• Title/Summary/Keyword: Dose-response

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Bioequivalence of Cholicerin Soft Capsule to Gliatilin Soft Capsule (Choline Alphoscerate 400 mg)

  • Kang, Hyun-Ah;Kim, Se-Mi;Kang, Seung-Rae;Kang, Min-Sun;Lee, Sang-No;Kwon, In-Ho;Yoo, Hee-Doo;Kim, Yoon-Gyoon;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.40 no.2
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    • pp.109-115
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    • 2010
  • The purpose of the present study was to evaluate the bioequivalence of two choline alphoscerate soft capsules, Gliatilin soft capsule (Daewoong Pharmaceuticals Co., Ltd.) and Cholicerin soft capsule (Sam Chun Dang Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Serum concentrations of choline after oral administration of choline alphoscerate were determined using a validated LC/MS/MS method. This method showed linear response over the concentration range of 0.5-20 ${\mu}g$/mL with correlation coefficient of 0.9999. The lower limit of quantitation using 100 ${\mu}L$ of serum was 0.5 ${\mu}g$/mL which was sensitive enough for pharmacokinetic studies. Thirty six healthy male Korean volunteers received each medicine at the choline alphoscerate dose of 1200 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Blood samples were taken at predetermined time intervals up to 8 hr. $AUC_t$ (the area under the serum concentration-time curve from time 0 to 8 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (the maximum serum drug concentration) and $T_{max}$ (the time to reach $C_{max}$) were compiled from the serum concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters, indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Cholicerin/Gliatilin were log0.9998-log1.1172 and log0.9938-1.0944, respectively. These values were within the acceptable bioequivalence intervals of log0.80-log1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Cholicerin soft capsule and Gliatilin soft capsule are bioequivalent.

Effect of Anti-atopic Allergic Reaction in Response to Oriental Herb Extracts (생약재 추출물의 아토피 완화효과)

  • Yang, Hee-Jin;Park, Kye-Won;Kim, Hyun-Suck;Cho, Soo-Muk;Park, Ki-Moon
    • Korean Journal of Food Science and Technology
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    • v.42 no.1
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    • pp.109-114
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    • 2010
  • The in vivo and in vitro effects of oriental herb extracts of Cassia obtusifolia, Taraxacum platycarpum and Ulmusmacrocarpa on anti-atopic allergic reaction were evaluated in this study. A mixture of these extracts exhibited more potent anti-allergic activities in human mast cells than those from individual extracts. The herbal mixture significantly inhibited the release of compound 48/80-induced $\beta$-hexosaminidase release in the human mast cell line, HMC-1. The mixture also suppressed the production of PMA and A23187-induced inflammatory cytokines in HMC-1 cells. To further investigate the in vivo effects of the herbal mixture, a Dermatophagoides farinae (DF)-induced atopic dermatitis mouse model was utilized. Oral administration of the herbal mixture significantly decreased the ear thickness and swelling in DF treated NC/Nga mice in a dose dependent manner. Furthermore, serum levels of IgE and interleukin-4 (IL-4) were significantly decreased, whereas interferon-gamma (IFN-$\gamma$) levels were increased in the mixture administrated groups when compared to the control. Taken together, our data indicate the possibility of using a mixture of the oriental herb extract to relieve symptoms of atopic dermatitis.

Primary Squamous Cell Carcinoma of the Parotid Gland (원발성 이하선 편평상피세포암종)

  • Lee Sang-Wook;Kim Gwi-Eon;Park Cheong-Soo;Park Won;Lee Chang-Geol;Keum Ki-Chang;Lim Ji-Hoon;Yang Wook-Ick;Suh Chang-Ok
    • Korean Journal of Head & Neck Oncology
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    • v.13 no.2
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    • pp.228-234
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    • 1997
  • Squamous cell carcinoma originating in the parotid gland has rare occurrence. The primary squamous cell carcinoma of the parotid gland comprise about 0.3% and 9.8% of all parotid malignant tumor. We investigated the clinical behavior and treatment outcome of patients with primary squamous cell carcinoma of the parotid gland. We reviewed all cases of possible primary squamous cell carcinoma of the parotid gland treated at Yonsei Cancer Center, Seoul, Korea, from 1981 through 1995. A total of 128 had primary parotid malignancy. Metastatic squamous cell carcinoma and mucoepidermoid carcinoma were excluded in this study. Ten cases of primary squamous cell carcinoma of the parotid gland were identified. 6 cases of them are men & 4 cases are women. The age of patients ranged from 31 to 68 years with median age of 55 years. On physical examination, 5 cases had palpated cervical neck node and 6 cases had facial nerve palsy. Staging was done according to the current guidelines established by the American Joint Committee on Cancer (1992). Two cases were stage I, 1 in stage III, and 7 in stage IV. Six cases were performed operation and postoperative radiation therapy. Four cases were treated by curative radiation therapy, dose of more than 65 Gy on parotid gland region. The 5 year actual survival rate and the 5 year disease free survival rate were 30.8%, and 40.0%. Initial complete response rate was 70% for all patients. Local failure were occurred 3 of 7 patients with local controlled cases, failure sites were primary site, ipsilateral cervical neck node, contralateral supraclavicular node. Most recurrences developed within 1 year of initial treatment. Distant metastasis was appeared 2 of 3 patients who did not achieved local control. Primary squamous cell carcinoma of the parotid gland occured infrequently. A retrospective study at the Yonsei Cancer Center indicates incidence of 7.8%. At diagnosis, advanced stage, neck node presentation, facial nerve paralysis were associated with a poor prognosis. These results may suggested that radical surgical excision may be treatment of choice and that planned postoperative radiotherapy may be bendicial for reducing locoregional recurrence rates.

