• Title/Summary/Keyword: In vivo development

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Antifungal Activities of Crude Extractum from Camellia semiserrata Chi (Nanshancha) Seed Cake Against Colletotrichum musae, Colletotrichum gloeosporioides and Penicillium italicum in vitro and in vivo Fruit Test

  • Meng, Xiangchun;Li, Jun;Bi, Fangcheng;Zhu, Lixue;Ma, Zhiyu
    • The Plant Pathology Journal
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    • v.31 no.4
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    • pp.414-420
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    • 2015
  • Antifungal activities of crude extractum of Nanshancha Seed Cake (NSC), to inactivate postharvest pathogens were investigated. Highest inhibitory rate was found against C. musae, C. gloeosporioides and C. papaya P.Henn, which was much stronger than that by tea saponin. Compared to tea saponin, effects of NSC extractum was relatively weak and similar on C. gloeosporioides Penzig and P. italicum. In an in vivo study, best controlling effects by NSC extractum was found with banana anthracnose disease development, which showed no inhibitory effects by tea saponin. NSC extractum controlled in vitro C. musae growth through directly inhibiting germination rate and germ tube elongation, and causing distortation, rupture and indentation of C. musae mycelium. In banana fruit subject to C. musae inoculation, higher PAL, POD, GLU and CHT activity was observed in banana fruit treated with crude NSC extractum than that of water control fruits. Current study proved the best controlling effects of crude NSC extractum in C. musae in vitro and in vivo development, which through direct inhibition of C. musae growth and increasing defense system of the banana fruit.

Development of SD-OCT for Imaging the in vivo Human Tympanic Membrane

  • Cho, Nam-Hyun;Jung, Un-Sang;Kwon, Hyeong-Il;Jeong, Hyo-Sang;Kim, Jee-Hyun
    • Journal of the Optical Society of Korea
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    • v.15 no.1
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    • pp.74-77
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    • 2011
  • We report a novel extension of 840 nm wavelength- based spectral domain optical tomography to in vivo/real-time human middle ear diagnosis. The system was designed to access the middle ear region with a specifically dedicated handheld probe. The real-time displaying feature was mandatory for in vivo imaging human subject with the handheld probe, and the system could provide about 20 frames per second for 2048 pixels by 1000 A-scans without using any graphics process units under the Labview platform. The inner ear structure of a healthy male volunteer was imaged with the developed system with the axial and lateral resolutions of $15\;{\mu}m$ and $30\;{\mu}m$, respectively. The application of the OCT technology to early diagnose otitis media(OM) is very promising and could be another extensive branch in the OCT field because it provides the depth resolved image including tympanic membrane (TM) and structures below TM whereas the conventional otoscope technique only gives asurface image of the TM.

Potency and plasma protein binding of drugs in vitro-a potentially misleading pair for predicting in vivo efficacious concentrations in humans

  • Yim, Dong-Seok
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.4
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    • pp.231-236
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    • 2019
  • In drug discovery or preclinical stages of development, potency parameters such as $IC_{50}$, $K_i$, or $K_d$ in vitro have been routinely used to predict the parameters of efficacious exposure (AUC, $C_{min}$, etc.) in humans. However, to our knowledge, the fundamental assumption that the potency in vitro is correlated with the efficacious concentration in vivo in humans has not been investigated extensively. Thus, the present review examined this assumption by comparing a wide range of published pharmacokinetic (PK) and potency data. If the drug potency in vitro and its in vivo effectiveness in humans are well correlated, the steady-state average unbound concentrations in humans [$C_{u_-ss.avg}=f_u{\cdot}F{\cdot}Dose/(CL{\cdot}{\tau})=f_u{\cdot}AUCss/{\tau}$] after treatment with approved dosage regimens should be higher than, or at least comparable to, the potency parameters assessed in vitro. We reviewed the ratios of $C_{u_-ss.avg}$/potency in vitro for a total of 54 drug entities (13 major therapeutic classes) using the dosage, PK, and in vitro potency reported in the published literature. For 54 drugs, the $C_{u_-ss.avg}$/in vitro potency ratios were < 1 for 38 (69%) and < 0.1 for 22 (34%) drugs. When the ratios were plotted against $f_u$ (unbound fraction), "ratio < 1" was predominant for drugs with high protein binding (90% of drugs with $f_u{\leq}5%$; i.e., 28 of 31 drugs). Thus, predicting the in vivo efficacious unbound concentrations in humans using only in vitro potency data and $f_u$ should be avoided, especially for molecules with high protein binding.

