• 제목/요약/키워드: Phase II study

검색결과 699건 처리시간 0.035초

Therapeutic Effects and Adverse Drug Reactions are Affected by Icotinib Exposure and CYP2C19 and EGFR Genotypes in Chinese Non-Small Cell Lung Cancer Patients

  • Chen, Jia;Zheng, Xin;Liu, Dong-Yang;Zhao, Qian;Wu, Yi-Wen;Tan, Fen-Lai;Wang, Yin-Xiang;Jiang, Ji;Hu, Pei
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권17호
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    • pp.7195-7200
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    • 2014
  • Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

Survival Benefit of Perioperative Chemotherapy in Patients with Locally Advanced Gastric Cancer: a Propensity Score Matched Analysis

  • Eom, Bang Wool;Kim, Sohee;Kim, Ja Yeon;Yoon, Hong Man;Kim, Mi-Jung;Nam, Byung-Ho;Kim, Young-Woo;Park, Young-Iee;Park, Sook Ryun;Ryu, Keun Won
    • Journal of Gastric Cancer
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    • 제18권1호
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    • pp.69-81
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    • 2018
  • Purpose: It has been reported that the survival of patients with locally advanced gastric cancer (LAGC) is better in East Asia countries than in developed western countries; however, the prognosis of LAGC remains poor. This study aimed to evaluate the effects of perioperative chemotherapy on the long-term survival of East Asia patients with LAGC. Materials and Methods: From October 2006 through August 2008, 43 patients with LAGC received perioperative S-1 combined with weekly docetaxel in a phase II study (neoadjuvant group). These patients were matched using propensity scores to patients who underwent surgery without neoadjuvant chemotherapy during the same period (surgery group). The surgical outcomes and long-term survivals were compared between the 2 groups. Results: After matching, 43 and 86 patients were included in the neoadjuvant and surgery groups, respectively, and there was no significant difference in their baseline characteristics. Although the operating time was longer in the neoadjuvant group, there was no significant difference in postoperative complications between the 2 groups. The neoadjuvant group had a significantly higher 5-year overall survival (OS) rate (73.3% vs. 51.1%, P=0.005) and a trend towards higher 5-year progression-free survival (PFS) (62.8% vs. 49.9%, P=0.145). In the multivariate analysis, perioperative chemotherapy was an independent factor for OS, with a hazard ratio of 0.4 (P=0.005) and a marginal effect on the PFS (P=0.054). Conclusions: Perioperative chemotherapy was associated with better long-term survival without increasing postoperative complications in the setting of D2 surgery for patients with LAGC, suggesting that perioperative chemotherapy can be a therapeutic option in East Asia countries.

한국인 기관지 천식 환자에서 허설변증과 Glutathione-S-Transferase 유전자의 다형성 연구 (Association Study of Glutathione-S-Transferase M1/T1 Gene Polymorphism with Deficiency-Excess Differentiation-syndrome in Korean Bronchial Asthmatics)

  • 유승렬;정승연;정주호;김진주;정승기
    • 대한한방내과학회지
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    • 제28권3호
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    • pp.453-463
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    • 2007
  • Backgrounds : Glutathione-s-transferase (GST) is a kind of phase II metabolism enzyme and plays an important role in the detoxification of various toxic chemicals. It was reported that the genetic polymorphism of GSTM1 and GSTT1 genes may be responsible for asthma development and susceptibility to allergy. Traditional oriental medicine uses a unique diagnostic technique. differentiation-syndrome. to analyze signs and symptoms of patients synthetically. Through differentiation-syndrome. asthma patients can be divided into two groups: the deficiency syndrome group (DSG) and the excess syndrome group (ESG). Objectives : The purpose of this study was to investigate the possible association of GST gene polymorphism with clinical phenotype by differentiation-syndrome of bronchial asthma patients. Materials and Methods : One hundred and ten participants were evaluated by pulmonary function test. Patients with 53 DSG and 31 ESG by differentiation-syndrome were assessed for genetic analysis. GSTM1 and GSTT1 deletion polymorphism was performed by polymerase chain reaction (PCR). Results : GSTM1 gene deletion was detected in 43.4% of individuals in the DSG and in 38.71 % in the ESG. The distribution of GSTM1 polymorphism between DSG and ESG was not significantly different [$x^2$=0.1767, p=0.6742; OR(95% CI)=1.2139(0.4915-2.9979)]. The proportion of GSTT1 null genotypes was 41.51% in the DGS and 45.16% in the ESG. The distribution of GSTT1 polymorphism between DSG and ESG was also not significantly different [$x^2$=0.1065, p=0.7442; OR(95% CI)=0.8618(0.3525-2.1065)]. In the combined analysis of GSTM1 and GSTT1 genes, the frequency of both null type of GSTM1/GSTT1 genes was not significantly different from both positive type of GSTM1/GSTT1 genes[$x^2$=0.0768, p=0.7817; OR(95% CI)=1.2000(0.3303-4.3602)] Conclusions : These results indicate that polymorphism of the GST gene might not be associated with the symptomatic classification of DSG and ESG by differentiation-syndrome in Korean asthmatics.