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Bioconjugation by dual heterobifunctional coupling method: Use of the conjugates for the detection of dopamine (서로 다른 두 작용기를 이용한 결합법에 의한 접합체: 도파민 면역분석법)

  • Ryu, Ji-Eun;Rhee Paeng, In-Sook
    • Analytical Science and Technology
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    • v.23 no.6
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    • pp.537-543
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    • 2010
  • Dopamine (DA) is an important neurotransmitter molecule of catecholamines. Its deficiency could lead to brain disorder such as Parkinson's disease and schizophrenia. Therefore, it is necessary to establish a suitable analytical technique with sensitivity and simplicity. A competitive enzyme-linked immunosorbent assay for DA has been optimized and characterized. Assay sensitivity is controlled by two factors in competitive immunoassay. One is a nature and concentration of competitor, and the other is those of binder, antibody. Thus, optimization was performed: BSA-DA conjugate and antibody-avidin conjugate were prepared by dual heterobifunctional coupling method using SATA and SMCC. Assay condition was optimized with $6.66\;{\mu}gmL^{-1}$ of BSA-DA and $4.17{\times}10^{-10}\;M$ of antibody-avidin conjugate. A dose-response curve was constructed, and a limit of detection and a dynamic range for DA were accomplished to $2.3{\times}10^{-2}\;{\mu}g\;mL^{-1}$ and four orders of magnitude ($1.0{\times}10^{-7}\;M$ to $1.0{\times}10^{-3}\;M$), respectively. Calibration curve was constructed on dynamic range and least-squares regression of this data gave the following relationship: absorbance = -0.1098 log[DA]+0.0353 ($R^2$ = 0.9956).

Effect of Photoperiod on Radiation-Induced Pink Mutations in Tradescantia Stamen Hairs (자주달개비 수술털에서 방사선에 의해 유발되는 분홍돌연변이에 대한 광주기의 영향)

  • 김원록;김진규
    • Korean Journal of Environmental Biology
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    • v.17 no.3
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    • pp.331-335
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    • 1999
  • The present study was carried out to investigate the combined effect of radiation and photoperiod (PP) regimes on Tradescantia 4430 somatic cell mutations. Potted plants were irradiated with 0.3, 0.5 and 1.0 Gy of gamma radiation from 60Co source. The plants irradiated only with gamma radiation were used as control group (CT). The somatic cell mutation rate in 0.5 Gy irradiated CT and PP20 group started to increase on the 6th day and reached a maximum value on the l0th day and 9th day after irradiation while the rate in the experimental group under 4 hours of photoperiod a day (PP4) started to increase on the l0th day and reached a maximal value on the 16th day post-irradiation. The slope of dose-response curve in CT was 5.99 ($r^2$=0.99), while it was 6.93 ($r^2$=0.98) in PP20 and 11.74 ($r^2$=0.99) in PP4, respectively. The biological efficacy of radiation in the induction of pink mutation increased by 15.7% in PP20 and 95.9 % in PP4, respectively. It is suggested that photoperiod regimes unfavorable to the plant have an additive effect on radiation-induced mutations and a delaying or inhibiting effect on cell damage repair, as well.

