans-sternal approach with a 12 G pulmonary arterial cannula and 14 to 18 F venous cannula for 30 minutes. All ewes received general anesthesia with ketamine. In all the fetuses, no anesthetic agents were used except muscle relaxant. Eight served as a group in which placenta was excluded from the extracorporeal circulation by clamping the umbilical cord during the bypass(the oxygenator group) and in the remaining three, the placenta worked as the only source of oxygen supply(the placenta group). Observations were made every 10 minute during a 30-minute bypass and 30-minute post bypass period. No prostaglandin inhibitors were used both in ewes and in fetuses. Result: Weights of the fetuses ranged from 1.9 to 5.2 kg. In the oxygenator group, means of arterial pressure, PaO2, atrial pressure, heart rate, and bypass flow rate ranged 69.8 to 82.6 mmHg, 201.7 to 220.9 mmHg, 4.1 to 4.3 mmHg, 169 to 182/min, and 140.3 to 164.0 ml/kg/min, respectively during bypass, but rapid deterioration of the fetal cardiac functions and the placental gas exchange was observed after the cessation of bypass. In the placenta group, means of arterial pressure decreased from 44.7 to 14.4 mmHg and means of PaCO2 increased from 61.9 to 129.6 mmHg during bypass. Flow rate was suboptimal(74.3 to 97.0 ml/kg/min) during bypass. All hearts fibrillated immediately after the discontinuation of bypass. Conclusion: In this study, the technical feasibility of fetal cardiopulmonary bypass was confirmed in the fetal lamb model. However, further studies with modifications of the bypass including an addition of prostaglandin inhibitor, an application of the total spinal anesthesia on the fetus, a creation of more concise bypass circuit, and a use of active pump are mandatory to improve the outcome.

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In Vivo Image and Biodistribution of $^{123}I$-15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP) in Liposarcoma Bearing Nude Mice (지방육종형성 동물모델에서 $^{123}I$-15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP)의 생체분포와 생체영상)

  • Lee, Tae-Sup;Suh, Yong-Sup;Choi, Chang-Woon;Woo, Kwang-Sun;Chung, Wee-Sup;Lim, Soo-Jung;Lim, Sang-Moo;Awh, Ok-Doo
    • The Korean Journal of Nuclear Medicine
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    • v.35 no.5
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    • pp.324-333
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    • 2001
  • Purpose: $^{123}I$-labeled fatty acids have been used in the evaluation of regional myocardial energy metabolism. This study aimed to evaluate the usefulness of $^{123}I$-BMIPP as a liposarcoma-imaging agent. Materials and Methods: We compared in vitro uptakes between liposarcoma(SW872) and glioma(9L) cell lines, and examined biodistribution and in vivo images of $^{123}I$-BMIPP in liposarcoma-bearing nude mice. Cold-BMIPP was labeled with $^{123}I\;using\;Cu^{2+}$ as catalyst. After purification by Sep-pak, radiochemical purity was determined by TLC. We compared cellular uptake between glioma and liposarcoma after incubation of 5, 10, 15, 30, 60, 120, and 180 mins with culture medium containing $^{123}I$-BMIPP. The difference in biodistribution was determined between non-feeding (water only) group for 18 hr and feeding group in normal mice (n=6/group) at 0.5, 2, and 24 hr. In liposarcoma-hearing nude mice model, liposarcoma, SW872, ceil lines were injected subcutaneously into the felt thigh of nude mice. The biodistribution of $^{123}I$-BMIPP was evaluated at 0.5, 2, and 24 hr (n:5 / group) and in vivo Image of $^{123}I$-BMIPP was obtained with gamma camera at 2 and 24 hr in liposarcoma-hearing nude mice. Results: Radiolabeling yield and radiochemical purity were 95% and above 99%, respectively. SW872 cell line showed more increased uptake than 9L with 1.5 times at 180 mins. The clearance of $^{123}I$-BMIPP in various tissues was more delayed in the non-feeding group than in the feeding group, especially at delayed time (24 hr) in normal mice, and the major excreting organ was the gastrointestinal tract. In liposarcoma-bearing nude mice, tumor/blood ratio of $^{123}I$-BMIPP was 0.94, 0.75, and 1.38 and tumor/muscle ratio was 0.66, 1.53, and 1.11 at 0.5, 2, and 24hr, respectively. $^{123}I$-BMIPP was selectively localized in liposarcoma at 24 hr image. Conclusions: These results suggest that $^{123}I$-BMIPP can be used as a liposarcoma-imaging agent.

