• Title/Summary/Keyword: Preclinical Study

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Investigation of Immune Biomarkers Using Subcutaneous Model of M. tuberculosis Infection in BALB/c Mice: A Preliminary Report

  • Husain, Aliabbas A.;Daginawala, Hatim F.;Warke, Shubangi R.;Kalorey, Devanand R.;Kurkure, Nitin V.;Purohit, Hemant J.;Taori, Girdhar M.;Kashyap, Rajpal S.
    • IMMUNE NETWORK
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    • v.15 no.2
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    • pp.83-90
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    • 2015
  • Evaluation and screening of vaccines against tuberculosis depends on development of proper cost effective disease models along with identification of different immune markers that can be used as surrogate endpoints of protection in preclinical and clinical studies. The objective of the present study was therefore evaluation of subcutaneous model of M.tuberculosis infection along with investigation of different immune biomarkers of tuberculosis infection in BALB/c mice. Groups of mice were infected subcutaneously with two different doses : high ($2{\times}10^6CFU$) and low doses ($2{\times}10^2CFU$) of M.tuberculosis and immune markers including humoral and cellular markers were evaluated 30 days post M.tuberculosis infections. Based on results, we found that high dose of subcutaneous infection produced chronic disease with significant (p<0.001) production of immune markers of infection like $IFN{\gamma}$, heat shock antigens (65, 71) and antibody titres against panel of M.tuberculosis antigens (ESAT-6, CFP-10, Ag85B, 45kDa, GroES, Hsp-16) all of which correlated with high bacterial burden in lungs and spleen. To conclude high dose of subcutaneous infection produces chronic TB infection in mice and can be used as convenient alternative to aerosol models in resource limited settings. Moreover assessment of immune markers namely mycobacterial antigens and antibodies can provide us valuable insights on modulation of immune response post infection. However further investigations along with optimization of study protocols are needed to justify the outcome of present study and establish such markers as surrogate endpoints of vaccine protection in preclinical and clinical studies in future.

Genotoxicity and Interference with Cell Cycle Activities by an Ethanolic Extract from Thai Plumbago indica Roots in Human Lymphocytes in vitro

  • Thitiorul, Sumon;Ratanavalachai, Treetip;Tanuchit, Sermkiat;Itharat, Arunporn;Sakpakdeejaroen, Intouch
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2487-2490
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    • 2013
  • In Thai traditional medicine, Plumbago indica or Jetamul-Pleung-Dang in Thai is known to have health benefit especially for anti-inflammatory, antibacterial, and antitumor activities. However, the mechanisms of its action are still uncertain. One of which might be genotoxic effects. In the present study, we investigated the genotoxicity of an ethanolic extract of Plumbago indica root (EEPIR) by sister chromatid exchange (SCE) assay in human lymphocytes. Results have shown that all treatments with EEPIR ($12.5-100{\mu}g/ml$) could induce cell cycle delay as shown by significant increase in the number of metaphase cells in the first cell cycle but neither in the second nor the third cell cycle. Only at concentrations of 25, 50, and $100{\mu}g/ml$ were SCE levels significantly increased above that of the control (p<0.05). EEPIR at a concentration of $500{\mu}g/ml$ induced cell death as few mitotic cells were shown. Accordingly, EEPIR ($25-100{\mu}g/ml$) is genotoxic in human lymphocytes and cytotoxic at concentrations of ${\geq}500{\mu}g/ml$ in vitro. Therefore, these activities of the EEPIR could serve its potential therapeutic effects, especially as an anticancer agent. Further study of EEPIR in vivo is now needed to support this in vitro evidence.

The Effects of Preclinical Objective Structured Clininal Examination(OSCE) on Knowledge, Nursing Students Confidence in Core Fundamental Nursing Skills and Self-Efficacy (임상실습 전 객관화된 구조화 임상수행평가(OSCE)가 간호대학생의 지식, 핵심기본간호술 자신감 및 자기효능감에 미치는 효과)

