• 제목/요약/키워드: Preclinical testing

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Veterinary management protocol for non-human primates: quarantine, anesthesia, and postoperative care for mastoidectomy at animal research institutions

  • Yoon Beom Lee;Woori Jo;Eui-Suk Jeong;Tae Ku Kang;Gwang-Hoon Lee
    • 대한수의학회지
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    • 제63권4호
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    • pp.35.1-35.10
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    • 2023
  • Non-human primate (NHP) research faces challenges due to zoonosis risk and complex veterinary management yet lacks standardized guidelines for animal care. Therefore, we developed an advanced veterinary management protocol for NHP quarantine, anesthesia, and postoperative care. Three female 4 to 5-year-old cynomolgus monkeys were anesthetized and underwent various tests, including body weight, temperature, blood tests, urinalysis, microbiological monitoring, and physical and dental examinations. Ivermectin and medicated baths were administered to eradicate ectoparasites and endoparasites, and testing was repeated 30 days later. Following quarantine, we performed computed tomography and anesthesia maintenance for mastoidectomy. To relieve pain and maintain body weight, we administered tramadol intramuscularly 4 times/day for 3 days and meloxicam subcutaneously twice daily for 14 days. Feed replacements were provided. During the 33-day quarantine period, physical examinations revealed no abnormalities indicative of infectious diseases, and no specific clinical symptoms were observed. Through a preliminary test of anesthesia time, we selected ketamine 4 mg/kg + medetomidine 50 ㎍/kg for short experiments such as computed tomography, and ketamine 8 mg/kg + medetomidine 50 ㎍/kg for intubation. Ten days after mastoidectomy, NHPs consumed 100 kcal/kg and recovered their body weight. This study offers advanced veterinary management guideline for NHP research. Such protocols can lead to more standardized and ethical practices in NHP research, thereby enhancing the quality of studies on NHPs and the translation of findings to human health and disease.

Strong concordance between RNA structural and single nucleotide variants identified via next generation sequencing techniques in primary pediatric leukemia and patient-derived xenograft samples

  • Barwe, Sonali P.;Gopalakrisnapillai, Anilkumar;Mahajan, Nitin;Druley, Todd E.;Kolb, E. Anders;Crowgey, Erin L.
    • Genomics & Informatics
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    • 제18권1호
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    • pp.6.1-6.9
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    • 2020
  • Acute leukemia represents the most common pediatric malignancy comprising diverse subtypes with varying prognosis and treatment outcomes. New and targeted treatment options are warranted for this disease. Patient-derived xenograft (PDX) models are increasingly being used for preclinical testing of novel treatment modalities. A novel approach involving targeted error-corrected RNA sequencing using ArcherDX HemeV2 kit was employed to compare 25 primary pediatric acute leukemia samples and their corresponding PDX samples. A comparison of the primary samples and PDX samples revealed a high concordance between single nucleotide variants and gene fusions whereas other complex structural variants were not as consistent. The presence of gene fusions representing the major driver mutations at similar allelic frequencies in PDX samples compared to primary samples and over multiple passages confirms the utility of PDX models for preclinical drug testing. Characterization and tracking of these novel cryptic fusions and exonal variants in PDX models is critical in assessing response to potential new therapies.

Drug Safety Evaluation in the United States of America

  • Yoon, Young-H.;Johnson, Charles A.;Soltys, Randolph A.;Sibley, Peter L.
    • 한국수의병리학회지
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    • 제1권2호
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    • pp.91-96
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    • 1997
  • General steps in the discovery and development of novel drugs in the United States are presented. The first step is the discovery of novel drugs. Brief histories and mechanisms of a few novel drugs in the American market are outlined. In this presentation preclinical animal toxicologic studies (drug safety evaluateion) are emphasized in regard to drug development. When preclinical animal studies have defined the toxicity and the doses at which it occurs an Investigational new Drug Application (IND) is submitted to the Food and Drug Administration (FDA) An IND notifies the FDA the intention to begin testing a novel drug in human subjects.

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Review of the UBC Porcine Model of Traumatic Spinal Cord Injury

  • Kim, Kyoung-Tae;Streijger, Femke;Manouchehri, Neda;So, Kitty;Shortt, Katelyn;Okon, Elena B.;Tigchelaar, Seth;Cripton, Peter;Kwon, Brian K.
    • Journal of Korean Neurosurgical Society
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    • 제61권5호
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    • pp.539-547
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    • 2018
  • Traumatic spinal cord injury (SCI) research has recently focused on the use of rat and mouse models for in vivo SCI experiments. Such small rodent SCI models are invaluable for the field, and much has been discovered about the biologic and physiologic aspects of SCI from these models. It has been difficult, however, to reproduce the efficacy of treatments found to produce neurologic benefits in rodent SCI models when these treatments are tested in human clinical trials. A large animal model may have advantages for translational research where anatomical, physiological, or genetic similarities to humans may be more relevant for pre-clinically evaluating novel therapies. Here, we review the work carried out at the University of British Columbia (UBC) on a large animal model of SCI that utilizes Yucatan miniature pigs. The UBC porcine model of SCI may be a useful intermediary in the pre-clinical testing of novel pharmacological treatments, cell-based therapies, and the "bedside back to bench" translation of human clinical observations, which require preclinical testing in an applicable animal model.