Effect of Osmolarity of Culture Medium on Imprinting and Apoptotic Gene Expression in Miniature Pig Nuclear Transfer Embryos

  • Park, Mi-Rung;Hwang, In-Sun;Shim, Joo-Hyun;Moon, Hyo-Jin;Kim, Dong-Hoon;Ko, Yeoung-Kyu;Seong, Hwan-Hoo;Im, Gi-Sun
    • Reproductive and Developmental Biology
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    • v.32 no.3
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    • pp.183-191
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    • 2008
  • This study was conducted to investigate the development and gene expression in miniature pig nuclear transfer (mNT) embryos produced under different osmolarity culture conditions. Control group of mNT embryos was cultured in PZM-3 for 6 days. Treatment group of mNT embryos was cultured in modified PZM-3 with NaCl (mPZM-3, 320 mOsmol) for 2 days, and then cultured in PZM-3 (270 mOsmol) for 4 days. Blastocyst formation rate of the treatment group was significantly higher than the control and the apoptosis rate was significantly lower in treatment group. Bax-$\alpha$ and caspase-3 mRNA expression were significantly higher in the control than the treatment group. Also, the majority of imprinting genes were expressed aberrantly in in vitro produced mNT blastocysts compared to in vivo derived blastocyst H19 and Xist mRNA expression were significantly lower in the control than the treatment group or in vivo. IGF2 mRNA expression was significantly higher in the control than the treatment group or in vivo. IGF2r mRNA expression was significantly lower in the control. Methylation profiles of individual DNA strands in H19 upstream T-DMR sequences showed a similar methylation status between treatment group and in vivo. These results indicate that the modification of osmolarity in culture medium at early culture stage could provide more beneficial culture environments for mNT embryos.

Effect of Arsenic on Acetylcholine-Induced Relaxation in Blood Vessels in vitro cad in vivo

  • Lee, M.Y.;Chung, S.M.;Bae, O.N.;Chung, J.H.
    • Proceedings of the Korean Society of Food Hygiene and Safety Conference
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    • 2002.05a
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    • pp.137-137
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    • 2002
  • Several epidemiologidal studies suggested that arsenic exposure was strongly correlated with the development of cardiovascular disease such as hypertension. In order to examine whether arsenic affects vasomotor tone in blood vessels, we investigated the effect of arsenic on agonist-induced vasorelaxation using the isolated rat aortic ring in in vitro organ bath system. Treatment with arsenite inhibited acetylcholine-induced relaxation of aortic rings in a concentration- dependent manner. The inhibitory effects by arsenic were also observed in the relaxation induced by sodium nitroprusside, a NO-donor. Consistent with these findings, the cGMP levels stimulated by acetylcholine in blood vessels were reduced significantly by arsenite treatment. In addition, higher concentration of arsenite decreased the relaxation by 8-Br-cGMP, a cGMP analog, in aortic rings without endothelium. These in vitro results indicated that arsenite that arsenite was capable of suppressing acetylcholine-induced relaxation in blood vessels by inhibiting production of nitric oxide in endothelial cells and by impairing the relaxation machinary in smooth muscle cells. In vivo studies revealed that the reduction of blood pressure by acetylcholine infusion was signigicantly suppressed after arsenite was administered intravenously to rate. These data suggest that vasomotor tone impaired by arsenite exposure may be one of the contrbuting factors in development of cardiovascular disease.

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Saturable Disposition of Taurine in the Cerebrospinal Fluid of the Rat

  • Chung, Suk-Jae
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.11a
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    • pp.99-113
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    • 1996
  • Taurine, a ${\beta}$-amino acid, plays an important role as a neuromodulator and is necessary for the normal development of the brain. Since de novo synthesis of taurine in the brain is minimal and in vivo studies suggest that taurine does not cross the blood-brain barrier, the blood-cerebrospinal fluid (CSF) barrier is likely to play a role in taurine transport between the central nervous system and the systemic circulation. Therefore, we examined in vivo elimination of taurine from the CSF in the rat to characterize in vivo kinetics of elimination for taurine from the CSF is consistent with the in vitro study. Using a stereotaxic device, cannulaes were placed into the lateral ventricle and the cisterna magna of the rat. Radio-labelled taurine and inulin (a marker of CSF flow) were injected into the lateral ventricle, and the concentrations of the labelled compounds in the CSF were monitored for up to 3 hrs in the cisterna magna. The apparent clearance of taurine from CSF was greater than the estimated CSF flow (p<0.005), indicating that there is a clearance process in addition to the CSF flow. Taurine distribution into the choroid plexus was at least 10 fold higher than that found in other brain areas (e.g., cerebellum, olfactory bulb and cortex). When unlabelled taurine was co-administered with radio-labelled taurine, the apparent clearance of the labeled taurine was reduced (p<0.01), suggesting a saturable disposition of taurine from CSF. Distribution of taurine into the choroid plexus, cerebellum, olfactory bulb and cortex was similarly diminished, indicating that the saturable uptake of taurine into these tissues is responsible for the non-linear disposition. A pharmacokinetic model involving first order elimination and saturable distribution described these data adequately. The Michaelis-Menten rate constant estimated from in vivo elimination study is similar to that obtained in the in vitro uptake experiment Collectively, our results demonstrate that taurine is transported in the choroid plexus via a taurine is cleared from the CSF via a saturable process. This process may be functionally relevant to taurine homeostasis in the brain.

