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Effects on Response of Nervous Tissue to Samuljetong-tang after Damaged by Taxol Treatment or Sciatic Nerve Injury (사물제통탕(四物除痛湯)이 Taxol 처리 및 좌골신경 압좌 손상 후 신경조직 변화에 미치는 영향)

  • Youn, Sung-Sik;Kim, Chul-Jung;Cho, Chung-Sik
    • The Journal of Internal Korean Medicine
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    • v.33 no.2
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    • pp.126-144
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    • 2012
  • Background : Peripheral nerves more rapidly recover than central nerves. However, it has been known that the degree of reaction of axons of peripheral nerves is affected by distinctive characteristics of axons and environmental factors near the axons. Taxol is a widely used medicine as for ovarian, breast, lung and gastric cancer. However it causes patients difficulties under treatment due to its toxic and side effects, which include persistent pain. Objectives : This study reviewed how SJT extract in vitro and in vivo affects nerve tissues of a sciatic nerve damaged by Taxol. It also studied how SJT extract in vivo affects axons of the sciatic nerve after the sciatic nerve was damaged by pressing. Methods : After vehicle, Taxol, and Taxol plus SJT were treated respectively for tissue of the sciatic nerve in vitro and then tissues were observed using Neurofilament 200, Hoechst, ${\beta}$-tubulin, $S100{\beta}$, caspase-3 and anti-cdc2. SJT was also oral medicated by injecting Taxol into the sciatic nerve of in vivo rats. Tissues of the sciatic nerve and axons of DRG sensory nerves were then observed using Neurofilament 200, Hoechst, ${\beta}$-tubulin, $S100{\beta}$, caspase-3 and p-Erk1/2. After inflicting pressing damage to the sciatic nerve of in vivo rats, tissues of the sciatic nerve and DRG sensory nerve were observed using Neurofilament 200, Hoechst, $S100{\beta}$, caspase-3, anti-cdc2, phospho-vimentin, ${\beta}1$-integrin, Dil reverse tracking and p-Erk1/2. Results : The group of in vitro Taxol plus SJT treatment had meaningful effects after sciatic nerve tissue was damaged by Taxol. The group of in vivo SJT treatment had effects of regenerating Schwann cells and axons which were damaged by Taxol treatment. The group of in vivo SJT had effects of regenerating axons in damaged areas after the sciatic nerve was damaged by pressing, and also had variations of distribution in Schwann cells at DRG sensory nerves and axons. Conclusions : This study confirmed that SJT treatment is effective for growth of axons in the sciatic nerve tissues and improvement of Schwann cells after axons of the sciatic nerve tissues was damaged. After tissues of sciatic nerve was damaged by pressing in vivo, SJT treatment had effects on promoting regeneration of axon in the damaged area and reactional capabilities in axons of DRG sensory nerves.

Selective Estrogen Receptor Modulation by Larrea nitida on MCF-7 Cell Proliferation and Immature Rat Uterus

  • Ahn, Hye-Na;Jeong, Si-Yeon;Bae, Gyu-Un;Chang, Minsun;Zhang, Dongwei;Liu, Xiyuan;Pei, Yihua;Chin, Young-Won;Lee, Joongku;Oh, Sei-Ryang;Song, Yun Seon
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.347-354
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    • 2014
  • Larrea nitida is a plant that belongs to the Zygophyllaceae family and is widely used in South America to treat inflammatory diseases, tumors and menstrual pain. However, its pharmacological activity remains unclear. In this study we evaluated the property of selective estrogen receptor modulator (SERM) of Larrea nitida extracts (LNE) as a phytoestrogen that can mimic, modulate or disrupt the actions of endogenous estrogens, depending on the tissue and relative amount of other SERMs. To investigate the property of SERM of LNE, we performed MCF-7 cell proliferation assays, estrogen response element (ERE)-luciferase reporter gene assay, human estrogen receptor (hER) binding assays and in vivo uterotrophic assay. To gain insight into the active principles, we performed a bioassay-guided analysis of LNE employing solvents of various polarities and using classical column chromatography, which yielded 16 fractions (LNs). LNE showed high binding affinities for $hER{\alpha}$ and $hER{\beta}$ with $IC_{50}$ values of $1.20{\times}10^{-7}$ g/ml and $1.00{\times}10^{-7}$ g/ml, respectively. LNE induced $17{\beta}$-estradiol (E2)-induced MCF-7 cell proliferation, however, it reduced the proliferation in the presence of E2. Furthermore, LNE had an atrophic effect in the uterus of immature rats through reducing the expression level of progesterone receptor (PR) proteins. LN08 and LN10 had more potent affinities for binding on $hER{\alpha}$ and ${\beta}$ than other fractions. Our results indicate that LNE had higher binding affinities for $hER{\beta}$ than $hER{\alpha}$, and showed SERM properties in MCF-7 breast cancer cells and the rat uterus. LNE may be useful for the treatment of estrogen-related conditions, such as female cancers and menopause.