호흡기계 표준화 환자를 이용한 간호대 학생의 임상수행능력평가 타당도와 신뢰도 검증 (Validity and Reliability of a Clinical Performance Examination using Standardized Patients)

  • 최자윤;장금성;최순희;홍미순
    • 대한간호학회지
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    • 제38권1호
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    • pp.83-91
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    • 2008
  • Purpose: The purpose of this study was to test the validity of a modified clinical performance examination (CPX) for preclinical students in nursing. Method: 70 nursing students in their second semester of the junior year at C University participated in CPX. Scenarios and checklists were developed by our research team from September to October 2005. Six stations were organized. Evaluation included physical examination of a patient with lung cancer, education on usage of a metered dosage inhaler, and lobectomy postoperative care. Students were randomly assigned to a station. Result: There was a difference in the CPX scores according to stations. The agreement of scoring between trained faculty members and SPs was more than moderate (r=.647). The correlation between the CPX score and the average grade in the previous semester and between the CPX score and the average grade of a paper and pen test of the pulmonary system of adults was low (r=.276; r=.048). Conclusion: Traditional CPX is generally recommended, however, modified CPX is appropriate for preclinical students in the current Korean Nursing school setting if there are additional scoring systems to balance the testing level at each station.

Mean Sojourn Time of Preclinical Gastric Cancer in Korean Men: A Retrospective Observational Study

  • Bae, Jong-Myon;Shin, Sang Yop;Kim, Eun Hee
    • Journal of Preventive Medicine and Public Health
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    • 제47권4호
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    • pp.201-205
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    • 2014
  • Objectives: This retrospective cohort study aimed to estimate the mean sojourn time (MST) of preclinical gastric cancer in Korean men. Methods: The subjects consisted of voluntary male screenees aged 40 to 69 years who underwent subsequent screening gastroscopies after testing negative at a baseline screening performed between January 2007 and December 2011. A new case was defined if gastric cancer cells were present in the biopsy specimens obtained from gastroscopy. The follow-up period was calculated as the number of person-years between the date of baseline screening gastroscopy and positive findings at a subsequent screening. The MST was calculated using transition rates of gastric cancer to determine the best screening interval. Results: Of the 171 979 voluntary male screenees, 61 688 (36%) underwent subsequent screening gastroscopies between January 2007 and December 2011. A total of 91 incident cases were found during 19 598 598 person-years of follow-up. The MST of gastric cancer was 2.37 years (95% confidence intervals, 1.92 to 2.96), and those aged 40 to 49 years had a shorter MST than those 50 to 69 years did. Conclusions: These findings support the 2-year interval of screening recommended by the nationwide gastric cancer screening program in Korea. Further studies for the age-specific MST among women are needed.

CPC-222, A New Fluoroquinolone

  • Lee, Younha
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1997년도 춘계학술대회
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    • pp.12-12
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    • 1997
  • CFC-222 is a novel fluoroqinolone antibacterial agent synthesized and under development by the Cheil Jedang Corporation, Korea. CFC-222 exerts the antibacterial activity by inhibition of bacterial DNA gyrase leading to bactericidal action. In in vitro and in vivo preclinical testing, CFC-222 has been shown to possess a broad spectrum of antibacterial activity. In particular CFC-222 is very potent against Gram-positive bacteria such as Staphylococcus spp., Streptocuccus spp. (in particular penicillin G-resistant and -susceptible S. pneumoniae) and Enterococcus spp. when compared to other quinolones (ciprofloxacin, ofloxacin or lomefloxacin). CFC-222 also showed potent activity against the methicillin resistant clinical isolates of S. aureus (MRSA). Against Gram-negative bacteria (E. coli, Pseudomonas and Sarcina) the activity of CFC-222 was slightly weaker than that of ciprofloxacin, but was more potent than that of ofloxacin or lomefloxacin. In urinary systemic infections caused by both Gram-positive and -negative bacteria, CFC-222 demonstrated a potent therapeutic efficacy in particular against Cram-positive bacteria S. aureus, S. pyrogen 203 and S. pneumonia TypeIII.