  • Son, Yu-Lim;Park, Pil-Nam;Ko, Soon-Hee
    • Journal of Korean Clinical Health Science
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    • v.5 no.2
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    • pp.850-863
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    • 2017
  • Purpose. The purpose of this study was to investigate effects of preclinical OSCE(Objective Structured Clinical Evaluation) on knowledge, confidence in their Core fundamental nursing skills and self-efficacy in nursing students. Method. The research design was a one group pretest-posttest design and it was done to assess changes in knowledge, confidence in core fundamental nursing skills and self-efficacy from pre to the post-test which was given after the OSCE. Data were collected from March 5 to April 7, 2016 from 37 nursing students who were taking the 15-hours using OSCE learning module at one Gyeongbuk-do, P-city. This practicum was composed of 4 core fundamental nursing skills and 5 other fundamental nursing skills. The knowledge consisted of a 10-item by researchers and the confidence of core fundamental nursing skills consisted of an 9-item NRS and the self-efficacy consisted of a 17-item 5-point scale and measured in both the pretest and posttest. The collected data were analyzed with SPSS IBM 20.0 program for the frequency, percentage, x2-test, and paired t-test. Rusult. The results showed that although scores of knowledge of OSCE learning module were significanlty increased from 5.22 to 7.03(t=5.30, p<.001). There were significantly increased in scores of confidence in core fundamental nursing skills from 5.13 to 7.27(t=10.01, p<.001), In the sub-scales of each core fundamental nursing skills was scored the highest. otherwise, there was no significant difference in self-efficacy(t=1.42, p=.161). Conclusions. Based on the results, this study suggests that OSCE module development activities for nursing students in nursing education-learning in order to improve nursing skills.

Evaluation of Process and Satisfaction for Selective Courses in a Medical School (의과대학 선택교육과정의 운영절차와 만족도 평가)

  • Kim, Do-Hwan;Choi, Young-Hyu;Han, Sang Yun;Shin, Jwa-Seop;Lee, Seunghee
    • Korean Medical Education Review
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    • v.19 no.2
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    • pp.90-100
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    • 2017
  • The necessity of embracing selective courses in medical curriculum is increasing due to the expansion of medical knowledge and changes in the health care environment. In contrast to the abundant evidence regarding elective or selective courses during the clinical phase, articles focusing on the preclinical period are relatively scarce. This study aims to explore the development, implementation, and evaluation of newly-adopted selective courses in the first-year medical curriculum in a medical school which recently underwent a major curricular revision. First of all, the Curriculum Committee established goals and operating principles of the courses, and then the committee encouraged all participating professors to attend a related faculty development workshop after finalizing the list of courses. A survey was conducted at the end of each course for evaluation. Of the 36 courses opened in 2016, the overall satisfaction of students was $4.98{\pm}1.06$ (out of 6) and showed a strong correlation with students' previous expectations, reasoning- and participation-oriented teaching, and outcome of the courses including increased motivation. In the open-ended responses, students and professors described not only intended outcomes such as acquisition of medical knowledge and increased interest in new topics, but also unintended outcomes including positive impression for selective courses and even high satisfaction and rewarding experiences, especially from the teachers' perspective. Although long-term outcomes remain to be seen, the results of this study show the feasibility and impact of selective courses and will contribute to effective implementation in other medical schools.

Lack of Association of the Cyclooxygenase-2 Gene 8473T>C Polymorphism with Breast Cancer Risk: a Meta-analysis

  • Yang, Xi;Zhao, Fen;Li, Yue-Hua;Huang, Min;Huang, Ying;Yi, Cheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9693-9698
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    • 2014
  • Background: Associations between the 8473T>C polymorphism (rs5275) in the cyclooxygenase-2 (COX-2) gene and breast cancer (BC) risk are still inconclusive and ambiguous. The aim of this meta-analysis was to comprehensively estimate the genetic risk of 8473T>C polymorphism in the COX-2 gene for BC. Materials and Methods: We searched PubMed, Web of Science, Medline, Chinese biomedical (CBM), Weipu, China national knowledge infrastructure (CNKI), and Wanfang databases, covering all publications (last search was updated on Aug 17, 2014). Statistical analyses were performed using Revman 5.3 and STATA 10.0 software. Results: A total of 6,720 cases and 9,794 controls in 12 studies were included in this study. The results indicated no significant associations between the 8473T>C polymorphism of the COX-2 gene and BC risk for the CC+TC vs TT model (pooled odds ratio (OR)=0.97, 95% confidence interval (CI)=0.90-1.03, and p=0.29). On subgroup analysis, we also found that subdivision on ethnicity among Caucasians, Asians and others also revealed no relationship with BC susceptibility. With the study design (CC+TC vs TT), no significant associations were found in either population-based case-control studies (PCC), or hospital-based case-control studies (HCC). Conclusions: This present meta-analysis suggests that the 8473T>C polymorphism in the COX-2 gene is not a conspicuous low-penetrant risk factor for developing BC.