Tamoxifen Induces Mitochondrial-dependent Apoptosis via Intracellular Ca2+ Modulation (탐옥시펜에 의해 유도된 세포 내 칼슘농도 변화와 미토콘드리아 의존적 세포사멸)

  • Jang, Eun-Seong;Kim, Ji-Young;Kim, Byeong-Gee
    • Journal of Life Science
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    • v.17 no.8 s.88
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    • pp.1053-1062
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    • 2007
  • In the present work, we show that tamoxifen(Tam)-induced cytotoxicity is due to the mitochondrial-dependent pathway triggered by the intracellular $Ca^{2+}$ increase in MCF-7 human breast cancer cells. Tam induced the intracellular $Ca^{2+}$ increase. According to the experimental results with $Ca^{2+}$ channel blockers, Tam-induced $Ca^{2+}$ uptake seemed to depend on the voltage-sensitive $Ca^{2+}$ channel at the early stage, but at later stages the intracellular $Ca^{2+}$ increases are more likely due partly to the release of stored $Ca^{2+}$ and partly to the capacitative $Ca^{2+}$ or other entry pathways. Tam-induced $Ca^{2+}$ increase led to the release of cytochrome c from mitochondria into the cytosol and the change of mitochondrial membrane potential. In MCF-7 cells, caspase-7 plays a key role in the downstream of apoptosis because caspase-3 is absent. In the cells treated with Tam, caspase-7 cleavage was increased almost two-fold. There was no marked alteration in the level of anti-apoptotic Bcl-2 protein; however, the cells showed increased expression of pro-apoptotic Bax protein more than two-fold in response to Tam. These results imply that the apoptotic signaling pathway activated by Tam is likely to be mediated via the mitochondrial-dependent pathway.

The Effects of Health Fitness and Body Composition in Elderly Men for 16 Weeks of Tai Chi Exercise (16주간의 태극권 운동이 남자 고령자들의 건강체력 및 신체조성에 미치는 영향)

  • Kim, Cheol-Woo
    • Journal of Life Science
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    • v.21 no.8
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    • pp.1127-1133
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    • 2011
  • Exercise has been shown to positively influence quality of life for elderly men with a wide variety of medical illnesses. Tai chi exercise, a slow and graceful form of exercise and meditation, has especially been offered as the ideal exercise for elderly men with diverse conditions, such as people suffering from chronic heart failure or breast cancer survivors. In one recent study, Tai Chi was found to improve exercise capacity, sleep stability, and quality of life in heart failure patients including elderly men. The purpose of the study was to examine the effects of 16 weeks of Tai Chi exercise (3 times/week, 60 min/trial, 40-50% HRR) on physical and physiological changes. Sixty four healthy volunteers without any particular disease between the ages of 65 and 79 years participated in the study. The results were as follows; Significant changes of cardiac endurance, strength, muscle endurance, flexibility and balance were observed following 16 weeks of Tai Chi exercise (p<0.05). In addition, significant changes of diastolic blood pressure, body fat and fat-free mass were observed following 16 weeks of Tai Chi exercise (p<0.05). These findings suggest that a brief period of Tai Chi exercise is beneficial, particularly to elderly men. It is especially beneficial for body composition, and physical fitness factors such as cardiopulmonary endurance, muscle endurance, flexibility, and balance. Further study is needed in this area for specific disease patients.

Video-assisted Thoracoscopy in the Treatment of Multi Loculated Pleural Effusion and Empyema (다방성 흉막수 및 노흉 환자에서 비디오 흉강경의 치료)

  • 김영진
    • Journal of Chest Surgery
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    • v.37 no.2
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    • pp.160-165
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    • 2004
  • Successful treatment of multi-loculated pleural effusion or thoracic empyema requires effective drainage and definitive diagnosis of causative organism. The purpose of this study was to assess the efficacy of the video-assisted thoracoscopic surgery in the management of thoracic empyema or multi-loculated pleural effusion after chest tube drainage treatment had failed. Material and Method: Between April 2000 and July 2002, 20 patients with thoracic empyema or multi-loculated pleural effusion that failed to chest tube drainage or other procedures who underwent an operation. All patients were assessed by chest-computed tomogram and underwent video assisted thoracoscopic drainage, debridement, biopsy and irrigation of pleural cavity. Result: In 18 cases (90%), underwent successful video-assisted thoracoscopic surgery. In 2 cases, decortications by mini-thoracotomy were necessary. The ratio of sex was 4 : 1 (16 male: 4 female), mean age was 48.9 years old (range, 17∼72 years), mean duration of postoperative chest tube placement was 8.2 days (range, 4∼22 days), mean postoperative hospital stay was 15.2 days (range, 7∼33 days). Causative disease was tuberculosis, pneumonia, trauma and metastatic breast cancer, There were no major postoperative complications. Symptoms improved in all patients and were discharged with OPD follow up. Conclusion: In an early organizing phase of empyema or multi loculated pleural effusion, video-assisted thoracoscopic drainage and debridement are safe and suitable treatment.