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Use of in vitro assays for evaluating physiological functionality of foods: General consideration

  • Chun Hyang Sook
    • 한국식품영양과학회:학술대회논문집
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    • 한국식품영양과학회 2003년도 정기총회 및 54차 학술발표회:건강기능식품의 유효성평가
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    • pp.74-77
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    • 2003
  • A new health paradigm may be evolving that would place emphasis on the positive aspects of diet, identifying components that are physiologically active and that contribute to the prevention of disease onset. It has been increasingly difficult to evaluate the impact of new bioactive materials and food products on the well being of society. Thus, testing systems for both health function and toxicity have become very elaborate, complex, and interrelated, making their interpretation difficult and open to controversy. To select the proper starting materials, to screen the appropriate health functionality and to determine the efficacy of product, a reliable, reproducible, sensitive and predictive assay is required. Particularly, in uitro assay is the first stage in preclinical test on physiologically active materials and have many advantages in terms of time, cost and convenience. However, several factors as well as some limitations should be considered in this assay system. This presentation, therefore, will address the use of in uitro assays for evaluating physiological functionality of foods coupled with general consideration.

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Clinical application of genome-wide single nucleotide polymorphism genotyping and karyomapping for preimplantation genetic testing of Charcot-Marie-Tooth disease

  • Kim, Min Jee;Park, Sun Ok;Hong, Ye Seul;Park, Eun A;Lee, Yu Bin;Choi, Byung-Ok;Lee, Kyung-Ah;Yu, Eun Jeong;Kang, Inn Soo
    • Journal of Genetic Medicine
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    • 제19권1호
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    • pp.7-13
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    • 2022
  • Purpose: Preimplantation genetic testing for monogenic disorders (PGT-M) has been successfully used to prevent couples with monogenic disorders from passing them on to their child. Charcot-Marie-Tooth Disease (CMT) is a genetic disorder characterized by progressive extremity muscle degeneration and loss of sensory function. For the first time in Korea, we report our experience of applying single nucleotide polymorphism genotyping and karyomapping for PGT-M of CMT disease. Materials and Methods: Prior to clinical PGT-M, preclinical tests were performed using genotypes of affected families to identify informative single-nucleotide polymorphisms associated with mutant alleles. We performed five cycles of in vitro fertilization PGT-M in four couples with CMT1A, CMT2A, and CMT2S in CHA Fertility Center, Seoul Station. Results: From July 2020 through August 2021, five cycles of PGT-M with karyomapping in four cases with CMT1 and CMT2 were analyzed retrospectively. A total of 17 blastocysts were biopsied and 15 embryos were successfully diagnosed (88.2%). Ten out of 15 embryos were diagnosed as unaffected (66.7%). Five cycles of PGT-M resulted in four transfer cycles, in which four embryos were transferred. Three clinical pregnancies were achieved (75%) and the prenatal diagnosis by amniocentesis for all three women confirmed PGT-M of karyomapping. One woman delivered a healthy baby uneventfully and two pregnancies are currently ongoing. Conclusion: This is the first report in Korea on the application of karyomapping in PGT-M for CMT patients. This study shows that karyomapping is an efficient, reliable and accurate diagnostic method for PGT-M in various types of CMT diseases.

Silent High Grade Cervical Intraepithelial Neoplasia in Atypical Smears from Liquid Based Cervical Cytology - Three Years Experience in Thammasat University Hospital

  • Lertvutivivat, Supapen;Chanthasenanont, Athita;Muangto, Teerapat;Nanthakomon, Tongta;Pongrojpaw, Densak;Bhamarapravatana, Kornkarn;Suwannarurk, Komsun
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권9호
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    • pp.4353-4356
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    • 2016
  • Purpose: To study the prevalence of CIN2+ diagnosis in women with atypical Papaniculoau (Pap) smears to suggest appropriate management option for Thai health care. Materials and Methods: Data from all patients with liquid based cytology with human papillomavirus (HPV) testing between May 2013 - May 2016 were collected from medical records. Women with atypical cervical Pap smears were recruited. Results for age, HPV testing, HPV 16, 18, 45 and other genotypes tested, colposcopic examination and histopathological assessment were all collected. Atypical smears were defined as atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells cannot be exclude high grade squamous intraepithelial lesion (ASC-H). Results: A total of 2,144 cases were recruited. Twenty six women with ASC-US on cytology had high risk (HR) HPV detection while eight cases with ASC-H had HR-HPV (40.0% VS 72.7%, p=0.005). Among the 26 women with ASC-US cytology and positive HR-HPV, HPV type 16 (n=8, 30.8%), type 18 (n=1, 3.8%), type 45 (n=1, 3.8%) and other HPV types (n=17, 65.4%) were found. Eight women with ASC-H and positive HR-HPV demonstrated type 16 (n=6, 75%) and other HPV types (n=2, 25%). Fifty seven women with ASC-US had normal colposcopy, CIN1 and CIN2+ at percentages of 80.7 (46/57), 14.0 (8/57) and 5.3 (3/57), respectively. In the ASC-H group, 7 out of 10 women had normal colposcopy and three (30%) had CIN2+ results. Conclusions: In women with ASC-US cytology, immediate colposcopy is highly recommended. HPV testing can be performed if colposcopy is not an available option because there was high prevalence (5.3%) of CIN2+ in our findings. ASCCP recommendations for ASC-H that colposcopy should be performed on all ASC-H cases regardless of HPV result are thereby supported by the findings of this investigation.