• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.107-115
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• 2017

Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation. Caffeine and ciprofloxacin were used as tool compounds to demonstrate the "fit for purpose" application of PBPK modeling and simulation for this study. Compared to caffeine, the PBPK modeling for ciprofloxacin was challenging due to several factors including solubility, permeability, clearance and tissue distribution etc. Therefore, intensive parameter sensitivity analysis (PSA) was conducted to optimize the PBPK model for ciprofloxacin. Overall, the increase in $C_{max}$ of caffeine by ciprofloxacin was not significant. However, the increase in AUC was observed and was proportional to the administered dose of ciprofloxacin. The predicted DDI and PK results were comparable to observed clinical data published in the literatures. This approach would be helpful in identifying potential key factors that could lead to significant impact on PBPK modeling and simulation for challenging compounds.

• Toxicological Research
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• v.20 no.3
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• pp.263-272
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• 2004

This study was to investigate single and repeated-dose toxicities of DFA IV, a new candidate of nutraceutical which has preventive effect on anemia and osteoporosis. In single-dose oral toxicity study, the test article were administered once by gavage to rats at dose level of 0, 2,000 and 5,000 mg/kg. No dead animal, abnormal sign and abnormal necropsy finding was found in control and treated groups. Thus the approximate lethal dose of DFA IV was considered to be higher than 5,000 mg/kg in rats. In four week repeated dose oral toxicity study, the test article was administered once daily by gavage to rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg. No abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, hematological findings, necropsy findings, organ weights and histopathological findings. In urinalysis, specific gravity was increased in 2,000 mg/kg groups of male rats. In serum biochemical analysis, creatine phosphokinase was increased in all treatment groups of male rats. These increases in urine specific gravity and serum creatine phosphokinase activity were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, four week repeated oral dose of DFA IV to rats did not cause apparent toxicological change at the dose of 500, 1,000 or 2000 mg/kg body weight. Thus it is suggested that no-observed-adverse-effect level (NOAEL) of DFA IV in rats would be 2,000 mg/kg/day body weight.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4209-4212
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• 2016

Purpose: To study clinical factors related to adequacy of transformation zone (TZ) components in cervical smears. Materials and Methods: Medical and Papanicolaou (Pap) smear reports from Thammasat University Hospital, Thailand during January to December 2015 were collected. Demographic data was reviewed by attending physicians and impact of clinical factors onTZ adequacy was primary outcome. A total of 3,251 smears were reviewed. Finally, 2,098 smears met The inclusion criteria and enrolled into this study. Results: Average age and bodyweight of participants in this study were 43.0 years and 60.0 kg, respectively. Ninety seven percent of smears were classified as satisfactory for evaluation according to the Bethesda system 2001. Adequacy (group A) and inadequacy (group B) of TZ were equal in percentage (50.9/46.0). Prevalence of abnormal cervical cytology was 4.4%. Percentages of abnormal Pap smears in group A and B were 7.3 and 1.4, respectively (p<0.001). Factors associated with increased adequacy of TZ were old-age (${\geq}50yr$), nulliparity, within 3-months postpartum, history of TZ inadequacy and abnormal smears. Sexually transmitted disease (STD), hormonal usage, previous cryotherapy and smears collected by staff were associated with inadequacy of TZ. Conclusions: Collection of cervical specimens should be carefully performed. STD history, hormonal usage and previous cryotherapy are risk factors for TZ inadequate specimens.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4977-4980
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• 2015

Background: ASC-US cases are managed according to the current American Society for Colposcopy and Cervical Pathology (ASCCP) guideline in which a human papillomavirus (HPV) test and repeat Pap smear are performed in the next 1 year. Colposcopy in cases of positive high risk HPV and persistent ASC-US or more in subsequent Pap smear is recommended. The HPV test is more expensive and still not currently a routine practice in Thailand. Objective: To identify the risk factors of persisted abnormal Pap smear and the colposcopic requirement rate in women with ASC-US. Materials and Methods: During 2008-2013, this study was conducted in Prapokklao Hospital, Chanthaburi, Thailand. Participants were women who attended gynaecology clinic for cervical cancer screening. Women who had cytological reports with ASC-US were recruited. During the study period, 503 cases were enrolled. Colposcopic requirement was defined as those who were detected with an ASC-US or more in subsequent Pap smears up to 1 year follow-up. Results: The colposcopic referral rate was 23.2 (85/365) percent at 12 months. Prevalence of cervical intraepithelial neoplasia (CIN) 2/3 was 3.3 (12/365) percent. Loss follow-up rate of subsequent Pap smear and colposcopic appointment were 27.4 (138/503) and 48.2 (41/85) percent, respectively. There was no invasive cancer. High risk factors for persisted abnormal Pap smears in subsequent test were premenopausal status, HIV infected patients and non-oral contraceptive pills (COC) users. Conclusions: Referral rate for colposcopy in women with ASC-US reports was rather high. Loss to follow-up rate was the major limitation. Immediate colposcopy should be offered for women who had high risk for silent CIN.

