• Title/Summary/Keyword: Cell delivery

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Genotoxicity of Aluminum Oxide ($Al_2O_3$) Nanoparticle in Mammalian Cell Lines

  • Kim, Youn-Jung;Choi, Han-Saem;Song, Mi-Kyung;Youk, Da-Young;Kim, Ji-Hee;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.5 no.2
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    • pp.172-178
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    • 2009
  • Nanoparticles are small-scale substances (<100 nm) with unique properties, complex exposure and health risk implications. Aluminum oxide ($Al_2O_3$) nanoparticles (NP) have been widely used as abrasives, wear-resistant coatings on propeller shafts of ships, to increase the specific impulse per weight of composite propellants used in solid rocket fuel and as drug delivery systems to increase solubility. However, recent studies have shown that nano-sized aluminum (10 nm in diameter) can generate adverse effects, such as pulmonary response. The cytotoxicity and genotoxicity of $Al_2O_3$ NP were investigated using the dye exclusion assay, the comet assay, and the mouse lymphoma thymidine kinase (tk$^{+/-}$) gene mutation assay (MLA). IC$_{20}$ values of $Al_2O_3$ NP in BEAS-2B cells were determined the concentration of 273.44 $\mu$g/mL and 390.63 $\mu$g/mL with and without S-9. However IC$_{20}$ values of $Al_2O_3$ NP were found nontoxic in L5178Y cells both of with and without S-9 fraction. In the comet assay, L5178Y cells and BEAS-2B cells were treated with $Al_2O_3$ NP which significantly increased 2-fold tail moment with and without S-9. Also, the mutant frequencies in the $Al_2O_3$ NP treated L5178Y cells were increased compared to the vehicle controls with S-9. The results of this study indicate that $Al_2O_3$ NP can cause primary DNA damage and cytotoxicity but not mutagenicity in cultured mammalian cells.

Synthesis and Properties of 5-Aminosalicyl-taurine as a Colon-specific Prodrug of 5-Aminosalicylic Acid

  • Jung, Yun-Jin;Kim, Hak-Hyun;Kong, Hye-Sik;Kim, Young-Mi
    • Archives of Pharmacal Research
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    • v.26 no.4
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    • pp.264-269
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    • 2003
  • 5-Aminosalicylic acid (5-ASA) is an active ingredient of therapeutic agents used for Crohn s disease and ulcerative colitis. Because it is absorbed rapidly and extensively in the upper intestine, delivery of the agent specifically to the colon is necessary. We selected taurine as a colon-specific promoiety and designed 5-aminosalicyltaurine (5-ASA-Tau) as a new colon-specific prodrug of 5-aminosalicylic acid (5-ASA). It was expected that introduction of taurine would restrict the absorption of the prodrug and show additive effect to the anti-inflammatory action of 5-ASA after hydrolysis. 5-ASA-Tau was prepared in good yield by a simple synthetic route. The apparent partition coefficient of 5-ASA-Tau in 1-octanol/pH 6.8 phosphate buffer or $CHCl_3$/pH 6.8 phosphate buffer was 0.10 or 0.18, respectively, at $37^{\circ}C$. To determine the chemical and biochemical stability in the upper intestinal environment, 5-ASA-Tau was incubated in pH 1.2 and 6.8 buffer solutions, and with the homogenates of tissue and contents of stomach or small intestine of rats at $37^{\circ}C$. 5-ASA was not detected from any of the incubation medium with no change in the concentration of 5-ASA-Tau. On incubation of 5-ASA-Tau with the cecal and colonic contents of rats, the fraction of the dose released as 5-ASA was 45% and 20%, respectively, in 8 h. Considering low partition coefficient and stability in the upper intestine, 5-ASA-Tau might be nonabsorbable and stable in the upper intestine. After oral administration, it would be delivered to the colon in intact form and release 5-ASA and taurine. These results suggested 5-ASA-Tau as a promising colon-specific prodrug of 5-ASA.

