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Effects of the mixed formulation of sorafenib and blue honeysuckle on the pharmacokinetics profiles of sorafenib

  • Kang, Hyun-Gu;Kang, Su-Jin;Ku, Sae-Kwang;Choi, Seong-Hun;Lee, Young-Joon
    • Journal of Society of Preventive Korean Medicine
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    • v.23 no.1
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    • pp.83-94
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    • 2019
  • Objective : This study investigated the effects of concentrated and lyophilized blue honeysuckle powders (BH) on the pharmacokinetics (PK) of sorafenib were observed. Method : The blood was collected at 0.5 hr before single oral treatment of sorafenib (40 mg/kg) or sorafenib with BH (400, 200 and 100 mg/kg) mixed formulas administration, and 0.5, 1, 2, 3, 4, 6, 8 and 24 hrs after the end of single or mixed formula administration. Plasma concentrations of sorafenib were analyzed using LC-MS/MS methods. Tmax, Cmax, AUC, $t_{1/2}$ and $MRT_{inf}$ of sorafenib were analysis as compared with sorafenib single treatment. Results : Single oral administration of mixed formulas induced significant increases of plasma sorafenib concentrations from 0.5 hr after end of administration throughout all blood collected time points, as compared with sorafenib single formula treated rats, and significant decreases of sorafenib Tmax with increases of Cmax, $AUC_{0-t}$ and $AUC_{0-inf}$ were detected in sorafenib and BH 400 mg/kg mixed formulation treated rats as compared with sorafenib single formula treated rats, respectively. Inaddition, sorafenib and BH 200 or 100 mg/kg mixed formula treated rats also showed significant increases of sorafenib Cmax, $AUC_{0-t}$ and $AUC_{0-inf}$, respectively. Conclusions : According to these results, mixed formulation of BH with sorafenib increased the bioavailability of sorafenib through the increment of the absorptions.

Effects of Aucuba japonica Extract on Oral Wound Healing (구강점막의 창상치유에 대한 식나무(Aucuba japonica) 추출물의 효과)

  • Shim Kyung-Mi;Kim Se-Eun;Choi Jeong-Yun;Park Joo-Cheol;Jeong Soon-Jeong;Lee Jae-Yeong;Bae Chun-Sik;Park Don-Hee;Kim Do-Man;Jeong Moon-Jin;Kang Seong-Soo
    • Journal of Veterinary Clinics
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    • v.23 no.1
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    • pp.55-60
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    • 2006
  • Aucuba japonica has variable pharmacological effects such as hepatoprotective, choleretic, hemodynamic, antimicrobial, and anti-inflammatory activities. This study was performed to investigate the effects of Aucuba japonica extract on oral wound healing. Aucubin was extracted from Aucuba japonica, and injected on either side of buccal mucosa of male mice. Artificial full thickness wounds were made on the site with 1.5 mm biopsy punch under sterile technique. The specimens had taken on day 1, 3, and 5 with 4 mm biopsy punch. Light microscopic examination and quantitative histologic analysis were performed for reepithelization, inflammatory cell infiltration. Reepithelization of the aucubin (0.1%) group was earlier than the control group. And the number of inflammatory cells of the aucubin group was lesser than the control group. In view of the results so far achieved, the aucubin extracted from Aucuba japonica may be useful for oral wound healing and it can be applied as a topical agent on the oral wound. Further research should be performed on the mechanism of aucubin on oral wound healing and proper formulation for effective topical agents.

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.

Endometrial histology and predictable clinical factors for endometrial disease in women with polycystic ovary syndrome

  • Park, Joon-Cheol;Lim, Su-Yeon;Jang, Tae-Kyu;Bae, Jin-Gon;Kim, Jong-In;Rhee, Jeong-Ho
    • Clinical and Experimental Reproductive Medicine
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    • v.38 no.1
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    • pp.42-46
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    • 2011
  • Objective: This study was aimed to investigate endometrial histology and to find predictable clinical factors for endometrial disease (hyperplasia or cancer) in women with polycystic ovary syndrome (PCOS). Methods: We investigated the endometrial histology and analyzed the relationship between endometrial histology and clinical parameters, such as LH, FSH, estradiol, testosterone, fasting and 2 hours postprandial glucose and insulin, insulin resistance, body mass index, endometrial thickness, menstrual status from 117 women with PCOS. Statistical analysis was performed with chi square and t-test, p-value<0.05 was considered as statistically significant. And receiver operating characteristic curve was used to find predictable clinical factors for endometrial disease and to decide the cuff off values. Results: In 117 women with PCOS, endometrial histologic profiles are as follows: proliferative phase in 90 women (76.9%), endometrial hyperplasia in 25 women (21.4%), and endometrial cancer in 2 women (1.7%). Of 25 women with endometrial hyperplasia, simple hyperplasia without atypia, complex hyperplasia without atypia and complex hyperplasia with atypia were diagnosed in 15 (12.8%), 6 (5.1%), 4 (3.4%) women, respectively. Age and endometrial thickness were significantly related with endometrial disease, p=0.013 and p=0.001, respectively. At the cut off level of 25.5 years in age, sensitivity and specificity predicting for endometrial disease were 70.4% and 55.6%, respectively (p=0.023). At the cut off level of 8.5 mm in endometrial thickness, sensitivity and specificity were 77.8% and 56.7%, respectively (p=0.000). Conclusion: In women with PCOS, the incidence of endometrial hyperplasia and cancer were 21.4% and 1.7%. The age and endometrial thickness may be used as clinical determining factors for endometrial biopsy.