• Journal of Korean society of Dental Hygiene
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• v.7 no.4
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• pp.595-609
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• 2007

The purpose of this study was to classify the courses of the dental-hygiene curricula into several categories by field, to incorporate the subjects in the same category into an integrated course, and to suggest how to ensure the successful phase-in application of integrative education according to Ronald M. Harden's 11-stage integrative ladder model. The findings of the study were as follows: 1. When the existing curricula were analyzed, it's found that many credits were provided to the courses in the area of basic dentistry that offered both theory and practice. In particular, the subjects tested by the national examination were offered by every college. In the field of public oral health, the largest number of credits was allocated to theory of oral prophylaxis and practice courses. In clinical area, clinical practice, in the area of dental office management, dental insurance course was given the largest credit. There were 31 to 61 major subjects in the colleges, which indicated that the major subjects were segmented in detail. 2. It seemed necessary to incorporate the subjects in the field of basic dentistry into oral biology, and theory of oral prophylaxis/practice, preventive dentistry/practice, preclinical stage, emergency treatment and introduction to dental hygiene should be integrated in to clinical dental hygiene. The courses in clinical area should be combined into clinical dentistry, and in the field of medical management, dental insurance, hospital management and medical relation law should be incorporated into management of dental clinic. 3. In the 11-stage integrative ladder, the subjects in the same field could perfectly be incorporated as the stages advanced. Each of the subjects was less emphasized, and communication and joint plans among teachers who were respectively in charge of the courses were increasingly considered important. Specifically, there should be a consensus among the teachers in regard to the outline of teaching programs, order of education. objects and objectives of programs and what and how to evaluate.

• Proceedings of the Korean Society of Toxicology Conference
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• 1997.10a
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• pp.38-42
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• 1997

Human growth hormone is known as one of the peptide hormones which is consisted of 191 amino acids derived from the pituitary gland in humans. The objectives of this study were to supply inexpensive recombinant methionyl human growth hormones (rHGH) synthesized by the DNA technology in a yeast cell line and followed by the establishement of protein purification techniques. The next steps of the research were to study its physic-chemical properties and biological properties, and to evaluate various preclinical aspcts including pharmacokinetics sutdy, general pharmacology study, general toxicity test, and specific toxicity tests. Clinical phase I, II, III studies were also done against growth hormone dficient children to reveal that growth promoting effects were similar compared with the natural HGH extracted from pituitary glands and commercially available rHGHs. The results could be summarized that (I) this yeast dervied rHGH have had excellent physico-chemical and biological properties in comparison with a natural HGH and other synthesized rHGHs, (2) we could not see any toxic side effects when very high doses were administered to the experimental animals, and (3) this growth hormone showed effectiveness in the growth stimulating to growth hormone deficient patients.

• Journal of Periodontal and Implant Science
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• v.52 no.5
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• pp.370-382
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• 2022

Purpose: The aim of this study was to evaluate the preclinical results of 2 types of commercially available deproteinized bovine bone mineral (DBBM) when applied to alveolar bone defects in dogs. Methods: This study was conducted using 6 beagles. Alveolar defects in the mandible were formed and filled with 2 DBBMs produced by a similar procedure. Defects were randomly assigned to be filled using DBBM 1 or 2. All defects were covered with a collagen membrane and had a healing period of 12 weeks. After the dogs were sacrificed, histological, histomorphometric, and linear/volumetric analyses were performed. Results: Both DBBM groups showed similar histological findings, demonstrating that bone remodeling had occurred and new bone had formed. The residual bone particles were surrounded by newly formed vital bone. In the histomorphometric analysis, the ratio of the area of vital bone and residual bone substitute in DBBM 2 (38.18% and 3.47%, respectively) was higher than that of DBBM 1 (33.74% and 3.41%, respectively), although the difference was not statistically significant. There were also no statistically significant differences between both groups in linear and volumetric analyses using micro-computed tomography scans and digitized images of dental casts. Conclusions: In the present study, DBBM 1and 2, which were produced by similar processes, showed similar results in histological, histomorphometric, and volumetric analyses. Further studies are needed to identify more specific differences between the 2 DBBMs.