Determination of 4 Parabens in Human Urine by Online SPE and LC-MS/MS Techniques (온라인 고체상추출과 LC-MS/MS 기술을 이용한 소변 중 파라벤류 분석)

  • Kim, Jung Hoan;Kho, Young Lim;Kim, Pan Gyi;Jeong, Jee Yeon;Lee, Eun Hee;Lee, Seung-Youl;Nam, Hye-Seon;Rhee, Gyu-Seek
    • Journal of Environmental Health Sciences
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    • v.38 no.6
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    • pp.561-567
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    • 2012
  • Objectives: Parabens are widely used as antimicrobial agents in pharmaceuticals and cosmetics as well as by the food industry. Parabens have been reported to show weak estrogenic activity and be related to health effects such as allergic reactions and skin and breast cancer. We evaluated an online solid phase extraction (SPE) method coupled with LC-MS/MS technique using free and conjugated parent parabens in human urine for assessing human exposure to parabens. Methods: We employed LC/MS/MS through online solid phase extraction and column-switching techniques and analyzed free and conjugated parabens as biomarkers of human exposure. Four major parabens, methyl-paraben (MP), ethyl-paraben (EP), propyl-paraben (PP) and butyl-paraben (BP), were analyzed. Method validation was performed by sensitivity, accuracy, precision and comparison of the results of online SPE with offline SPE. Results: The limits of detection (LOD) were in the range of 0.2-2 ng/mL, and actual limits of quantification (LOQ) were in the range of 0.7-6 ng/mL urine, depending upon the compound. Accuracy was in the range of 98.3-106.4%, and precision was in the range of 1.3-8.7% (CV) depending upon the compound. We found a good correlation between the results of analysis by online SPE method and that by off-line SPE method. Conclusions: The online SPE method showed proper LOD and validated accuracy, precision and good correlation with the offline method for analyzing parabens in urine.

Solid-Phase Refolding of Poly-Lysine fusion Protein of hEGF and Angiogenin (Poly-lysine이 연결된 hEGF와 angiogenin의 융합단백질의 고체상 재접힘)

  • Park, Sang-Joong;Ryu, Kang;Suh, Chang-Woo;Chai, Young-Gyu;Kwon, Oh-Byung;Park, Seung-Kook;Lee, Eun-Kyu
    • KSBB Journal
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    • v.17 no.2
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    • pp.153-157
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    • 2002
  • A fusion protein, consisting of a human epidermal growth factor as the recognition domain and human angiogenin as the toxin domain, can be used as a targeted therapeutic against breast cancer cells among others. The fusion protein was expressed as an inclusion body in recombinant E. coli, yet when the conventional solution-phase refolding process was used the refolding yield was very low due to severe aggregation, probably because of the opposite surface charge resulting from the vastly different pl values of each domain. Accordingly the solid-phase refolding process, which exploits the ionic interactions between a solid matrix and the protein, was tried, however the ionic binding yield was also very low regardless of the resins and pH conditions used. Therefore, to provide a higher affinity toward the solid matrix, six Iysine residues were tagged to the N-terminus of the hEGF domain. When cation exchange resins, such as heparin- or CM-Sepharose, were used as the matrix, the adsorption capacity increased 2.5~3-fold and the subsequent refolding yield increased nearly 15-fold compared to the conventional process. A similat result was also obtained when an Ni-NTA metal affinity resin was used.

