• Title/Summary/Keyword: Preclinical

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Drug Safety Evaluation in the United States of America

  • Yoon, Young-H.;Johnson, Charles A.;Soltys, Randolph A.;Sibley, Peter L.
    • Korean Journal of Veterinary Pathology
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    • v.1 no.2
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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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Purification and Characterization of a New κ-Carrageenase from the Marine Bacterium Vibrio sp. NJ-2

  • Zhu, Benwei;Ning, Limin
    • Journal of Microbiology and Biotechnology
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    • v.26 no.2
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    • pp.255-262
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    • 2016
  • The carrageenan-degrading marine bacterium Vibrio sp. strain NJ-2 was isolated from rotten red algae, and κ-carrageenase with high activity was purified from the culture supernatant. The purified enzyme with molecular mass of 33 kDa showed the maximal activity of 937 U/mg at 40℃ and pH 8.0. It maintained 80% of total activity below 40℃ and between pH 6.0 and 10.0. The kinetics experiment showed the Km and Vmax values were 2.54 g/ml and 138.89 mmol/min/mg, respectively. The thin layer chromatography and ESI-MS analysis of hydrolysates indicated that the enzyme can endolytically depolymerize the κ-carrageenan into oligosaccharides with degrees of depolymerization of 2-8. Owing to its high activity, it could be a valuable tool to produce κ-carrageenan oligosaccharides with various biological activities.

Augmented Reality Technology-based Dental Radiography Simulator for Preclinical Training and Education on Dental Anatomy

  • Gu, Ja-Young;Lee, Jae-Gi
    • Journal of information and communication convergence engineering
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    • v.17 no.4
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    • pp.274-278
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    • 2019
  • It is important that students are provided opportunities to practice their skills in acquiring radiographic images. However, these opportunities are currently limited because of the risk of radiation exposure. To overcome this limitation, a new augmented reality-based radiography simulator was developed that enables students to practice radiographic techniques as part of self-directed learning without time and space constraints. Subsequently, cross-sectional images of a manikin phantom head obtained via computed tomography were reconstructed into a three-dimensional object. An image marker that could be recognized by a mobile device and could allow users to practice dental radiography techniques was devised. The three-dimensional object was augmented to the mobile device; consequently, among 106 stored dental radiographs on the device, a radiograph corresponding to specific imaging conditions was opened when users performed radiographic procedures. This technology could improve dental students' understanding of dental anatomy and contribute to improving their competency in acquiring dental radiographs.

A Brief Review of Preclinical Researches and Clinical Trials of Oxytocin on Behavior-Related Phenotypes in Prader-Willi Syndrome

  • Kim, Jiyeon
    • Journal of mucopolysaccharidosis and rare diseases
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    • v.5 no.1
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    • pp.39-41
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    • 2021
  • Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder of hyperphagia leading to severe obesity, intellectual deficits, compulsivity, and other behavioral problems. PWS is caused by the inactivation of contiguous genes on chromosome 15q11-q13, which complicates the development of targeted, effective therapeutics. Various preclinical studies have been conducted by developing mouse models that exhibit phenotypes similar to PWS. Oxytocin deficiency in PWS is associated with hyperphagia with impaired satiety and, food-seeking and behavior disorders. Here, we summarize the oxytocin study of ingestion behavior tested in the PWS mouse model and published data from clinical trials that have evaluated treatment effectiveness on ingestion behavior and social dysfunction in patients with PWS.

Novel Therapeutic Approaches to Mucopolysaccharidosis Type III

  • Yang, Aram
    • Journal of mucopolysaccharidosis and rare diseases
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    • v.5 no.1
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    • pp.22-28
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    • 2021
  • Mucopolysaccharidosis type III (MPS III) or Sanfilippo disease is an orphan-inherited lysosomal storage disease. It is one of the most common MPS subtypes. The classical presentation is an infantile-onset neurodegenerative disease characterized by intellectual regression, behavioral and sleep disturbances, loss of ambulation, and early death. Unlike other MPS, no disease-modifying therapy has been approved. Here, we review the curative therapy developed for MPS III, from historically ineffective hematopoietic stem cell transplantation and substrate reduction therapy to the promising enzyme replacement therapy or adeno-associated/lentiviral vector-mediated gene therapy. Preclinical studies are presented with recent translational first-in-man trials. We also present experimental research with preclinical mRNA and gene-editing strategies. Lessons from animal studies and clinical trials have highlighted the importance of early therapy before extensive neuronal loss. Disease-modifying therapy for MPS III will likely mandate the development of new early diagnosis strategies.