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Conformal Radiotherapy in a Patient with Cancer at the base of the Tongue in a Previously Irradiated Area (방사선치료 조사영역 내에 발생한 설암 환자에서 입체조형방사선치료 경험 : 증례보고)

  • Cho Moon-June;Kim Ki-Hwan;Kim Byung-Kook;Song Chang-Joon;Kim Jun-Sang;Kim Jae-Sung;Jang Ji-Young
    • Korean Journal of Head & Neck Oncology
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    • v.17 no.1
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    • pp.59-62
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    • 2001
  • Objectives: We report an interim result of conformal radiotherapy in a patient with early stage cancer at the base of the tongue, which developed in a previously irradiated area. Materials and Methods: A 64-year-old male patient was diagnosed with T4N0M0 supraglottic cancer. He received 72Gy of radiation therapy from 21 November 1988 to 24 February 1989. He had local failure and underwent a salvage total laryngectomy on 28 August 1989. Subsequently, he did well. In early 1999, he suffered from throat pain. He had a 2.5cm ulcerative mass at the base of his tongue, in the area that had been irradiated previously. Biopsy showed squamous cell carcinoma. After workup, he was diagnosed with base of tongue cancer with T2N0M0. Surgery was not feasible because the morbidity was not acceptable. Since it was difficult to re-irradiate the area with a curable dose using conventional 2D radiation therapy with an acceptable morbidity, we decided to try conformal radiotherapy. We used 7 static beam ports with field sizes from $7x6.4\;to\;8x8cm^2$, using 6 and 10MV photons. The fractionation regimen was 1.8Gy, 5 times per week. He received 64.8Gy in 36 fractions from 9 April 1999 to 1 June 1999. Results: In the 21 months since radiotherapy, the patient has not experienced any acute or chronic complications, such as xerostomia. He experienced relief of pain shortly after the start of radiotherapy, showed a complete response, and is still doing well. Conclusion: Conformal radiotherapy can be used to treat cancer that develops within a previously irradiated field, with curative intent.

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Rhabdomyosarcoma Involving Maxillary Sinus and Orbit (상악동과 안와를 침범한 횡문근육종 1례)

  • Oh Yong-Suk;Kang Jin-Hyoung;Han Ji-Youn;Hong Young-Sun;Kim Hoon-Kyo;Lee Kyung-Shik;Kim Dong-Jip;Kim Min-Sik;Cho Seung-Ho;Suh Byung-Do;Yoon Sei-Chul
    • Korean Journal of Head & Neck Oncology
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    • v.10 no.2
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    • pp.218-224
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    • 1994
  • Soft tissue sarcoma of the head and neck is not frequent neoplasm, accounting for less than 1% of all malignant neoplasm in the region. The histological varieties include osteogenic sarcoma, malignant fibrous histiocytoma, rhabdomyosarcoma, fibrosarcoma, tenosynovial sarcoma, angiosarcoma and chondrosarcoma. Rhabdomyosarcomas of the head and neck usually occur in children under the age of 10 years (over 70%) and rarely develop in adults over the age of 20 years. The prevalent sites of involvement include the orbit, nasal cavity, external ear, paranasal sinus and soft tissue of mouth and the primary location of tumor is considered to be one of the important prognostic factors. Before the 1960s, when surgical resection was the only method of treatment, the 5-year survival rate was less than 20%, but recently it has been greatly improved by the multimodality treatment, combining surgery with chemotherapy and radiation therapy. Here we treated a rhabdomyosarcoma woman with three cycles of high dose chemotherapy followed by radiation therapy. After the, completion of preoperative treatments, successful result of more than partial response was achieved. Three months later total maxillectomy and radical neck dissection was performed. There was no evidence of tumor infiltration in the resected tumor and regional lymphnodes but metastasized tumor cells in cervical lymphnodes were detected. Tumor cell infiltration was also found on the bone marrow biopsy to evaluate the pancytopenia which occurred during postoperative recovery. Two months later she died of secondary bone marrow failure. We think that this multimodality treatment combining pre-operative chemotherapy, radiotherapy and surgery might play an important role in curative resection and eyeball preservation in patients with rhabdomyosarcoma involving the eyeball.

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Safety and Immunogenicity of Salmonella enterica Serovar Typhimurium llaB in Mice

  • CHO SUN-A;LEE IN-SOO;PARK JONG-HWAN;SEOK SEUNG-HYEOK;LEE HUI-YOUNG;KIM DONG-JAE;BACK MIN-WON;LEE SEOK-HO;HUR SOOK-JIN;BAN SANG-JA;LEE YOO-KYOUNG;PARK JAE-HAK
    • Journal of Microbiology and Biotechnology
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    • v.15 no.3
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    • pp.609-615
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    • 2005
  • The safety and immunogenicity of an attenuated recombinant Salmonella vaccine strain, Salmonella enterica serovar Typhimurium llaB, was assessed. This vaccine strain could survive in low pH condition, and its ability of intracellular survival did not differ from that of S. enterica serovar Typhimurium UK1, which is the wild-type of the vaccine strain. The mortality of the mice orally administered with the vaccine strain was $50\%$ at the dose of $10^7$ CFU. All mice administered with $10^5\;or\;10^3$ CFU of the vaccine strain survived for 3 days postinoculation (pi). However, all mice administered with more than $10^3$ CFU of the vaccine strain died within 3 days pi. To examine the protective effect of the vaccine strain, mice were orally immunized with $10^4\;and\;10^6$ CFU of the bacteria. Control mice were given with 0.5 ml of phosphate buffered saline (PBS). After 8 days, the mice were challenged with $10^9$ CFU of S. enterica serovar Typhimurium UK1, and mortality was examined for 5 days. The survival rates of the mice immunized with $10^4\;and\;10^6$ CFU of the vaccine strain were $60\%\;and\;80\%$, respectively, whereas all control mice died within 2 days after challenging. To investigate the immunogenicity of S. enterica serovar Typhimurium llaB, mice were orally immunized with $10^5\;or\;10^6$ CFU ml of the vaccine strain. Five mice of each group were sacrificed at 5 and 12 days after immunization, and results showed that immunization of the vaccine strain led to increases of IgG1, IgG2, and IgM titers against S. enterica serovar Typhimurium UK1 in mouse sera, cytokine expressions such as IL-2, IL-4, IL-6, and IL-10 in spleen, and the lymphocyte proliferation response to mitogens (concanavalin A or LPS) stimulation.

