• Title/Summary/Keyword: Safety pharmacology

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Mutagenic Assessment of Olmesartan Cilexetil by Bacterial Mutation Assay

  • Kim, Ji Won;Ahn, Ilyoung;Ryu, Sung Ha;Jeon, Hong Ryeol;Lee, Bong Sang;Kim, Kyu-Bong
    • Toxicological Research
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    • v.29 no.3
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    • pp.217-219
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    • 2013
  • Hypertension is a serious health problem due to high frequency and concomitant other diseases including cardiovascular and renal dysfunction. Olmesartan cilexetil is a new antihypertensive drug associated with angiotensin II receptor antagonist. This study was conducted to evaluate the mutagenicity of olmesartan cilexetil by bacterial reverse mutation test using Salmonella typhimurium (TA100, TA1535, TA98, and TA1537) and Escherichia coli (WP2 uvrA). At the concentrations of 0, 62, 185, 556, 1667, and 5000 ${\mu}g$/plate, olmesartan cilexetil was negative in both Salmonella typhimurium and Escherichia coli regardless of presence or absence of metabolic activation system (S9 mix). These results demonstrate that olmesartan cilexetil does not induce bacterial reverse mutation.

Looking Inside the Cell for Mechanisms of Immunotoxicity: Experimental Design and Approaches Aimed Toward Elucidation of 2,3,7,8-Tetrachlor- dibenzo-p-dioxin-mediated B Cell Dysfunction

  • Norbert E. Kaminski;Kang, Jong-Soon
    • Toxicological Research
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    • v.17
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    • pp.205-210
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    • 2001
  • One of the major focuses and perhaps the greatest challenges during the past decade in the discipline of immunotoxicology has been the elucidation of the molecular mechanisms responsible for immunotoxicity by specific agents. Much is currently understood about the basic underlying intracellular processes that control leukocyte effector function. This fundamental information in cell biology can now be applied toward developing systematic approaches, through the application of cell and molecular biology techniques, to identify the intracellular targets and processes disrupted by immunotoxicants. The objective of this paper is two fold. First to discuss fundamental principles of experimental design aimed at elucidation of cellular mechanisms in immunotoxicology; and second to discuss the application of molecular biology techniques in characterizing the mechanism of TCDD-induced B cell dysfunction as a working example.

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Chirality of Drug Molecules and Biological Activity (의약품의 손대칭성과 생리 활성)

  • 권순경
    • Biomolecules & Therapeutics
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    • v.4 no.3
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    • pp.209-223
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    • 1996
  • Chirality is important in the context of biological activity because at a molecular level, asymmetry dominates biological process. While most pharmaceuticals of natural origin are single enantiomers, most of the synthesized chiral drugs are used in the form of racemic mixtures of two or more diastereomers. The enantiomers of a racemic drug generally differ in pharmacodynamic and pharmacokinetic properties as a consequence of stereoselective interaction with optically active molecular components of living organism. In pharmacokinetics and pharmacodynamics enantioselectivity plays an important role. The information on the sum of eutomer and distorter in a racemic drugs is very important in the estimation of therapeutic advantage and/or toxicity of racemates. The choice of preferentially developing a single enantiomer should be based on actual therapeutic advantages and especially improved safety.

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Isolation and Structure Determination of Coumarin Derivatives from the Roots of Angelica dahurica

  • Kim, Ji-Yeon;Son, Jong-Keun;Song, Dong-Keun
    • Journal of Evidence-Based Herbal Medicine
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    • v.3 no.1
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    • pp.35-41
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    • 2010
  • From the roots of Angelica dahurica Bentham et Hooker (Umbelliferae), three known coumarin derivatives have been isolated and identified as 8-(2-hydroxy-3-methoxy-3-methylbutyloxy) psoralen, 5,8-di(2,3-dihydroxy-3-methylbutyloxy) psoralen, 9-[3-($\beta$-D-glucopyranosyloxy)-2-hydroxy-3-methylbutoxy]-7H-furo[3,2-g][1]benzopyran-7-one. This is the first report of the occurrence of these compounds in this plant. These three compounds were tested for activity in septic shock model. Among these compounds, 2 showed relatively strong preventive activity against septic shock.