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Objectives and Contents of Basic Medical Sciences in Nursing Education (간호학 교육에서 기초의과학 교과목별 목표와 내용에 대한 연구)

  • 최명애;신기수
    • Journal of Korean Academy of Nursing
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    • v.29 no.6
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    • pp.1455-1468
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    • 1999
  • The purpose of this study was to investigate the objectives and contents of basic medical sciences at department of nursing in college of nursing, and junior college of nursing, thus ultimately providing the basic data to standardize the curriculum of the basic medical sciences in nursing education. Seventy eight professors who were in charge of teaching basic medical sciences to at 22 colleges of nursing/ department of nursing, and 20 junior colleges of nursing responded to the questionnaires that consisted of the questions regarding objectives and contents, of basic medical sciences. Based on the description of objectives, the description related to nursing, nurse, nursing science was cathegorized as on objective applicable to nursing science, the description related to medicine or clinical medicine as medical model, the description without description related to medicine was cathegorized as knowledge acquisition. The number of schools corresponding to each category were summerized in descending order. The objectives of basic medical sciences were categorized by concepts and number of schools corresponding to the categorized concept. The findings of the study are as follows ; 1. The subjects of basic medical science identified were physiology, anatomy, biochemistry, pathology, microbiology, and pharmacology in most colleges of nursing and junior colleges. Two colleges of nursing/department of nursing (9.1%) and 19 junior colleges of nursing(95%) did not offer biochemistry, 1 college of nursing /department of nursing(5%) did not offer pathology & pharmacology. 2 junior colleges of nursing (10%) did not offer pharmacology, 1 junior college of nursing(5%) did not offer pathology. The other 1 junior college of nursing did not offer microbiology. 2. Objectives of physiology were to acquire knowledge and understanding on human function in both 6 (50%) colleges and 5 junior colleges. Objectives of anatomy were to acquire knowledge on human structure in both 4 (57%) colleges and 2 (50%) junior colleges; knowledge applicable to nursing sciences in both 3 (42.8%) colleges and 2 (50%) junior colleges. Objectives of biochemistry was to obtain knowledge and understanding on biochemistry, and understanding of basic concepts about biochemistry. Objectives of pathology were to obtain knowledge and understanding on pathology in both 4 (57.1%) colleges and 5(62.5%) junior colleges. Objectives of microbiology were to acquire knowledge and understanding on microbiology in both 5(83.8%) colleges and 6(85.7%) junior colleges. Objectives of pharmacology were to acquire knowledge on pharmacology in both 7(100%) colleges and 8(100%) junior colleges. 3. Contents of physiology in 19 (100%) schools were membrane transport, digestion, circulation, nervous system and respiration. In 16(84.2%) were kidney and muscle, that in 13(68.4%) were endocrine physiology. In 11(57.9%) were introduction and that in 9(47.4%) were structure and function of cells. Contents of anatomy in 11(100%) schools were skeletal system, muscle system, digestive system, circulatory system, concepts regarding human structure. In 10(90.9%) schools were endocrine system and nervous system, and in 5(45.5%) schools were blood, urinary system and cell. Contents of biochemistry in 6(100%) schools were history of biochemistry, body regulating factor, bioenergy, health and nutrition, nutrition of cell, energy production system. In 5(83.3%) schools were metabolism of protein and carbohydrate and enzyme, and in 3(50%) schools were metabolism of energy and fat. Contents of microbiology in 13(100%) schools were environment and influenc of bacteria, virus, G(-) rods, purulent cocci, G(+) rods. In 10 (76.9%) were immunity, diphtheria, enterobacteria, and in 9(69.2%) were spirochete, rickettsia and clamydia, and that in 6(46.2%) were sterilization and disinfection. Contents of pathology in 14(100%) schools were cell injury and adaptation, inflammation, respiratory diseases, circulatory diseases. In 10(71.4%) were neurological disorders, in 8(57.1%) were immunity and disease, and in 7 (50%) were tumor and progressive changes. Contents of pharmacology in 15(100%) were cardivascular drugs, introduction to pharmacology, hypnotics, analgesics, local anesthetics, an ticonvulsants. In 12(80%) were drugs activity on sympathetic and parasympathetic nervous system, and in 11(73%) were sulfa drugs, antibiotics, drug abuse and addiction.