A study on the comparison of preclinical and post-training satisfaction of dental technology students in COVID-19 (코로나19 상황에서 치기공과 학생들의 임상실습 전 기대도 및 실습 후 만족도 비교에 관한 연구)

  • Hwang, Jae-Sun
    • Journal of Technologic Dentistry
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    • v.44 no.2
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    • pp.38-46
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    • 2022
  • Purpose: This study aims to confirm the effect of clinical practice on dental technology students by comparing preclinical expectations and post-training satisfaction of dental technology students in Suwon-si, Gyeonggi-do during the coronavirus disease pandemic. Methods: This study included students enrolled in the Department of Dental Technology of D University in Suwon-si, Gyeonggi-do. The purpose of the study was explained in advance and 70 students agreed to participate in the survey. IBM SPSS Statistics version 18.0 was used for data analysis and the significance level was tested at p=0.05. Results: There were significant differences in clinical practice content, operation, institutional expectations, and satisfaction. Conclusion: Based on the differences in expectations and satisfaction in this study, schools, industries, and associations can study ways to increase satisfaction in terms of clinical practice content, operation, and institution to present directions for dental technology and clinical practice.

Monitoring Differences in Vaginal Hemodynamic and Temperature Response for Sexual Arousal by Different Anesthetic Agents Using an O ptical Probe

  • Jeong, Hyeryun;Seong, Myeongsu;Park, Kwangsung;Kim, Jae Gwan
    • Current Optics and Photonics
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    • v.4 no.1
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    • pp.57-62
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    • 2020
  • The selection of anesthetic agent is important in preclinical studies, since each agent affects the systemic hemodynamics in different ways. For that reason, we hypothesized that different anesthetic agents will result in different vaginal hemodynamic response and temperature during sexual arousal, in an animal model. To validate the hypothesis, animal experiments were performed using female rats with two anesthetic agents widely used in preclinical studies: ketamine and isoflurane. Our previously developed near-infrared-spectroscopy-based probe was used to measure the changes of oxyhemoglobin (OHb), deoxyhemoglobin (RHb), and total hemoglobin (THb) concentrations along with temperature from the animal vaginal wall. As a control, saline was administered to both isoflurane- and ketamine-anesthetized animals, and did not show any significant changes in OHb, RHb, THb, or temperature. However, an administration of apomorphine (APO, 80 ㎍/kg) induced increases of OHb (63 ± 28 μM/DPF), RHb (35 ± 20 μM/DPF), and THb (98 ± 49 μM/DPF) in ketamine-anesthetized animals, while decreases of OHb (52 ± 76 μM/DPF) and THb (38 ± 30 μM/DPF) and an increase of RHb (28 ± 51 μM/DPF) were found in isoflurane-anesthetized animals. The vaginal temperature decreased from the baseline in both ketamine-(0.42℃) and isoflurane-(1.22℃)anesthetized animals. These results confirmed our hypothesis, and suggest that a preclinical study monitoring hemodynamic responses under anesthesia should employ an appropriate anesthetic agent for the study.

Correlation of Microvessel Density with Nuclear Pleomorphism, Mitotic Count and Vascular Invasion in Breast and Prostate Cancers at Preclinical and Clinical Levels

  • Muhammadnejad, Samad;Muhammadnejad, Ahad;Haddadi, Mahnaz;Oghabian, Mohammad-Ali;Mohagheghi, Mohammad-Ali;Tirgari, Farrokh;Sadeghi-Fazel, Fariba;Amanpour, Saeid
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.63-68
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    • 2013
  • Background: Tumor angiogenesis correlates with recurrence and appears to be a prognostic factor for both breast and prostate cancers. In the present study, we aimed to investigate the correlation of microvessel density (MVD), a measure of angiogenesis, with nuclear pleomorphism, mitotic count, and vascular invasion in breast and prostate cancers at preclinical and clinical levels. Methods: Samples from xenograft tumors of luminal B breast cancer and prostate adenocarcinoma, established by BT-474 and PC-3 cell lines, respectively, and commensurate human paraffin-embedded blocks were obtained. To determine MVD, specimens were immunostained for CD-34. Nuclear pleomorphism, mitotic count, and vascular invasion were determined using hematoxylin and eosin (H&E)-stained slides. Results: MVD showed significant correlations with nuclear pleomorphism (r=0.68, P=0.03) and vascular invasion (r=0.77, P=0.009) in breast cancer. In prostate cancer, MVD was significantly correlated with nuclear pleomorphism (r=0.75, P=0.013) and mitotic count (r=0.75, P=0.012). In the breast cancer xenograft model, a significant correlation was observed between MVD and vascular invasion (r=0.87, P=0.011). In the prostate cancer xenograft model, MVD was significantly correlated with all three parameters (nuclear pleomorphism, r=0.95, P=0.001; mitotic count, r=0.91, P=0.001; and vascular invasion, r=0.79, P=0.017; respectively). Conclusions: Our results demonstrate that MVD is correlated with nuclear pleomorphism, mitotic count, and vascular invasion at both preclinical and clinical levels. This study therefore supports the predictive value of MVD in breast and prostate cancers.