Comparative Ultrastructure of Secretory Granules of the Submandibular Gland in the Korean Spider Shrew, Sorex caecutiens, the Lesser White-toothed Shrew, Crocidura suaveolens and the Big White-toothed Shrew, Crocidura lasiura

  • Jeong, Soon-Jeong;Bae, Chun Sik;Lee, Hye-Yon;Choi, Baik-Dong;Yoon, Myung-Hee;Jeong, Moon-Jin
    • Applied Microscopy
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    • v.42 no.4
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    • pp.186-193
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    • 2012
  • The ultrastructure of the secretory granules of the submandibular gland was examined in the Korean spider shrew, Sorex caecutiens, lesser white-toothed shrew, Crocidura suaveolens and big white-toothed shrew, C. lasiura. The mucous and serous acinar granules of S. caecutiens with a border of the lucid corona differed from those of C. suaveolens and C. lasiurar with a dense lateral border. The mucous acinar granules of C. lasiura with several bands producing a variety of patterns in the matrix were similar to those of C. suaveolens. The serous acinar granules of C. lasiura had a homogenous pale center surrounded by minute dense specks or had an unusual substructure showing a geometric pattern according to the inclusions in the pale matrix of the granules. This is the first report of an unusual substructure showing a geometric pattern of the serous acinar granules of C. lasiura. The myelin-like body was observed in the granular duct cell of the three species of shrew. The myelin-like body of S. caecutiens with layers of unit membranes was different from that of C. suaveolens and C. lasiura with paired membranes. Therefore, the layers composing of the paired membranes of the myelin-like body might be one of the characteristics of Crocidura.

EXPRESSION AND FUNCTIONAL CHARACTERIZATION OF ODONTOBLAST-DERIVED GENE: OD314 (상아모세포 관련 유전자, OD314의 발현과 기능 연구)

  • Kim, Doo-Hyun;Kim, Heung-Joong;Jeong, Moon-Jin;Son, Ho-Hyun;Park, Joo-Cheol
    • Restorative Dentistry and Endodontics
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    • v.29 no.4
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    • pp.399-408
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    • 2004
  • Odontoblasts are responsible for the formation and maintenance of dentin. They are known to synthesize unique gene products including dentin sialophosphoprotein (DSPP). Another unique genes of the cells remain unclear. OD314 was isolated from the odontoblasts/pulp cells of rats and partially characterized as an odontoblast-enriched gene (Dey et al., 2001). This study aimed to elucidate the biological function of OD314, relating to odontoblast differentiation and dentinogenesis. After determining the open reading frame (ORP) of OD314 by transient transfection analysis using green fluorescent protein (GPP) expression vector, mRNA in-situ hybridization, immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and western analysis were performed. The results were as follows: 1. In in-situ hybridization, OD314 mRNAs were expressed in odontoblasts of developing coronal and root pulp. 2. OD314 was a novel protein encoding 154 amino acids, and the protein was mainly expressed in cytoplasm by transient transfection analysis. 3. Mineralized nodules were associated with multilayer cell nodules in the culture of human dental pulp cells and first detected from day 21 using alizarin-red S staining. 4. In RT-PCR analysis, OD314, osteocalcin (OC) and DSPP strongly expressed throughout 28 days of culture. Whereas, osteonectin (ON) mRNA expression stayed low up to day 14, and then gradually decreased from day 21. 5. Western blots showed an approximately 17 kDa band. OD314 protein was expressed from the start of culture and then increased greatly from day 21. In conclusion, OD314 is considered as an odontoblast-enriched gene and may play important roles in odontoblast differentiation and dentin mineralization.