A Study on the Effect of Contribution to addressing to Customer Complaints of After-Sales Service Factors (애프터서비스품질 요인이 고객 불만족 해소에 미치는 영향에 관한 연구)

  • Lee, Jae-Joon;Cho, Jin-Hyung;Koo, Ja-Hwal
    • Journal of Korean Society of Industrial and Systems Engineering
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    • v.32 no.1
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    • pp.137-146
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    • 2009
  • Researches on after-sales quality have centered on home electric appliances, figuring out how factors influencing after-sales service quality are causally related to customer's behavioral intentions, via consumer satisfaction as an intermediary parameter In most cases of after-sales service in home electric appliances, upon customer's request, service agents make a visit to where the appliance is installed, and check the product and do repairs. However, in case of a small portable device such as a cell phone, which people carry around at all times, most of the times customers themselves show up at the after-sales center, and demand a check-up and repairs. The main difference here is that the after-sales services are provided when a product can no longer perform its basic function and customer dissatisfaction is already up. In this case, the basic function of a product corresponds to must-be factor according to Kano model. The goal of our research is to identify critical factors for effective and efficient after-sales service, and how to monitor them on a routine basis. In our research, the quality after-sales service consists of three dimensions, interactive quality, result quality, and physical environment quality. We set up variables for each dimension, which would measure from customer's perspective key determining factors in service delivery process. Instead of focusing on customer satisfaction aspect, we focused on how after-sales service factors contribute to addressing customer complaints. Additionally, our future research would aim to verify how customer's behavioral intentions are affected, as the resolution of consumer complaints becomes more successful when adjustment of relevant quality factors improves after-sales service quality.

A Simple, Reliable, and Inexpensive Intraoperative External Expansion System for Enhanced Autologous Structural Fat Grafting

  • Oranges, Carlo M.;Tremp, Mathias;Ling, Barbara;Wettstein, Reto;Largo, Rene D.;Schaefer, Dirk J.
    • Archives of Plastic Surgery
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    • v.43 no.5
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    • pp.466-469
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    • 2016
  • External volume expansion of the recipient site by suction has been proposed as a way of improving fat graft survival. The objective of this study was to present an innovative and simple intraoperative external expansion system to enhance small-volume autologous fat grafting (40-80 mL) and to discuss its background and its mechanism of action. In this system, expansion is performed using a complete vacuum delivery system known as the Kiwi VAC-6000M with a PalmPump (Clinical Innovations). The recipient site is rapidly expanded intraoperatively 10 times for 30 seconds each with a negative pressure of up to 550 mm Hg before autologous fat injection. During this repetitive stimulation, the tissues become grossly expanded, developing macroscopic swelling that regresses slowly over the course of hours following the cessation of the stimulus. The system sets various mechanisms in motion, including scar release, mechanical stimulation, edema, ischemia, and inflammation, which provide an environment conducive for cell proliferation and angiogenesis. In order to maintain the graft construct in its expansive state, all patients are encouraged postoperatively to use the Kiwi three times daily for one minute per session over the course of three days. The handling of this system is simple for both the patients and the surgeon. Satisfactory clinical outcomes have been achieved without significant complications.

Population-Based Cervical Screening Outcomes in Turkey over a Period of Approximately Nine and a Half Years with Emphasis on Results for Women Aged 30-34

  • Sengul, Demet;Altinay, Serdar;Oksuz, Hulya;Demirturk, Hanife;Korkmazer, Engin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2069-2074
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    • 2014
  • Purpose: To appraise the frequency of cervical cytological abnormalities in a population at normal risk via analysing the archive records of cytology for the period of approximately 9,5 years, comparing them with patient demographic charecteristics, and discuss the results for women under age of 35. Materials and Methods: A total of 32,578 cases of Pap smears were retrieved and analysed from our archive included the Pap tests performed between January 2001 and April 2010 at the Early Cancer Screening, Diagnosing and Education Center by the consent of three pathologists via utilizing the Bethesda System Criteria 2001 and the results were compared with some demographical characteristics. Results: Our rate of the cervical cytological abnormality was 1.83%, with ASCUS in 1.18%, LSIL in 0.39, HSIL in 0.16%, AGUS in 0.07%, squamous cell carcinoma in 0.02%, and adenoarcinoma in 0.006%. Cytological abnormalities were detected mostly in those with higher age, lower parity, and premenopausal period whereas the smoking status was without influence. Bacterial vaginosis (5.6%) was the most frequent infectious finding (Candida albicans 2.7%; Actinomyces sp. 1.3%; and Trichomonas vaginalis 0.2%) detected on the smears. The rate of abnormal cervical cytology was 9.5% among the women aged between 30-34. Conclusions: Early detection of the cervical abnormalities by means of the regular cervical cancer screening programmes is useful to attenuate the incidence, mortality, and morbidity of cervical cancer. Our prevalence of the cytological abnormalities was much lower than the one in Western populations in general but very similar to those reported from other Islamic countries that may be explained by the conservative lifestyle and the lower prevalence of HPV in Turkey. A remarkable rate of abnormal cervical cytology of women aged 30-34 was pointed out in the present study.