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Estimation of Genetic Parameters for Growth and Carcass Traits in Hanwoo Bull Populations (비거세 한우 집단에 있어 성장형질과 도체형질에 대한 유전모수의 추정)

  • Park, C. J.;Park, Y. I.
    • Journal of Animal Science and Technology
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    • v.45 no.1
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    • pp.23-32
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    • 2003
  • Genetic parameters for growth and carcass traits were estimated on the basis of the data from 3,415 heads of Hanwoo bulls tested at Livestock Improvement Main Center. The data were divided into two groups : the first period group consisted of 1,592 heads of bulls tested in individual pens from 1986 to 1990 and the second period group consisted of 1,823 heads of bulls tested in group pens from 1991 to 1996. The testing period was from 6 to 18 months of age in the first period group and 10 to 22 months of age in the second period group. The average daily gains during 6 to 12 months and 12 to 18 months were 1.01kg and 0.77kg, respectively, in the first period group and 0.80kg and 0.95kg in the second period group, and the compensated growth appeared to have occurred in the second period group. The heritability of body weight at 12 months estimated was 0.37 during the first period and 0.47 during the second period. The heritability of body weight at 18 months was 0.29 during the first period and 0.33 during the second period. The heritability of average daily gain during 6${\sim}$12 months estimated was 0.26 for the first period and 0.33 for the second period. The heritability of average daily gain during 12${\sim}$18 months estimated was 0.11 for the first period and 0.22 for the second period. The heritabilities of body weights and average daily gains estimated tended to be higher in the second period than in the first period. The heritability of body measurements at 12 months during the first period estimated was 0.30 for withers height, 0.25 for rump height, 0.11 for thurls width and 0.13 for chest girth. The heritability of body measurments at 12 months during the second period was 0.53 for withers height, 0.44 for rump height, 0.36 for thurls width and 0.56 for chest girth. The heritabilites of withers height, rump height, thurls width and chest girth at 18 months of age were 0.40, 0.22, 0.12 and 0.21 during the first period and 0.45, 0.42, 0.42 and 0.35 during the second period, respectively. The heritability of carcass traits estimated during the first period was 0.11 for carcass weight, 0.24 for dressing percent, 0.25 for eye muscle area, 0.18 for backfat thickness and 0.21 for carcass length. The heritabilities of carcass weight, dressing percent, eye muscle area, backfat thickness, carcass length and marbling score during the second period estimated were 0.32, 0.52, 0.33, 0.51, 0.58 and 0.31, respectively. The genetic correlations between the first and second periods estimated were higher than 0.8 for chest girth at 12 months, rump height at 18 months, carcass weight and dressing percent, but were lower for other traits.

Genetic Parameter Estimation of Carcass Traits of Hanwoo Steers (한우 거세우의 도체형질에 대한 유전모수 추정)

  • Hwang, Jeong-Mi;Kim, Sidong;Choy, Yun-Ho;Yoon, Ho-Baek;Park, Cheol-Jin
    • Journal of Animal Science and Technology
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    • v.50 no.5
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    • pp.613-620
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    • 2008
  • The genetic parameters used in National Hanwoo Genetic Evaluation(NHGE) were needed to be monitored and updated periodically for accounting any possible changes in population parameters due to selection and environmental changes. Genetic parameters were estimated with single and two-trait models with MTDFREML package using 2,791 carcass records of steers collected from Hanwoo Progeny Test Program(HPTP). Single and two-trait models gave similar parameter estimates for all traits. The heritability estimates from single and two-trait models for carcass weight(CW), dressing percentage(DP), eye muscle area(EMA), back fat thickness(BFT) and marbling score(MS) were 0.30, 0.30, 0.37, 0.44 and 0.44, respectively. The heritability estimates for all the traits except BFT were slightly lower than those used in NHGE but seemed to be within the acceptable ranges. However, further monitoring is needed because the data might not have fully reflected the changes such as carcass grading standards in performance testing program. In order to shift statistical model of NHGE from single trait model to multiple-trait model, the genetic correlations between carcass traits were estimated with pairwise two-trait models. The genetic correlation coefficients between CW and DP, between CW and EMA, between CW and BFT and between CW and MS were 0.44, 0.63, 0.17 and 0.06, respectively. Those between DP and EMA, between DP and BFT and between DP and MS were 0.29, 0.40 and 0.20. Those between EMA and BFT and between EMA and MS were -0.24 and 0.15, respectively. The genetic correlation coefficient between BFT and MS was 0.03.