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Study on Retardation Effect of a Heavy Metal in Sandy Soils

  • Kim, Dong-Ju;Sung, Baek-Doo
    • 한국지하수토양환경학회:학술대회논문집
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    • 한국지하수토양환경학회 1998년도 총회 및 춘계 학술발표회 논문집
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    • pp.43-49
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    • 1998
  • Retardation effect of heavy metals in soils caused by adsorption onto the surfaces of solids particles is well known phenomena. The adsorption of metal ions has been recognized more strong in clay mineral and organic matter contents rather than sands and gravels. In this study, we investigated the retardation effect in two sandy soils by conducting batch and column tests. The column tests were conducted to obtain the relationship between concentration and time known as breakthrough curve (BTC). We applied pulse type injection of ZnCl$_2$solution on the inlet boundary and monitored the effluent concentration at the exit boundary under steady state condition using EC-meter and ICP-AES. Batch test consisted of an equilibrium procedure for fine fractions collected from two sandy soils for various initial ZnCl$_2$concentrations, and analysis of Zn ions in equilibrated solution using ICP-AES. The results of column test showed that i) the peak concentration of Zn analyzed by ICP was far less than that detected by EC-meter for both soils and ii) travel times for peak concentration were more less identical for two different monitoring techniques. The first result can be explained by ion exchange between Zn and other cations initially present in the soil particles since ICP analysis showed a significant amount of Ca, Mg ions in the effluent. From the second result, we found that retardation effect was not present in these soils due to strong cation exchange capacity of Zn ion over other cations since we did not apply a solution containing more adsorptive cations such as Al. The result of batch test also showed high distribution coefficients (K$_{d}$) for two soils supporting the dominant ion exchange phenomena. Based on the retardation factor obtained from the Kd, we predicted the BTC using CDE model and compared with the BTC of Zn concentration obtained from ICP The predicted BTC, however, disagreed with the monitored in terms of travel time and magnitude of the peak concentrations. The only way to describe the prominent decrease of Zn ion was to introduce decay or sink coefficient in the CDE model to account for irreversible decrease of Zn ions in liquid phase.e.

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황해 연안습지 생태계 보전을 위한 초국경협력 방향 - 갯벌의 세계자연유산 등재를 중심으로 - (Pan-Yellow Sea Cooperation for the Conservation of Ecosystems in Coastal Wetlands of Yellow Sea - Focusing on the World Natural Heritage of coastal wetland-)

  • 최현아;한동욱
    • 한국습지학회지
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    • 제25권3호
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    • pp.213-219
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    • 2023
  • 기후변화 위기상황에서 습지 생태계의 기후변화 완화 및 적응 기능이 더욱 강조되고 있으며, 탄소흡수원으로서 갯벌의 생태계 서비스가 중요시되고 있다. 현재 황해지역 갯벌 중 남한과 중국의 경우 UNESCO 세계자연유산 2단계 등재를 위한 준비를 하고 있으며, 향후 황해지역 갯벌을 통한 남북한 및 중국의 초국경협력이 기대되는 상황이다. 그러나 이동성 조류 서식지, 휴식지, 중간기착지로서 황해지역 갯벌의 중요성과 보전, 관리, 남북한 및 중국의 협력체계에 관한 연구는 부족한 상황이다. 이에 본 연구에서는 UNESCO 세계자연유산으로 등재된 남한의 서남해안 갯벌과 중국의 옌청자연보호구, 잠정목록에 등재된 북한의 문덕 습지보호구를 포함한 황해지역 갯벌을 중심으로 남북한 및 중국의 생태계 보전 협력 여건을 분석하였다. 이를 바탕으로 이동성 조류 서식지, 휴식지, 중간기착지로서 황해지역 갯벌의 중요성과 황해 연안습지 주요 특징, 북한과의 협력여건 등을 분석하여 황해 연안습지의 초국경보전지역 등재를 위한 생태계 보전 협력 방향을 제시하였다