Immunohistochemical Characterization of the Human Sublingual Mucosa

  • Choi, Young-Nim;Hong, Sung-Doo;Lee, Jong-Ho;Cuburu, Nicolas;Saletti, Giulietta;Czerkinsky, Cecil
    • International Journal of Oral Biology
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    • v.34 no.3
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    • pp.131-135
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    • 2009
  • The sublingual locus has recently received great attention as a delivery site for various immunotherapies, including those that induce allergen-specific tolerance, and for vaccines that generate protective immunity. To further understand the immune functions of the human sublingual mucosa, we characterized the distribution of various immunocytes therein by immunohistochemistry. We identified professional antigen presenting cells (APCs), including Langerhans cells (LCs) and macrophages. $CD1a^+$ and $langerin^+$ LCs were further found to be distributed in the basal and supra-basal layers of the epithelium, and macrophages were identified in the lamina propria. HLA-$DR^+$ cells were observed in both the epithelium and the lamina propria, which mirrors the tissue distribution of LCs and macrophages within these tissues. $CD3^+$, $CD4^+$, and $CD8^+$ T cells were found to be distributed along the basal layer of the epithelium and also in the lamina propria. Although B cells, plasma cells, and $Foxp3^+$ regulatory T cells (Tregs) were only occasionally observed in the human sublingual mucosa in the absence of inflammation, they did show enrichment at inflammatory sites. Hence, we have further elucidated the immune cell component distribution in human sublingual mucosa.

Effect of Solvents and Surfactants on the Whole-cell Bioassay for Screening Quorum Sensing Autoinducers Using the Recombinant Agrobacterium tumefaciens NTL4 Strain (재조합 Agrobacterium tumefaciens NTL4 균주를 이용한 quorum Sensing Autoinducer 검색에 용매와 계면활성제가 미치는 영향)

  • Koh, Kyong-Pyo;Kim, Yeon-Hee;Kim, Jung Sun;Park, Sunghoon
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.4
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    • pp.260-267
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    • 2006
  • The Liquid Culture Assay using a recombinant Agrobacterium tumefaciens strain has been developed as a means for quorum sensing autoinducer screening. However, the low aqueous solubility of marine natural product extracts used as potential autoinducers has been a hindrance in the screening process. Although the addition of organic solvents and/or surfactants could increase aqueous solubility, errors in data interpretation including false positive results could be a serious problem. Therefore, determining the best possible solvent and surfactant at the optimum concentration is crucial. Evaluating methanol, ethanol, 1-propanol, DMSO and DMF at concentration ranges of 0~10% revealed < 2% methanol to be most favorable when tested for ${\beta}$-gal activity and growth inhibition of the recombinant A. tumefaciens strain. On the other hand, among surfactants tested, Triton X-100 was similarly effective in increasing the delivery of autoinducers for activity at less than 0.05% concentration.