Development and Evaluation of a Stage Matched Exercise Intervention Program for Elders - Application of the Tran Theoretical Model - (노인 운동행위 변화단계별 중재프로그램의 개발 및 평가 - 범이론적 모형의 적용 -)

  • Kwon, Yeun-Jung
    • Research in Community and Public Health Nursing
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    • v.13 no.2
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    • pp.205-215
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    • 2002
  • Objectives: This study was designed to develop and evaluate a stage matched exercise intervention program to effectively increase exercise behaviors in urban elders. Methods: The study included three phases: preliminary descriptive data collection, program development, and program evaluation. The data for the preliminary descriptive phase were collected between May and June 2001. The study participants were 89 urban elders who responded a questionnaire that included general characteristics, exercise related experiences, stage, and process of change in exercise behaviors. Data were analyzed using descriptive statistics, $x^2$-test, and content analysis. Development of the program was based on the preliminary data. and a literature review, and was guided by the tran theoretical model. It consisted of strategies to facilitate the process of changes used in each stage. Evaluation of the program was achieved from October to December 2001, using a case study method, in which eight urban female elders participated. Interviews were conducted on a weekly basis in the form of either an individual interview, or group discussion. Each elder subject received education in accordance with the program strategies and education materials. In the case that a subject's stage of change moved into another one, the scores for the process of change were re-measured. The data were analyzed using the content analysis technique. Results: The results were as follows: 1. Elders who participated in the preliminary data collection phase were over 75 years of age, and the majority of them were women. They had a higher educational level, and fewer number of illnesses than the subjects in other studies. Their stage of change was divided into pre-contemplation and maintenance. The social liberation scores were the highest across all stages of change. There was no difference between men and women on scores for processes of change in each stage. 2. The stage matched exercise intervention program that was developed in this study consisted of one counseling type program and three distinguished educational booklet materials. 3. The results of the case studies are as follows: 1) The study participants were 8 women between 75 and 87 years of age. At the first interviews, all of them were in the pre-contemplation stage. All of them reached the action stage before the 7th week. The scores for processes of change that were the focus in each stage increased more than the scores for other processes of change. During the early stages of change, experimental processes increased more than behavioral processes. However. this pattern was reversed during later stages of change. 2) Characteristics of the subjects in each stage were identical as presented at the tran theoretical model. The intervention strategies were effective in the transition occurred in any stage. 3) Barriers for exercise included unwillingness to exercise, fatigue, shortness of breath, and pain. Ways to overcome these barriers were 'learning an alternative exercise method that can be done at home', 'self-promising/ exercise-promising', and 'use of cues to exercise'. 4) The factors that affected the application of the program were consideration of age and personal preference in selecting an exercise pattern, individualized intervention, and use of education materials appropriate to elders. Women over 80 years of age preferred muscle strengthening and stretching exercise, because they can be easily done at home. They also preferred individualized interventions, materials that were easy to read, and education contents appropriate for elders. Conclusion: In conclusion, the stage matched exercise intervention program that considered the characteristics of the elders was effective to facilitate exercise behaviors of the elders.

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Pharmacokinetic Study of Pyrazinamide Related to the Mechanism of the Renal Excretion (Pyrazinamide의 신배설기전에 관한 약동학적 연구)

  • Choi, Eung-Sang;Shin, Sang-Goo;Lee, Sun-Hee;Choi, Cheol-Hee;Kim, Yong-Sik;Lim, Jung-Kyoo;Park, Chan-Woong
    • The Korean Journal of Pharmacology
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    • v.23 no.1
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    • pp.1-7
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    • 1987
  • The renal handling and tissue distribution of pyrazinamide were studied after administration of single dose intravenous injection for 15 min or constant infusion in New Zealand White rabbits. Peak pyrazinamide serum concentration ranged from 57.3 to $105.0{\mu}g/ml$ ($mean{\pm}SD;83.0{\pm}17.8$). The mean half-life of the a phase was $0.143{\pm}0.047$ hr while the ${\beta}$ phase ranged from 1.66 to 3.25 hr($mean{\pm}SD;2.38{\pm}0.57$). The mean steady-state volume of distribution in non-compartmental model was $0.935{\pm}0.362\;L/kg$ Excretion ratio of pyrazinamide was dramatically reduced from 1.02 to 0.30 when unbound serum pyrazinamide concentration was increased from 6.04 to $60.9\;{\mu}g/ml$. The urine flow dependency of renal clearance of pyrazinamide was demonstrated in steady-state serum concentration. The tissue/serum concentration ratio of pyrazinamide was highest in kidney and lowest in skeletal muscle among the tissues examined. The results suggested that a large fraction of pyrazinamide filtered by glomerulus and secreted by renal tubule was reabsorbed and this tubular reabsorption of pyrazinamide might be greatly influenced by urine flow.

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