Improvement of Reproductive Efficiency of Artificial Insemination Following Estrus Induction in Dog II. Semen Freezing and Artificial Insemination in Dog

  • Lee, Y. R.;S. Y. Choe
    • 한국수정란이식학회:학술대회논문집
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    • 한국수정란이식학회 2002년도 국제심포지엄
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    • pp.92-92
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    • 2002
  • Considerable attention has been focused on the cryopreservation of semen and estrus induction in dog, as consequence of poor productivity caused by long anestrus period, in order to enhance the productivity of youngs and to preserve the breeds. The objectives of this study were to evaluate semen quality after cryopreservation and to evaluate the Pregnancy rate after insemination (AI). Fifty infertilie dogs (age 2∼3 years) were selected for the study and divided into three different estrus induction treatment groups. Group 1: dogs (n=15) were given clomifene (0.1 mg/kg) orally for five days at 12 hr intervals. Group 2: dogs (n=15) were given bromocriptine (50 $\mu\textrm{g}$/kg) orally for five days at 12 hr intervals, followed by single injection intravenously of 500 IU GnRH (Group 3, n=20) when pro-estrus occurred. The rates of pregnancy in estrus inducted dogs mated naturally compared to those inseminated artificially with ejaculated fresh semen and frozen-thawed semen. Estrus detection was performed using the method of vaginal smear and confirmed by the plasma progesterone assay. The ejaculated semen to freeze was exposed to a mixture of Tris extender with cryoprotectant (Trisma, 81 mM: TES, 209 mM: citric acid, 6 mM; glucose, 5 mM; glycerol, 8%) and cryopreserved gradually by slow-cooling at 17 cm above the surface of liquid nitrogen (LN$_2$) for 23 min. The motility of frozen-thawed spermatozoa was assessed by phase-contrast microscopy. To assess their viability and acrosome content, spermatozoa were stained with a vital stain and Fluorescence conjugated lectin Pisum Savitum Agglutinin (FITC/PAS), respectively. Pregnancy was confirmed by ultrasonograpy on day 25, 35 and 55 post insemination. The use of fresh semen, the pregnancy rates were observed 66.6, 66.6, 75.0 and 83.3% in natural estrus, clomifene induced, bromocriptine induced and a combination of GnRH and bromocriptine, respectively. The use of frozen-thawed semen, the pregnancy rates were observed 66.6, 33.3, 50.0 and 60.0% in natural estrus, clomifene induced, bromocriptine induced and a combination of GnRH and bromocriptine, respectively. No difference was observed in the number of offspring produced among natural estrus and treated groups inseminated with fresh or frozen-thawed semen. In conclusion, the pregnancy rate of dogs treated with a combination of GnRH and bromocriptine was more effective than use of clomifene or bromocriptine only. In addition, frozen-thawed semen can be used successfully far artificial insemination in dog.

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자궁내막증 환자의 복강 액내 IL-6와 TNF-α의 변화 양상에 관한 연구 (A Study of Altered IL-6 and TNF-α Expression in Peritoneal Fluid of Patients with Endometriosis)