Comparison of Extruded and Moist Pellets for Growth Performance, Water Quality and Histology of Olive Flounder Paralichthys olivaceus in Jeju Fish Farm (제주도 양식현장 내 배합사료와 생사료의 급여가 넙치의 성장, 사육수질 및 조직성상에 미치는 영향 비교)

  • Kim, Sung-Sam;Kim, Kang-Woong;Kim, Kyoung-Duck;Lee, Bong-Joo;Lee, Jin-Hyeok;Han, Hyon-Sob;Kim, Jae-Won;Lee, Kyeong-Jun
    • Journal of Fisheries and Marine Sciences Education
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    • v.26 no.3
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    • pp.667-675
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    • 2014
  • Two types of diets, extruded pellet (EP) and raw-fish-based moist pellet (MP) were fed to compare growth, water quality and histology of olive flounder, Paralichthys olivaceus in Jeju fish farm. Two groups of 7000 fish per each tank (initial mean weight 51 g) were fed one of two diets for 7 months. At the end of the feeding trial, significant differences were found in weight gain and feed utilization. Dissolved oxygen (DO) level of the MP tank was decreased from 7.98 to 6.89 after feeding. There were no significant differences in hematocrit, hemoglobin, alanine aminotransferase and aspartate aminotransferase of fish fed the two diets. Whole body protein content of fish fed the EP was significantly higher than that of fish fed the MP. While the feeding rate by month indicated numerically decreased, fish fed the MP had higher feed intake than that of fish fed the EP. Histological examination of hepatopancreas, kidney, and anterior intestine of fish fed the EP did not show any negative effects compared to those of fish fed the MP. This study revealed that EP could substitute for MP in terms of growth performance, blood parameters, water quality and histology of olive flounder.

Risk Stratification for Serosal Invasion Using Preoperative Predictors in Patients with Advanced Gastric Cancer

  • Park, Sung-Sil;Min, Jae-Seok;Lee, Kyu-Jae;Jin, Sung-Ho;Park, Sunhoo;Bang, Ho-Yoon;Yu, Hwang-Jong;Lee, Jong-Inn
    • Journal of Gastric Cancer
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    • v.12 no.3
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    • pp.149-155
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    • 2012
  • Purpose: Although serosal invasion is a critical predisposing factor for peritoneal dissemination in advanced gastric cancer, the accuracy of preoperative assessment using routine imaging studies is unsatisfactory. This study was conducted to identify high-risk group for serosal invasion using preoperative factors in patients with advanced gastric cancer. Materials and Methods: We retrospectively analyzed clinicopathological features of 3,529 advanced gastric cancer patients with Borrmann type I/II/III who underwent gastrectomy at Korea Cancer Center Hospital between 1991 and 2005. We stratified patients into low-(${\leq}40%$), intermediate-(40~70%), and high-risk (>70%) groups, according to the probability of serosal invasion. Results: Borrmann type, size, longitudinal and circumferential location, and histology of tumors were independent risk factors for serosal invasion. Most tumors of whole stomach location or encircling type had serosal invasion, so they belonged to high-risk group. Patients were subdivided into 12 subgroups in combination of Borrmann type, size, and histology. A subgroup with Borrmann type II, large size (${\geq}7$ cm), and undifferentiated histology and 2 subgroups with Borrmann type III, large size, and regardless of histology belonged to high-risk group and corresponded to 25% of eligible patients. Conclusions: This study have documented high-risk group for serosal invasion using preoperative predictors. And risk stratification for serosal invasion through the combination with imaging studies may collaboratively improve the accuracy of preoperative assessment, reduce the number of eligible patients for further staging laparoscopy, and optimize therapeutic strategy for each individual patient prior to surgery.

Reliability of two different presurgical preparation methods for implant dentistry based on panoramic radiography and cone-beam computed tomography in cadavers

  • Hu, Kyung-Seok;Choi, Da-Yae;Lee, Won-Jae;Kim, Hee-Jin;Jung, Ui-Won;Kim, Sung-Tae
    • Journal of Periodontal and Implant Science
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    • v.42 no.2
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    • pp.39-44
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    • 2012
  • Purpose: Special care is necessary to avoid invading important anatomic structures during surgery when presurgical planning is made based on radiographs. However, none of these types of radiography represents a perfect modality. The purpose of this study was to determine the reliability of presurgical planning based on the use of two types of radiographic image (digital panoramic radiography [DPR] and cone-beam computed tomography [CBCT]) by beginner dentists to place implants, and to quantify differences in measurements between radiographic images and real specimens. Methods: Ten fresh cadavers without posterior teeth were used, and twelve practitioners who had no experience of implant surgery performed implant surgery after 10 hours of basic instruction using conventional surgical guide based on CBCT or DPR. Two types of measurement error were evaluated: 1) the presurgical measurement error, defined as that between the presurgical and postsurgical measurements in each modality of radiographic analysis, and 2) the measurement error between postsurgical radiography and the real specimen. Results: The mean presurgical measurement error was significantly smaller for CBCT than for DPR in the maxillary region, whereas it did not differ significantly between the two imaging modalities in the mandibular region. The mean measurement error between radiography and real specimens was significantly smaller for CBCT than for DPR in the maxillary region, but did not differ significantly in the mandibular region. Conclusions: Presurgical planning can be performed safely using DPR in the mandible; however, presurgical planning using CBCT is recommended in the maxilla when a structure in a buccolingual location needs to be evaluated because this imaging modality supplies buccolingual information that cannot be obtained from DPR.