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Preparation and Characterization of Deoxycholic Acid-Grafted Hyaluronic Acid as a Durg Carrier (약물전달체로서 디옥시콜산이 결합된 히알루론산의 제조와 특성)

  • Choi, Chang-Yong;Park, Jun-Kyu;Kim, Won-Suk;Jang, Mi-Kyeong;Nah, Jae-Woon
    • Polymer(Korea)
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    • v.35 no.2
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    • pp.119-123
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    • 2011
  • To develop hyaluronic acid (HA)-based anticancer agent carrier, hyaluronic acid was chemically modified with the hydrophobic group of deoxycholic acid(DA). The physicochemical properties of the deoxycholic acid-conjugated HA (HADA) were investigated by using $^1H$ NMR, FTIR spectrophotometer and TEM. Paclitaxel (Tx)-loaded HADA nanoparticles were prepared by a dialysis method. The loading efficiency of drug and drug contents of Tx-loaded HADA nanoparticles (HADA-Tx) were measured by HPLC. The anticancer activity of HADA-Tx was investigated by its cytotoxicity against KB cell in vitro. The HADA-Tx was shown to have the superior potential for the anticancer drug delivery.

Comparison of Analysis Methods for Detection of Replication Competent Virus and Functional Titers of HIV-l Based Lentivirus Vector (HIV-l 유래 렌티바이러스 벡터의 복제가능 바이러스 검출과 역가측정 분석방법 비교)

  • Chang Seok Kee;Oh Il Ung;Jeong Jayoung;Ahn Kwang Soo;Sohn Yeowon
    • YAKHAK HOEJI
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    • v.49 no.3
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    • pp.217-224
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    • 2005
  • Human Immunodeficiency Virus type 1 (HIV-l) based lentivirus vector has demonstrated great potential as gene therapy vectors mediating efficient gene delivery and long-term transgene expression in both dividing and nondividing cells. However, for clinical studies it must be confirmed that vector preparations are safe and not contaminated by replication competent lentivirus (RCL) related to the parental pathogenic virus, HIV-l. In this study, we would like to establish the method for titration and RCL detection of lentivirus vector. The titration was determined by vector expression containing the green fluorescent protein, GFP in transduced cells. The titer was $1{\times}10^7$ Transducing Unit/ml in the GFP expression assay and $8.9{\times}10^7$ molecules/ml in the real-time PCR. Also, for the detection of RCL, we have used a combination method of PCR and p24 antigen detection. First, PBS/psi and VSV-G region in the genomic DNA of transduced cells was detected by PCR assay. Second, transfer and expression of the HIV-1 gag gene was detected by p24 ELISA. In an attempt to amplify any RCL, the transduced cells were cultured for 3 weeks (amplification phase) and the supernatant of amplified transduced cell was used for the second transduction to determine whether a true RCL was present (indicator phase). Analysis of cells and supernatant at day 6 in indicator phase were negative for PBS/psi, VSV-G, and p24 antigen. These results suggest that they are not mobilized and therefore there are no RCL in amplification phase. Thus, real-time PCR is a reliable and sensitive method for titration and RCL detection of lentivirus vector.

Fabrication of Biodegradable Disc-shaped Microparticles with Micropattern using a Hot Embossing Process with Porous Microparticles

  • Hwang, Ji-Yea;Choy, Young-Bin;Seo, Soon-Min;Park, Jung-Hwan
    • Journal of Pharmaceutical Investigation
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    • v.41 no.3
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    • pp.147-151
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    • 2011
  • This paper demonstrates the development of a method for preparing micropatterned microdiscs in order to increase contact area with cells and to change the release pattern of drugs. The microdiscs were manufactured with hot embossing, where a polyurethane master structure was pressed onto both solid and porous microparticles made of polylactic-co-glycolic acid at various temperatures to form a micropattern on the microdiscs. Flat microdiscs were formed by hot embossing of porous microparticles; the porosity allowed space for flattening of the microdiscs. Three types of micro-grooves were patterned onto the flat microdiscs using prepared micropatterned molds: (1) 10 ${\mu}M$ deep, 5 ${\mu}M$ wide, and spaced 2 ${\mu}M$ apart; (2) 10 ${\mu}M$ deep, 9 ${\mu}M$ wide, and spaced 5 ${\mu}M$ apart; and (3) 10 ${\mu}M$ deep, 50 ${\mu}M$ wide, and spaced 50 ${\mu}M$ apart. This novel microdisc preparation method using hot embossing to create micropatterns on flattened porous microparticles provides the opportunity for low-cost, rapid manufacture of microdiscs that can be used to control cell adhesion and drug delivery rates.