  • 강정배;이영경
    • Clinical and Experimental Reproductive Medicine
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    • 제33권1호
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    • pp.45-52
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    • 2006
  • 목 적: 자궁내막증과 이로 인한 불임의 원인인 면역학적 인자 중 세포-매개성 면역계의 변화 양상을 규명하기 위하여 자궁내막증 환자와 자궁내막중이 없는 환자의 복강 액을 채취하여 면역 세포의 분포양상을 비교 분석하고자 IL-6와 TNF-${\alpha}$를 측정하였다. 연구방법: 자궁내막증으로 육안적 또는 조직검사로 확진된 환자 또는 불임검사를 위해 진단적 복강경을 시행한 34명을 연구군으로 등록하였으며 본 연구 이전에 자궁내막증과 관련된 어떠한 치료도 받은 적이 없거나 복강경 시술이나 개복수술과정에서 자궁내막증 소견과 증상이 없는 환자 37명을 대조군으로 하였다. 두 군의 복강 액을 추출한 다음 30분 이내에 $400g{\times}10$분 동안 원심분리 후 상층액만 검사용기에 모아 밀봉한 후 $-70^{\circ}C$ 냉동실에 보관하여 IL-6와 TNF-${\alpha}$의 농도를 "sandwich" enzyme-linked immunosorbent assays (ELISA: R & D Systems, Minnepolis, MN)로 측정하였다. 결 과: 1. 복강 액의 IL-6의 농도는 자궁내막증으로 확진된 연구군에서는 $38.9{\pm}19.7pg/ml$으로 대조군의 $22.4{\pm}10.2pg/ml$보다 유의하게 증가하였고 (p=0.02), TNF-${\alpha}$의 농도도 자궁내막증이 있는 여성에서 $20.6{\pm}8.6pg/ml$로 대조군의 $6.2{\pm}3.5pg/ml$보다 유의하게 증가하였다 (p=0.01). 2. 자궁내막증여성의 생리주기별 농도에서 IL-6은 증식기보다 분비기에 유의하게 증가한 반면 (p=0.01), TNF-${\alpha}$는 차이가 없었다 (p>0.05). 3. IL-6은 가임여성보다 불임여성에서 유의하게 증가하였고 (p=0.03), TNF-${\alpha}$는 두 군 간에 유의한 차이는 없었다 (p>0.05). 4. IL-6과 TNF-${\alpha}$ 모두 대조군과 자궁내막증 병기 I과 II는 통계학적인 유의성은 없었으나 병기 III과 IV는 유의하게 증가하였다 (p<0.05). 결 론: 자궁내막증인 환자의 복강 액에서 IL-6와 TNF-${\alpha}$가 증가하여 자궁내막증의 생성과 유지, 증상발현에 관여하며 불임의 유발 요인으로 여겨지나 향후 많은 환자를 대상으로 한 연구와 자궁내막증과 각종 cytokine과의 상호 연관관계에 대한 연구가 더 많이 필요하리라 사료된다.

학교급식에 Cook/Chill System 적용을 위한 품질보증연구(II) - 돼지불고기 - (A Quality Assurance Study for the Application of Cook/Chill System in School Foodservice Operation (II) - Pork Bulgogi (Broiled Sliced Pork with Sauces) -)

