• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.191-199
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• 2000

Genomics is providing targets faster than we can validate them and combinatorial chemistry is providing new chemical entities faster than we can screen them. Historically, the drug discovery cascade has been established as a sequential process initiated with a potency screening against a selected biological target. In this sequential process, pharmacokinetics was often regarded as a low-throughput activity. Typically, limited pharmacokinetics studies would be conducted prior to acceptance of a compound for safety evaluation and, as a result, compounds often failed to reach a clinical testing due to unfavorable pharmacokinetic characteristics. A new paradigm in drug discovery has emerged in which the entire sample collection is rapidly screened using robotized high-throughput assays at the outset of the program. Higher-throughput pharmacokinetics (HTPK) is being achieved through introduction of new techniques, including automation for sample preparation and new experimental approaches. A number of in vitro and in vivo methods are being developed for the HTPK. In vitro studies, in which many cell lines are used to screen absorption and metabolism, are generally faster than in vivo screening, and, in this sense, in vitro screening is often considered as a real HTPK. Despite the elegance of the in vitro models, however, in vivo screenings are always essential for the final confirmation. Among these in vivo methods, cassette dosing technique, is believed the methods that is applicable in the screening of pharmacokinetics of many compounds at a time. The widespread use of liquid chromatography (LC) interfaced to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) allowed the feasibility of the cassette dosing technique. Another approach to increase the throughput of in vivo screening of pharmacokinetics is to reduce the number of sample analysis. Two common approaches are used for this purpose. First, samples from identical study designs but that contain different drug candidate can be pooled to produce single set of samples, thus, reducing sample to be analyzed. Second, for a single test compound, serial plasma samples can be pooled to produce a single composite sample for analysis. In this review, we validated the issue whether the second method can be applied to practical screening of in vivo pharmacokinetics using data from seven of our previous bioequivalence studies. For a given drug, equally spaced serial plasma samples were pooled to achieve a 'Pooled Concentration' for the drug. An area under the plasma drug concentration-time curve (AUC) was then calculated theoretically using the pooled concentration and the predicted AUC value was statistically compared with the traditionally calculated AUC value. The comparison revealed that the sample pooling method generated reasonably accurate AUC values when compared with those obtained by the traditional approach. It is especially noteworthy that the accuracy was obtained by the analysis of only one sample instead of analyses of a number of samples that necessitates a significant man-power and time. Thus, we propose the sample pooling method as an alternative to in vivo pharmacokinetic approach in the selection potential lead(s) from combinatorial libraries.

• Journal of the Korean Society of Visualization
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• v.9 no.4
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• pp.69-73
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• 2011

Butterflies have been known to suck viscous liquids through a long, cylindrical proboscis using the large pressure difference formulated by the cyclic expansion and contraction of a muscular pump located inside their head. However, there are few studies on the liquid-feeding phenomena in a live butterfly, because it is hard to observe the internal morphological structures under in vivo condition. In this study, the dynamic motion of the pump system in a butterfly was in vivo visualized using synchrotron X-ray micro-imaging technique to analyze the liquid-feeding mechanism. The period of the liquid-feeding process is about 0.3sec. The expansion stage is about two times larger than the contraction stage in one cycle. The cyclic variation of pump volume generate large negative suction pressure and the pressure difference inside the long proboscis of a butterfly is estimated to be larger than 1atm.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.420-432
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• 2021

Background: Many ginsenosides have been shown to be efficacious for major depressive disorder (MDD), which is a highly recurrent disorder, through several preclinical studies. We aimed to review the literature assessing the antidepressant effects of ginsenosides on MDD animal models, to establish systematic scientific evidence in a rigorous manner. Methods: We performed a systematic review on the antidepressant effects of ginsenoside evaluated in in vivo studies. We searched for preclinical trials from inception to July 2019 in electronic databases such as Pubmed and Embase. In vivo studies examining the effect of a single ginsenoside on animal models of primary depression were included. Items of each study were evaluated by two independent reviewers. A meta-analysis was conducted to assess behavioral changes induced by ginsenoside Rg1, which was the most studied ginsenoside. Data were pooled using the random-effects models. Results: A total of 517 studies were identified, and 23 studies were included in the final analysis. They reported on many ginsenosides with different antidepressant effects and biological mechanisms of action. Of the 12 included articles assessing ginsenoside Rg1, pooled results of forced swimming test from 9 articles (mean difference (MD): 20.50, 95% CI: 16.13-24.87), and sucrose preference test from 11 articles (MD: 28.29, 95% CI: 22.90-33.69) showed significant differences compared with vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity across studies. Conclusion: These estimates suggest that ginsenosides, including ginsenoside Rg1, reduces symptoms of depression, modulates underlying mechanisms, and can be a promising antidepressant.