The Essential Prescriptions of the Golden Chamber (金匮要略) use of Shen Qi Pill(肾气丸)'s for qi's transformation(气化), truly embodies the analysis found in the Yellow Emperor internal classic(黃帝内经) describing the kidney functions (종"황제내경"신지공능탐석"금궤요략"신기환기화작용적체현(从"黃帝内经"肾之功能探析"金匮要略"肾气丸气化作用的体现))

  • Park, Eun Hee;Xie, Jing;Jia, Chunhua
    • Journal of Korean Medical classics
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    • v.26 no.1
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    • pp.39-45
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    • 2013
  • Objective : This article is based on a formula taken from Essential Prescriptions of the Golden Chamber(金匮要略). Shen Qi Pill(肾气丸) is generally used for such deficiency cases as: consumptive diseases, xiaoke(消渴) (waisting, thirst), beriberi, urinary problems during pregnancy, phlegm and so forth, and its main purpose is to treat Kidney Qi depletion, Qi transformation disorders, without obvious hot/cold appearance patterns. Method : Mainly through the literature study of related treatise on IInner Canon of the Yellow Emperor's internal classic(黃帝内经) and The Essential Prescriptions of the Golden Chamber. Result : According to the Yellow Emperor's internal classic, the Kidney has three main functions, storing essence, controlling the waters and holding Qi. Shen Qi Pill's(肾气丸) source formula is intended to supplement even though its constituent herbs aren't the warming type. To reinforce the Qi's transformation ability is considered to be a main function of the kidney organ, and in clinic, diagnosed kidney related problems and its treatment process are mainly associated with warming to help the Qi transforming. Conclusion : Thus recovering the kidneys Qi's transformation function is part of the process to eliminate diseases. Just cause the Kidney is deficient we shouldn't think immediately of using warming supplement herbs.

Neuroanatomical Localization of Rapid Eye Movement Sleep Behavior Disorder in Human Brain Using Lesion Network Mapping

  • Taoyang Yuan;Zhentao Zuo;Jianguo Xu
    • Korean Journal of Radiology
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    • v.24 no.3
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    • pp.247-258
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    • 2023
  • Objective: To localize the neuroanatomical substrate of rapid eye movement sleep behavior disorder (RBD) and to investigate the neuroanatomical locational relationship between RBD and α-synucleinopathy neurodegenerative diseases. Materials and Methods: Using a systematic PubMed search, we identified 19 patients with lesions in different brain regions that caused RBD. First, lesion network mapping was applied to confirm whether the lesion locations causing RBD corresponded to a common brain network. Second, the literature-based RBD lesion network map was validated using neuroimaging findings and locations of brain pathologies at post-mortem in patients with idiopathic RBD (iRBD) who were identified by independent systematic literature search using PubMed. Finally, we assessed the locational relationship between the sites of pathological alterations at the preclinical stage in α-synucleinopathy neurodegenerative diseases and the brain network for RBD. Results: The lesion network mapping showed lesions causing RBD to be localized to a common brain network defined by connectivity to the pons (including the locus coeruleus, dorsal raphe nucleus, central superior nucleus, and ventrolateral periaqueductal gray), regardless of the lesion location. The positive regions in the pons were replicated by the neuroimaging findings in an independent group of patients with iRBD and it coincided with the reported pathological alterations at post-mortem in patients with iRBD. Furthermore, all brain pathological sites at preclinical stages (Braak stages 1-2) in Parkinson's disease (PD) and at brainstem Lewy body disease in dementia with Lewy bodies (DLB) were involved in the brain network identified for RBD. Conclusion: The brain network defined by connectivity to positive pons regions might be the regulatory network loop inducing RBD in humans. In addition, our results suggested that the underlying cause of high phenoconversion rate from iRBD to neurodegenerative α-synucleinopathy might be pathological changes in the preclinical stage of α-synucleinopathy located at the regulatory network loop of RBD.