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Plant Cell Wall Polysaccharides as Potential Resources for the Development of Novel Prebiotics

  • Yoo, Hye-Dong;Kim, Do-Jung;Paek, Seung-Ho;Oh, Seung-Eun
    • Biomolecules & Therapeutics
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    • v.20 no.4
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    • pp.371-379
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    • 2012
  • Prebiotic oligosaccharides, with a degree of polymerization (DP) of mostly less than 10, exhibit diverse biological activities that contribute to human health. Currently available prebiotics are mostly derived from disaccharides and simple polysaccharides found in plants. Subtle differences in the structures of oligosaccharides can cause significant differences in their prebiotic properties. Therefore, alternative substances supplying polysaccharides that have more diverse and complex structures are necessary for the development of novel oligosaccharides that have actions not present in existing prebiotics. In this review, we show that structural polysaccharides found in plant cell walls, such as xylans and pectins, are particularly potential resources supplying broadly diverse polysaccharides to produce new prebiotics.

COVID-19 Vaccine: Critical Questions with Complicated Answers

  • Haidere, Mohammad Faisal;Ratan, Zubair Ahmed;Nowroz, Senjuti;Zaman, Sojib Bin;Jung, You-Jung;Hosseinzadeh, Hassan;Cho, Jae Youl
    • Biomolecules & Therapeutics
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    • v.29 no.1
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    • pp.1-10
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    • 2021
  • COVID-19 has caused extensive human casualties with significant economic impacts around the globe, and has imposed new challenges on health systems worldwide. Over the past decade, SARS, Ebola, and Zika also led to significant concerns among the scientific community. Interestingly, the SARS and Zika epidemics ended before vaccine development; however, the scholarly community and the pharmaceutical companies responded very quickly at that time. Similarly, when the genetic sequence of SARS-CoV-2 was revealed, global vaccine companies and scientists have stepped forward to develop a vaccine, triggering a race toward vaccine development that the whole world is relying on. Similarly, an effective and safe vaccine could play a pivotal role in eradicating COVID-19. However, few important questions regarding SARS-CoV-2 vaccine development are explored in this review.

Current Development Status of Cytokines for Cancer Immunotherapy

  • Kyoung Song
    • Biomolecules & Therapeutics
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    • v.32 no.1
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    • pp.13-24
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    • 2024
  • Cytokines influence the overall cancer immune cycle by triggering tumor antigen expression, antigen presenting, immune cell priming and activation, effector immune cell recruitment and infiltration to cancer, and cancer killing in the tumor microenvironment (TME). Therefore, cytokines have been considered potential anti-cancer immunotherapy, and cytokine-based anti-cancer therapies continue to be an active area of research and development in the field of cancer immunotherapy, with ongoing clinical trials exploring new strategies to improve efficacy and safety. In this review, we examine past and present clinical developments for major anticancer cytokines, including interleukins (IL-2, IL-15, IL-12, IL-21), interferons, TGF-beta, and GM-CSF. We identify the current status and changes in the technology platform being applied to cytokine-based immune anti-cancer therapeutics. Through this, we discuss the opportunities and challenges of cytokine-based immune anti-cancer treatments in the current immunotherapy market and suggest development directions to enhance the clinical use of cytokines as immuno-anticancer drugs in the future.

Multiple Alternating Immunizations with DNA Vaccine and Replication-incompetent Adenovirus Expressing gB of Pseudorabies Virus Protect Animals Against Lethal Virus Challenge

  • Kim, Seon-Ju;Kim, Hye-Kyung;Han, Young-Woo;Aleyas, Abi G.;George, Junu A.;Yoon, Hyun-A;Yoo, Dong-Jin;Kim, Koan-Hoi;Eo, Seong-Kug
    • Journal of Microbiology and Biotechnology
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    • v.18 no.7
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    • pp.1326-1334
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    • 2008
  • The prime-boost vaccination with DNA vaccine and recombinant viral vector has emerged as an effective prophylactic strategy to control infectious diseases. Here, we compared the protective immunities induced by multiple alternating immunizations with DNA vaccine (pCIgB) and replication-incompetent adenovirus (Ad-gB) expressing glycoprotein gB of pseudorabies virus (PrV). The platform of pCIgB-prime and Ad-gB-boost induced the most effective immune responses and provided protection against virulent PrV infection. However, priming with pCIgB prior to vaccinating animals by the DNA vaccine-prime and Ad-boost protocol provided neither effective immune responses nor protection against PrV. Similarly, boosting with Ad-gB following immunization with DNA vaccine-prime and Ad-boost showed no significant responses. Moreover, whereas the administration of Ad-gB for primary immunization induced Th2-type-biased immunity, priming with pCIgB induced Th1-type-biased immunity, as judged by the production of PrV-specific IgG isotypes and cytokine IFN-$\gamma$. These results indicate that the order and injection frequency of vaccine vehicles used for heterologous prime-boost vaccination affect the magnitude and nature of the immunity. Therefore, our demonstration implies that the prime-boost protocol should be carefully considered and selected to induce the desired immune responses.