• The Journal of Internal Korean Medicine
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• v.41 no.6
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• pp.993-1014
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• 2020

Objective: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Antioxidant stress and inflammatory reactions are important causes of neurodegenerative diseases and are major causes of PD. Many animal experiments have been aimed at treating PD using the antioxidant effects of various traditional medicines and dietary supplements. This review reports the research investigating the antioxidant effects of herbs in in vivo PD models. Methods: The study consisted of a database search for articles related to PD and herbal treatments using the OASIS, NDSL, KTKP, Korean KISS, PubMed, Science Direct, CNKI, Wanfang, and J-STAGE databases. The search period was limited from the start of the search engine application to November 14, 2019. Studies were selected to confirm the antioxidant effects of herbal medicines in an in vivo PD model. Results: Eighty-two studies were summarized for plant species, extracts (or compounds), animal models, neurotoxins, and functional results. The most frequently used herbal materials were Bacopa monnieri, Camellia sinensis, Centella asiatica, and Withania somnifera. MPTP and 6-OHDA were the most commonly used neurotoxins for inducing PD. Most studies confirmed an increased expression and activation of antioxidant enzymes and a decrease in oxidative stress. Herbal materials showed their antioxidant effects regardless of the order of treatment and confirmed their possible use as treatments for the prevention and treatment of neurodegeneration. Conclusion: Many herbal medicines have antioxidant effects and are likely to be effective in delaying neurodegenerative damage by inhibiting or reducing oxidative stress by expression of antioxidant enzymes.

• IMMUNE NETWORK
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• v.11 no.1
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• pp.1-10
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• 2011

Interleukin-7 (IL-7) is an essential cytokine for T cells. However, IL-7 is not produced by T cells themselves such that T cells are dependent on extrinsic IL-7. In fact, in the absence of IL-7, T cell development in the thymus as well as survival of naive T cells in the periphery is severely impaired. Furthermore, modulating IL-7 availability in vivo either by genetic means or other experimental approaches determines the size, composition and function of the T cell pool. Consequently, understanding IL-7 expression is critical for understanding T cell immunity. Until most recently, however, the spatiotemporal expression of in vivo IL-7 has remained obscured. Shortage of such information was partly due to scarce expression of IL-7 itself but mainly due to the lack of adequate reagents to monitor IL-7 expression in vivo. This situation dramatically changed with a recent rush of four independent studies that describe the generation and characterization of IL-7 reporter mice, all utilizing bacterial artificial chromosome transgene technology. The emerging consensus of these studies confirmed thymic stromal cells as the major producers of IL-7 but also identified IL-7 reporter activities in various peripheral tissues including skin, intestine and lymph nodes. Strikingly, developmental and environmental cues actively modulated IL-7 reporter activities in vivo suggesting that IL-7 regulation might be a new mechanism of shaping T cell development and homeostasis. Collectively, the availability of these new tools opens up new venues to assess unanswered questions in IL-7 biology in T cells and beyond.

• Proceedings of the Korean Society of Toxicology Conference
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• 2006.11a
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• pp.80-86
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• 2006

Bioequivalence is a term in pharmacokinetics used to access the expected in vivo biological equivalence of two proprietary preparations of a drug. Bioequivalence studies are usually performed for generic drugs. Two pharmaceutical products are bioequivalent if they are pharmaceutically equivalent and their bioavailabilioes after administration in the same molar dose are similar. Bioequivalence is usually accessed by single dose in vivo studies in healthy volunteers and the reference product is usually the innovator product that is marketed. Regulatory definition of bioequivalence is based on the statistical analysis of thebioavailability of the reference and test product. In general, two products are evaluated as bioequivalent if the 90% confidence interval of the relative mean Cmaxand AUC of the test to reference product are within 80.00% to 125.00% in the fasting state. Key process in bioequivalence study is development and validation of bioanalytical method, determination of the drug concentration in the biosamples (usually plasma or serum) obtained from volunteers, calculation of the pharmacokinetic parameters and statistical analysis of the pharmacokinetic parameters. Although current guidelines and regulations do not require the bioequivalence studies to be done under good laboratory practice (CLP), the issues to perform the bioequivalence studies under GLP environment is emerged both from the regulatory and industry side. GLP perspectives of bioequivalence studiesare needed to be discussed in respect to achieve quality assurance in bioequivalence studies.