Changes in Breast-tumor Blood Flow in Response to Hypercapnia during Chemotherapy with Laser Speckle Flowmetry

  • Kim, Hoonsup;Lee, Youngjoo;Lee, Songhyun;Kim, Jae Gwan
    • Current Optics and Photonics
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    • v.3 no.6
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    • pp.555-565
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    • 2019
  • Development of a biomarker for predicting tumor-treatment efficacy is a matter of great concern, to reduce time, medical expense, and effort in oncology therapy. In a preclinical study, we hypothesized that the blood-flow parameter based on laser speckle flowmetry (LSF) could be a potential indicator to estimate the efficacy of breast-cancer treatment. To verify this hypothesis, a 13762-MAT-B-III rat breast tumor was grown in a dorsal skinfold window chamber applied to a nude mouse, and the change in blood flow rate (BFR) - or the speckle flow index (SFI) is used together as the same meaning in this manuscript - was longitudinally monitored during tumor growth and metronomic cyclophosphamide treatment. Based on the daily LSF angiogram, several BFR parameters (baseline SFI, normalized SFI, and △rBFR) were compared to tumor size in the normal, treated, and untreated tumor groups. Despite the incomplete tumor treatment, we found that the daily changes in all BFR parameters tended to have partially positive correlation with tumor size. Moreover, we observed that the changes in baseline SFI and normalized SFI responded one day earlier than the tumor shrinkage during chemotherapy. However, daily variations in the hypercapnia-induced △rBFR lagged tumor shrinkage by one day. This study would contribute not only to evaluating tumor vascular response to treatment, but also to monitoring blood-flow-mediated diseases (in brain, skin, and retina) by using LSF in preclinical settings.

Lack of Metformin Effects on Different Molecular Subtypes of Breast Cancer under Normoglycemic Conditions: An in vitro Study

  • Sadighi, Sanambar;Amanpour, Saeid;Behrouzi, Bita;Khorgami, Zhinoos;Muhammadnejad, Samad
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2287-2290
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    • 2014
  • Background: In the past few years, a considerable number of preclinical studies have been proposed metformin as a potential anticancer agent, but some of these studies suffer from a number of methodological limitations such as assessment of cytotoxicity in the presence of supraphysiological glucose concentrations or applying suprapharmacological levels of the drug. These objections have limited the translation of published preclinical data to the clinical setting. The present study aimed to investigate direct anticancer effects of metformin on different molecular subtypes of breast cancer with pharmacological concentrations and under normoglycemic conditions in vitro. Materials and Methods: Breast cancer cell lines from luminal A, luminal B, ErbB2 and triple-negative molecular subtypes were treated with a pharmacological concentration of metformin (2mM) at a glucose concentration of 5.5mM. Time-dependant cell viability was assessed by dye exclusion assay. MTTbased cytotoxicity assays were also performed with metformin alone or in combination with paclitaxel. Results: Metformin did not show any growth inhibitory effects or time-dependant cytotoxicity on breast cancer cell lines in the presence of normal glucose concentrations at the therapeutic plasma level. No augmentation of the antineoplastic properties of paclitaxel was apparent under the tested conditions. Conclusions: Metformin is probably unable to exert cytotoxic or cytostatic effects on breast cancer subtypes at pharmacological concentrations and normal plasma glucose levels. These results highlight the importance of establishing a higher steady-state plasma concentration of metformin in the clinical setting for assessment of anticancer effects in normoglycemic patients.

2-Week repeated oral dose toxicity study of 1,4-dichlorobutane in rats (1,4-Dichlorobutane의 랫드 2주 반복경구투여독성시험)