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Ectopic Expression of Cenexin1 S796A Mutant in $ODF2^{+/-}$ Knockout Background Causes a Sperm Tail Development Defect

  • Lee, Kyung Ho
    • Development and Reproduction
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    • v.16 no.4
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    • pp.363-370
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    • 2012
  • The outer dense fiber 2 (ODF2) protein is an important component of sperm tail outer dense fiber and localizes at the centrosome. It has been reported that the RO072 ES cell derived homozygote knock out of ODF2 results in an embryonic lethal phenotype, and XL169 ES cell derived heterozygote knock out causes severe defects in sperm tail development. The ODF2s splicing variant, Cenexin1, possesses a C-terminal extension, and the phosphorylation of serine 796 residue in an extended C-terminal is responsible for Plk1 binding. Cenexin1 assembles ninein and causes ciliogenesis in early stages of the cell cycle in a Plk1-independent manner. Alternatively, in the late stages of the cell cycle, G2/M phase, Cenexin1 binds to Plk1 and results in proper mitotic progression. In this study, to identify the in vivo function of Plk1 binding to phosphorylated Cenexin1 S796 residue, and to understand the in vivo functional differences between ODF2 and Cenexin1, we generated ODF2/Cenexin1 S796A/Cenexin1 WT expressing transgenic mice in a RO072 ES cell derived $ODF2^{+/-}$ knock out background. We observed a severe defect of sperm tail development by ectopic expression of Cenexin1 S796A mutant and no phenotypic differences between the ectopic expression of ODF2/Cenexin1 WT in $ODF2^{+/-}$ background and in normal wild type mice.

In Vivo Antifungal Activities of 67 Plant Fruit Extracts Against Six Plant Pathogenic Fungi

  • Choi Gyung-Ja;Kim Jin-Cheol;Jang Kyoung-Soo;Lim He-Kyoung;Park Il-Kwon;Shin Sang-Chul;Cho Kwang-Yun
    • Journal of Microbiology and Biotechnology
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    • v.16 no.3
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    • pp.491-495
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    • 2006
  • Methanol extracts of fruits of 67 plants were screened for in vivo antifungal activity against Magnaporthe grisea, Corticium sasaki, Botrytis cinerea, Phytophthora infestans, Puccinia recondita, and Blumeria graminis f. sp. hordei. Among them, 13 plant extracts ($3,000\;{\mu}g/ml$) showed more than 90% disease-control efficacy against at least one of six plant diseases. Specifically, the extracts of Aleurites fordii, Angelica dahurica, Camellia japonica, Chamaecyparis pisifera, Pittosporum tobira, and Styrax japonica controlled more than 90% of the development of rice blast at $1,000{\mu}g/ml$. Extracts of both S. japonica and A. dahurica fruits at $333{\mu}g/ml$ concentration displayed strong antifungal activity against M. grisea on rice seedlings.

Overexpression of RUNX3 Inhibits Malignant Behaviour of Eca109 Cells in Vitro and Vivo

  • Chen, Hua-Xia;Wang, Shuai;Wang, Zhou;Zhang, Zhi-Ping;Shi, Shan-Shan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1531-1537
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    • 2014
  • Runt-related transcription factor 3 (RUNX3) is a tumor suppressor gene whose reduced expression may play an important role in the development and progression of esophageal squamous cell cancer (ESCC). The aim of this study was to investigate the clinical relevance of RUNX3 in ESCC patients and effects of overexpression on biological behaviour of Eca109 cells in vitro and in vivo. Immunohistochemistry was performed to detect the clinical relevance of RUNX3 and lymph node metastasis in 80 ESCC tissues and 40 non-cancerous tissues using the SP method. RT-PCR and Western blotting were applied to assess the RUNX3 level and verify the Eca109 cell line with stable overexpression. Localization of RUNX3 proteins was performed by cell immunofluorescence. CCK-8 and Scrape motility assays were used to determine proliferation and migration and the TUNEL assay to analyze cell apoptosis. Invasive potential was assessed in cell transwell invasion experiments. In nude mice, tumorigenesis in vivo was determined. Results showed decreased expression of RUNX3 in esophageal tissue to be significantly related to lymph node metastasis (LNM) (P<0.01). In addition, construction of a recombinant lentiviral vector and transfection into the human ESCC cell line Eca109 demonstrated that overexpression could inhibit cell proliferation, migration and invasion, and induce apoptosis. The in vivo experiments in mice showed tumorigenicity and invasiveness to be significantly reduced. Taken together, our studies indicate that underexpression of RUNX3 in human ESCC tissue is significantly correlated with progression. Restoration of RUNX3 expression significantly inhibits ESCC cells proliferation, migration, invasion and tumorigenesis.