• Journal of Food Hygiene and Safety
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• v.39 no.1
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• pp.35-43
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• 2024

Numerous methods have been applied to assess the antibacterial effectiveness of hand hygiene products. However, the different results obtained through various evaluation methods have complicated our understanding of the real efficacy of the products. Few studies have compared test methods for assessing the efficacy of hand hygiene products. In particular, reports on ex vivo pig skin testing are limited. This study aimed to compare and characterize the methodologies applied for evaluating hand hygiene products, involving in vitro, ex vivo, and in vivo approaches, applicable to both leave-on sanitizers and wash-off products. Our further aim was to enhance the reliability of ex vivo test protocols by identifying influential factors. We performed an in vitro method (EN1276) and an in vivo test (EN1499 and ASTM2755) with at least 20 participants, against Serratia marcescens or Escherichia coli and Staphylococcus aureus. For the ex vivo experiment, we used pig skin squares prepared in the same way as those used in the in vivo test method and determined the optimal treated sample volumes for sanitizers and the amount of water required to wash off the product. The hand sanitizers showed at least a 5-log reduction in bacterial load in the in vitro test, while they showed little antibacterial activity in the in vivo and ex vivo tests, particularly those with a low alcohol content. For the hand wash products, the in vitro test was limited because of bubble formation or the high viscosity of the products and it showed low antibacterial activity of less than a 1-log reduction against E. coli. In contrast, significantly higher log reductions were observed in ex vivo and in vivo tests, consistently demonstrating these results across the two methods. Our findings revealed that the ex vivo and in vivo tests reflect the two different antibacterial mechanisms of leave-on and wash-off products. Our proposed optimized ex vivo test was more rapid and more precise than the in vitro test to evaluate antibacterial results.

• International Journal of Industrial Entomology and Biomaterials
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• v.18 no.1
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• pp.49-52
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• 2009

An in vitro and in vivo studies were conducted to evaluate the antibacterial efficacy of certain botanicals viz., rhizomes of turmeric (Curcuma longa) and leaves of amla (Phyllanthus emblica), asparagus (Asparagus racemosus), bael (Aegle marmelos), boerhavia (Boerhavia diffusa), garlic (Allium sativum) and basil (Oscimum basicilum) against bacterial pathogens viz., Staphylococcus sp., Bacillus sp. and Klebsiella cloacae, of silkworm, Bombyx mori. Asparagus and basil, amla and boerhavia, basil and bael at concentration of 20, 000 ppm showed higher antibacterial activity against Staphylococcus sp., Bacillus sp., K. cloacae respectively, both in vitro and in vivo studies.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.44-53
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• 1999

The resistant strains due to the extended-spectrum $\beta$-lactamase (ESBL) were susceptible to cefatrizine combined with clavulanic acid. The purpose of this study was to evaluate the in vitro and in vivo antibacterial activities of cefatrizine/clavulanic acid (CTRZ/CV) combination at a ratio of 2 : 1 in comparison with cefaclor (CCLO), cefuroxime (CRXM), cefuroxime axetil (CRXMA) and amoxicillin/clavulanic acid (AMXCCV). CTRZ/CV showed good activity against laboratory strains of gram-positive and gram-negative bacteria and exhibited excellent antibacterial activity against $\beta$-lactamase-producing strains. The bactericidal activity of CTRZ/CV was superior to that of CCLO and CRXM, and almost equal to that of AMXCCV against the $\beta$-lactamase-producing strains. The in vitro results were substantiated. by in vivo mouse experimental infection studies with $\beta$-lactamase-producing and non-producing strains. In mixed experimental infection due to $\beta$-lactamase-producing and non-producing strains, the therapeutic efficacy of CTRZ/CV was superior to that of CTRZ, CCLO, CRXMA and AMXCCV. In respiratory tract infection in mice due to Klebsiella pneumoniae EB4O, CTRZ/CV was more erective than CCLO, CRXMA and AMXCCV and also more efficacious than CCLO, CRXMA and AMXCCV in urinary tract infection in mice due to Escherichia coli EB13. These results indicate that CTRZ/CV is a useful drug for the treatment of infection caused by $\beta$-1actamase-producing strains including ESBL-producing strains.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4853-4856
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• 2016

Objective: Gimatecan is a new camptothecin (CPT) analogue that inhibits tumor growth by targeting DNA topoisomerase I (TOP I) and introducing strong and persistent DNA cleavage. Anti-tumor activity has been demonstrated with a wide range of solid tumors in previous preclinical and clinical studies. Here, we investigated for the first time the effects of gimatecan on the proliferation of hepatocellular carcinoma (HCC) cells both in vitro and in vivo. Methods: Anticancer efficacy of gimatecan were evaluated in a panel of HCC cell lines and corresponding mouse xenograft models. Inhibition of cell proliferation was measured by CellTiter-Glo cell viability assay. In vivo, gimatecan and control preparations were orally administered every four days, for a total of four times. Tumor volume and body weights of the mice were measured twice weekly. Results: In vitro cytotoxicity evaluation showed that gimatecan inhibited the proliferation of a large panel of HCC cell lines in a dose dependent manner, with IC50 values ranging between 12.1~1085.0 nM. In vivo evaluation in mouse xenograft models showed significant antitumor effects of gimatecan at 0.8mg/kg and 0.4mg/kg as compared to the control group. Conclusion: This study suggested that gimatecan may have the potential to be used as a chemotherapeutic agent for the treatment of HCC.