• Genomics & Informatics
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• v.19 no.3
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• pp.31.1-31.9
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• 2021

Leptospirosis is a zoonotic disease caused by spirochetes from the genus Leptospira. In Thailand, Leptospira interrogans is a major cause of leptospirosis. Leptospirosis patients present with a wide range of clinical manifestations from asymptomatic, mild infections to severe illness involving organ failure. For better understanding the difference between Leptospira isolates causing mild and severe leptospirosis, illumina sequencing was used to sequence genomic DNA in both serotypes. DNA of Leptospira isolated from two patients, one with mild and another with severe symptoms, were included in this study. The paired-end reads were removed adapters and trimmed with Q30 score using Trimmomatic. Trimmed reads were constructed to contigs and scaffolds using SPAdes. Cross-contamination of scaffolds was evaluated by ContEst16s. Prokka tool for bacterial annotation was used to annotate sequences from both Leptospira isolates. Predicted amino acid sequences from Prokka were searched in EggNOG and David gene ontology database to characterize gene ontology. In addition, Leptospira from mild and severe patients, that passed the criteria e-value < 10e^-5 from blastP against virulence factor database, were used to analyze with Venn diagram. From this study, we found 13 and 12 genes that were unique in the isolates from mild and severe patients, respectively. The 12 genes in the severe isolate might be virulence factor genes that affect disease severity. However, these genes should be validated in further study.

• Anatomy and Cell Biology
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• v.56 no.3
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• pp.313-321
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• 2023

The details of the facial nerve pattern were clearly explained in the parotid gland (PG), lateral area of the face, and periorbital areas to prevent the unexpected outcome of medical intervention. However, it remains unclear whether information about the zygomatico-buccal plexus (ZBP) in the masseteric and buccal regions. Therefore, this study aimed to help clinicians avoid this ZBP injury by predicting their common location. This study was conducted in forty-two hemifaces of twenty-nine embalmed cadavers by conventional dissection. The characteristics of the buccal branch (BB) and the ZBP were investigated in the mid-face region. The results presented that the BB gave 2-5 branches to emerge from the PG. According to the masseteric and buccal regions, the BB were arranged into ZBP in three patterns including an incomplete loop (11.9%), a single-loop (31.0%), and a multi-loop (57.1%). The mean distance and diameter of the medial line of the ZBP at the corner of the mouth level were 31.6 (6.7) and 1.5 (0.6) mm respectively, while at the alar base level were 22.5 (4.3) and 1.1 (0.6) mm respectively. Moreover, the angular nerve arose from the superior portion of the ZBP at the alar base level. The BB formed a multiloop mostly and showed a constant medial line of ZBP in an area approximately 30 mm lateral to the corner of the mouth, and 20 mm lateral to the alar base. Therefore, it is recommended that physicians should be very careful when performing facial rejuvenation in the mid-face region.

• International Journal of Stem Cells
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• v.16 no.4
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• pp.415-424
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• 2023

Therapeutic efficacy of mesenchymal stem cells (MSCs) is determined by biodistribution and engraftment in vivo. Compared to intravenous infusion, biodistribution of locally transplanted MSCs are partially understood. Here, we performed a pharmacokinetics (PK) study of MSCs after local transplantation. We grafted human MSCs into the brains of immune-compromised nude mice. Then we extracted genomic DNA from brains, lungs, and livers after transplantation over a month. Using quantitative polymerase chain reaction with human Alu-specific primers, we analyzed biodistribution of the transplanted cells. To evaluate the role of residual immune response in the brain, MSCs expressing a cytosine deaminase (MSCs/CD) were used to ablate resident immune cells at the injection site. The majority of the Alu signals mostly remained at the injection site and decreased over a week, finally becoming undetectable after one month. Negligible signals were transiently detected in the lung and liver during the first week. Suppression of Iba1-positive microglia in the vicinity of the injection site using MSCs/CD prolonged the presence of the Alu signals. After local transplantation in xenograft animal models, human MSCs remain predominantly near the injection site for limited time without disseminating to other organs. Transplantation of human MSCs can locally elicit an immune response in immune compromised animals, and suppressing resident immune cells can prolong the presence of transplanted cells. Our study provides valuable insights into the in vivo fate of locally transplanted stem cells and a local delivery is effective to achieve desired dosages for neurological diseases.