Synthesis of I-125 Labelled Compound of Taxol Analogue for Radioimmunoassay (Taxol의 방사면역측정을 위한 I-125 표지화합물 합성)

  • 오옥두;금준섭;이양호;박용석;편웅범;최창운
    • Biomedical Science Letters
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    • v.3 no.2
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    • pp.125-130
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    • 1997
  • Taxol, an anticancer drug that has diterpenoid conformation, has been used as an effective chemotherapeutical agent in the treatment of breast and ovarian cancers. Because of its toxicity like other anticancer drugs, monitoring the taxol level in serum is important procedure during cancer therapy. The various monitoring methods using HPLC, ELISA, and RIA have been adopted, and RIA technique is known to be superior than other methods in trems of sensitivity and convenience. In this study, in order to develope taxol RIA system using $^{125}$I labelled antigen, first of all we synthesized taxol derivatives. 2'-hemisuccinyltaxol was obtained with about 80% yield by esterification of taxol at C-2' hydroxyl group on C-13 carbon with succinic anhydride. [$^{125}$I]iodotyramine was prepared with 58% labelling yield by radioiodination of tyramine and purified by gel chromatography. 2'-[$^{125}$I]iodotyramine-hemisuninyltaxol, $^{125}$I labelled antigen for taxol RIA, was synthesized with 96% yield from conjugation of 2'-hemisuccinyltaxol and [$^{125}$I]iodotyramine. Anti-taxol serum was produced from the rabbit immunized with 2'-hemisuccinyltaxol-BSA synthesized by 2'-hemisuccinyltaxol and BSA. The antiserum titer was determined by RIA using 2'-[$^{125}$I]iodotyramine-hemisuccinyltaxol. The titer of 1:20 was obtained with about 40% of B/T. The results suggest that taxol RIA using $^{125}$I labelled antigen can be applied to monitor the taxol level in serum.

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Effect of Gamiondam-tang (GMODT), a Polyherbal Formula on the Pharmacokinetics Profiles of Tamoxifen in Male SD Rats

  • Ryu, Eun-A;Kang, Su-Jin;Song, Chang-Hyun;Lee, Bong-Hyo;Choi, Seong-Hun;Han, Chang-Hyun;Lee, Young-Joon;Ku, Sae-Kwang
    • The Journal of Korean Medicine
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    • v.38 no.2
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    • pp.61-72
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    • 2017
  • Objectives: The effects of Gamiondam-tang (GMODT) co-administration within 5min on the pharmacokinetics (PK) of tamoxifen were observed as a process of the comprehensive and integrative medicine, combination therapy of tamoxifen with GMODT to achieve synergic pharmacodynamics and reduce toxicity on the breast cancer. Methods: After 50mg/kg of tamoxifen treatment, GMODT 100mg/kg was administered within 5min. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMODT treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen (Tmax, Cmax, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered rats using noncompartmental pharmacokinetics data analyzer programs. Results: Co-administration with GMODT induced increased trends of plasma tamoxifen concentrations to 1hr after end of administration, and then showed decreased trends of plasma tamoxifen concentrations, and especially significant (p<0.05) increases of plasma tamoxifen concentrations were demonstrated at 0.5hr after end of co-administration with GMODT and also related significant (p<0.05) decreases of $AUC_{0-inf}$ and $MRT_{inf}$ as compared with tamoxifen single formula treated rats, at dosage levels of tamoxifen 10 mg/kg and GMODT 100 mg/kg within 5 min, in this experiment. Conclusion: Based on the results of the present study, it is considered that single co-administration GMODT within 5min significantly inhibited the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen, can be influenced on the toxicity or pharmacodynamic of tamoxifen.

Effect of Gender-specific Bovine Serum Supplemented Medium on Cell Culture (성별 특이 소 혈청이 세포 배양에 미치는 영향)

  • Lee, Dong-Mok;Choi, Moon-Seok;Woo, Gyung-Il;Shin, Yu-Mi;Lee, Ki-Ho;Cheon, Yong-Pil;Chun, Tae-Hoon;Choi, In-Ho
    • Journal of Animal Science and Technology
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    • v.51 no.5
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    • pp.413-420
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    • 2009
  • The research has been aimed to investigate the effect of different sera including fetal bovine serum (FBS), male bovine serum (MS), female bovine serum (FS), and castrated-male bovine serum (C-MS) on cell proliferation, follicular maturation and ovulation in vitro. Established cell lines and primary cells were cultured in the culture media supplemented with different sera and cells proliferation was observed by cell counting and MTT assay. The results indicated that cell proliferation was significantly different for different serum source. Proliferation of bovine and human myogenic satellite cells was highest in MS. In contrast, proliferation of breast cancer cells and immune cells were the highest in FS and FBS, respectively. There was no difference in the rate of follicular growth, whereas the rate of ovulation was higher in FBS and C-MS. Finally, the wound healing effect and cell proliferation of 3T3-L1 cells showed that wound healing was fastest in FS and cell proliferation was higher in MS. These results suggest the importance of an optimal serum selection in the experiments involving cell culture system, and gender-specific Hanwoo sera may be used as a substitute to FBS.