  • Kim, Jong-Kyu;Lee, In-Chul;Kim, Sung-Hwan;Baek, Hyung-Seon;Bae, Jin-Sook;Song, Si-Whan;Kim, Jong-Choon;Chung, Yong-Hyun
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.23 no.1
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    • pp.1-10
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    • 2013
  • Objectives: The present study investigated the potential subacute toxicity of 1,4-dichlorobutane (1,4-DCB) by a 2-week repeated oral dose in male Sprague-Dawley rats. Materials and Methods: The test chemical was administered once daily by gavage to male rats at dose levels of 0, 74, 222, 667, and 2000 mg/kg/day for 2 weeks. All rats were sacrificed at the end of treatment period. During the test period, clinical signs, mortality, body weights, food and water consumption, urinalysis, hematology, serum biochemistry, gross findings, and organ weights were examined. Results: At 2000 mg/kg/day, treatment-related clinical signs, as evidenced by hypothermia, decreased locomotor activity, piloerection, lying on side, and prone position were observed. All the rats were found dead on test day 2. At 667 mg/kg/day, polyuria, suppressed body weight gain, food consumption, and spleen and thymus weights, and increased adrenal gland and liver weights were observed.Hematological and serum biochemical investigations revealed increases in the alanine aminotransferase, alkaline phosphataseand total bilirubinand decreases in the serum $Na^+$ level, white blood cell count and lymphocyte ratio. There were no treatment-related adverse effects in the 74 and 222 mg/kg/day groups. Conclusions: In the present experimental conditions, target organs were determined to be spleen, thymus,and liver. The no-observed-adverse-effect level was considered to be 222 mg/kg/day in male rats.

Suggestions for Potentially Useful Herbal Medicines for Treating Insomnia in COVID-19 Era: A Mini-Review

  • Suh, Hyo-Weon;Kwon, Chan-Young;Kim, Jong Woo
    • Journal of Oriental Neuropsychiatry
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    • v.32 no.2
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    • pp.95-109
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    • 2021
  • Objectives: The coronavirus disease 2019 (COVID-19) has become a global pandemic. Mental sequelae occurring in patients with COVID-19 and the general population are important concerns. In Korea, herbal medicine is used nationwide to respond to this pandemic. It can be prescribed by COVID-19 telemedicine center of Korean medicine (KM). Among some herbal medicines, Gamiguibi-tang is the only herbal medicine prescribed for individuals with mental health, especially for those with insomnia. In this mini-review, the objective of this study was to summarize the evidence of some promising herbal medicines available for treating primary insomnia based on existing clinical and preclinical studies. Methods: A research team was formed for KM clinical practice guidelines for insomnia (version 1.0). Team members were provided with a list of references of relevant herbal medicines for insomnia. To gather evidence from clinical studies with appropriate sample sizes, among the list of references, randomized controlled trials for primary insomnia that included 50 subjects or more per arm and used herbal medicine were included in the final analysis. Moreover, pre-clinical studies examining the mechanism of action of each herbal medicine and studies on herb-drug interactions, were searched and summarized. Results: Four herbal medicines (Ondam-tang, Sanjoin-tang, Guibi-tang, and Hyeolbuchugeo-tang) were reviewed based on existing clinical and preclinical studies. Based on findings of existing studies, some suggestions of herbal medicines for insomnia in the COVID-19 era in Korea were suggested. Conclusions: Data of this study could be used to prepare a future revision of the manual of COVID-19 telemedicine center of KM.

Preclinical evaluation using functional SPECT imaging of 123I-metaiodobenzylguanidine (mIBG) for adrenal medulla in normal mice

  • Yiseul Choi;Hye Kyung Chung;Sang Keun Woo;Kyo Chul Lee;Seowon Kang;Seowon Kang;Joo Hyun Kang;Iljung Lee
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.7 no.2
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    • pp.93-98
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    • 2021
  • meta-iodobenzylguanidine is one of the norepinephrine analogs and reuptakes together with norepinephrine with norepinephrine transporter. The radioiodinated ligand, 123I-meta-iodobenzylguanidine, is the most widely used for single photon emission computed tomography imaging to diagnose functional abnormalities and tumors of the sympathetic nervous system. In this study, we performed cellular uptake studies of 123I-meta-iodobenzylguanidine in positive- and negative-norepinephrine transporter cells in vitro to verify the uptake activity for norepinephrine transporter. After 123I-meta-iodobenzylguanidine was injected via a tail vein into normal mice, Single photon emission computed tomography/computed tomography images were acquired at 1 h, 4 h, and 24 h post-injection, and quantified the distribution in each organ including the adrenal medulla as a norepinephrine transporter expressing organ. In vitro cell study showed that 123I-meta-iodobenzylguanidine specifically uptaked via norepinephrine transporter, and significant uptake of 123I-meta-iodobenzylguanidine in the adrenal medulla in vivo single photon emission computed tomography images. These results demonstrated that single photon emission computed tomography imaging with 123I-meta-iodobenzylguanidine were able to quantify the biodistribution in vivo in the adrenal medulla in normal mice.