Suppressive Effects of Lees from Sweet Potato Soju on LPS-induced Inflammatory Responses in RAW 264.7 Cells (고구마 소주 주박에 의한 RAW 264.7 세포주에서 lipopolysaccharide로 유도된 염증 반응의 억제 효과)

  • Lee, Seung-Hoon;Kwon, Min-Jeong;Kim, Soon Young;Sohn, Ho-Yong;Shin, Woo-Chang;Kim, Jong-Sik
    • Journal of Life Science
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    • v.26 no.1
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    • pp.117-122
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    • 2016
  • In the current study, the ethanol extracts and their subsequent organic solvent fractions from lees of sweet potato soju were prepared and the prepared samples were designated as from KSD-E8-1 to KSD-E8-5. Their effects on cell viability and nitric oxide (NO) production in mouse macrophage RAW 264.7 cells were investigated. The results showed that the ethyl acetate fraction (KSD-E8-3) of lees extracts from sweet potato soju significantly decreased nitric oxide (NO) production in LPS-activated RAW 264.7 cells, whereas they did not affect cell viabilities. The fraction KSD-E8-3 reduced the expression of pro-inflammatory genes such as COX-2, iNOS and TNF-alpha and also decreased protein expression of iNOS in a dose dependent manner, which were detected with RT-PCR and Western blot analysis, respectively. In addition, we detected the expression of mitogen-activated protein kinases (MAPKs) such as p38, JNK, and ERK1/2 and their phosphorylated forms. The results indicated that the treatment of the fraction KSD-E8-3 did inhibit phosphorylation of p38, JNK, and ERK1/2 MAPKs, indicating that the fraction KSD-E8-3 regulates LPS-induced inflammatory response via suppressing MAPK signaling pathway. Overall, these results may contribute to understand the molecular mechanism of anti-inflammatory effects by the ethyl acetate fraction of lees extracts from sweet potato soju.

Repression of Cathepsin D Expression in Adipocytes by MicroRNA-145 (지방세포에서 microRNA-145에 의한 Cathepsin D의 발현 제어)

  • Kim, Hyun-Ji;Bae, In-Seon;Seo, Kang-Seok;Kim, Sang Hoon
    • Journal of Life Science
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    • v.24 no.7
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    • pp.798-803
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    • 2014
  • Cathepsin D (CtsD), an aspartyl peptidase, is involved in apoptosis, resulting in the release of cytochrome C from mitochondria in cells. Here, we investigated microRNA regulation of CtsD expression in 3T3-L1 cells First, we observed the expression of CtsD in cells in response to doxorubicin (Dox). As expected, the level of CtsD mRNA was increased in 3T3-L1 cells exposed to Dox in a dose-dependent manner. Cellular viability of ectopically expressed CtsD cells was also decreased. Next, we used the miRanda program to search for particular microRNA targeting CtsD. MiR-145 was selected as a putative controller for CtsD because miR-145 had a high mirSVR score. In a reporter assay, the luciferase activity of cells containing the CtsD 3'-UTR region was decreased in cells transfected with miR-145 mimic compared to that of a control. The level of CtsD expression was down-regulated in preadipocytes ectopically expressing miR-145 and up-regulated by an miR-145 inhibitor. Cells also suppressed miR-145 expression when exposed to Dox. The miR-145 inhibitor reduced the cellular viability of 3T3-L1 cells. Taken together, these data suggest that miR-145 regulates CtsD-mediated cell death in adipocytes. These findings may have valuable implications concerning the molecular mechanism of CtsD-mediated cell death in obesity, suggesting that CtaD could be a useful therapeutic tool for the prevention and treatment of obesity by regulating fat cell numbers.