  • 곽동경;문혜경;박혜원;홍완수;류경;장혜자;김성희;최은정
    • 한국식품위생안전성학회지
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    • 제13권4호
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    • pp.319-331
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    • 1998
  • 본 연구는 학교급식에서 Cook/chill system으로 생산 가능한 음식으로 돼지 불고기를 선정하고 모의실험을 통해 급식생산체계를 반복 실시함으로서 식품 위해 분석 중요관리점(HACCP)을 규명하고, 저장기간중의 음식품질 평가를 통해 합리적인 저장기한을 설정하고자 수행되었으며, 그 연구결과는 다음과 같다. 돼지불고기는 냉동상태로 운반되지 않아 온도상승이 일어난 검수 단계를 제외하면 각 생산 단계별 기준이 준수된 양호한 상태 하에서 생산된 것으로 나타난다. 생산단계별 미생물 분석결과, 원재료($4.26{\pm}0.11\;Log\;CFU/g$)에서 중온균수가 조리하지 않은 식품 기준 이내이나 다소 높게 나타났고, 양념장($5.97{\pm}0.04\;Log\;CFU/g$)에서는 조리하지 않은 식품 기준에 근접한 수준이었으며, 양념으로 재우는 과정($5.56{\pm}0.21\;Log\;CFU/g$)도 위험 수준이었다. 가열 조리 후 최종 음식온도가 $8.25{\pm}3.54^{\circ}C$에 도달하였으나 중온균수($5.17{\pm}0.04\;Log\;CFU/g$)가 급식 단계 음식기준을 초과한 위험한 수준이었고, 기타 미생물은 검출되지 않았다. 급속 냉각과 저장 1일, 3일, 5일 동안도 중온균수가 급식단계 음식 기준에 근접한 위험한 상태였고 기타 미생물은 검출되지 않았다. 재가열 처리에 의해 저장 1일($4.62{\pm}0.22\;Log\;CFU/g$), 3일($4.55{\pm}0.20\;Log\;CFU/g$), 5일($4.25{\pm}0.16\;Log\;CFU/g$) 모두 중온균수는 감소하여 급식단계 음식기준에 충족한 상태가 되었다. 배분 3조건에서도 급식단계 음식 기준 이내에 들었다. 저장 5일간 이화학 분석 결과 pH, 산가, 휘발성 염기 질소 모두 저장 5일에 유의적으로 증가하였고, 관능평가에서는 모든 항목들이 유의적인 차이를 보이지 않았다. 티아민 정량 분속 결과 ,가열 전의 티아민 함량을 100%으로 했을 때, 가열 후에는 78.6%로 손실이 일어났으며, 냉각과 저장 1일, 3일은 티아민 손실을 거의 일으키지 않는 것으로 나타났다. 그러나 저장 5일에는 티아민이 현저히 저하되어 62.5% 보유에 그쳤다. 저장기간에 따른 미생물적, 이화학적, 관능적 품질을 분석한 결과와 티아민 함량의 변화를 고려하여 돼지불고기의 저장기한을 3일로 제안하며, 생산 단계별 온도-소요시간 측정 및 미생물 분석을 통해 규명된 중요관리점은 돼지고기와 양념장재료인 파, 마늘, 생강의 구입 및 검수, 가열조리, 냉각, 저장, 재가열과 배식단계였다.

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항 Methicillin Resistant Staphylococcus aureus 활성을 가지는 해양미생물 Pseudomonas sp. YJ-1의 분리와 특성 (Isolation and Characterization of a Marine Bacterium, Pseudomonas sp. YJ-1 with Anti-Methicillin Resistant Staphylococcus aureus Activity)

  • 우예주;정성윤
    • 환경생물
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    • 제35권4호
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    • pp.694-705
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    • 2017
  • 본 연구의 목적은 항 methicillin-resistant Staphylococcus aureus (MRSA) 활성을 가지는 해양미생물을 분리, 동정하고 항MRSA 물질을 분리 정제하여 그 물질의 활성과 시너지 효과를 밝히는 것이다. 본 연구에서 분리한 해양미생물 중에서, YJ-1 분리 균주가 가장 강한 항MRSA 활성을 나타내었다. YJ-1 균주는 생화학적 특성과 16S rRNA 유전자 염기서열에 기초하여 분류 동정되었다. YJ-1 균주의 염기서열은 Pseudomonas stutzeri와 99.2%의 상동성을 나타내어, Pseudomonas sp. YJ-1이라 명명하였다. 이 균주의 최적 성장조건은 $25^{\circ}C$와 초기 pH 농도 7.0이었다. 항MRSA 물질들을 분리정제하기 위하여 YJ-1 균주를 PPES-II 배지에 배양하였으며, 배양 상등액을 ethyl acetate, hexane과 80% MeOH로 순차적으로 추출하였다. 활성을 보인 80% MeOH 분획을 $C_{18}$ ODS 칼럼 크로마토그래피, silica gel 크로마토그래피와 역상 HPLC법으로 순차적으로 정제하여 항MRSA 활성을 가지는 3개의 순수물질 MR1, MR2 및 MR3를 얻었다. $250{\mu}g\;mL^{-1}$ 농도의 MR1 물질을 MRSA 세포에 접종했을 때, MRSA 세포의 95%가 48시간 이내에 사멸하였다. 활성을 vancomycin 및 ampicillin과 비교해 보아도, MR1 물질은 보다 우수한 항MRSA 활성을 나타내었다. 또한 항MRSA 활성은 투여량과 시간에 비례하여 증가하였다. 더욱이 MR1 물질과 vancomycin을 조합하여 시너지 효과를 보았을 때, MR1 물질을 단독으로 투여했을 때보다 신속한 MRSA 세포의 감소를 관찰할 수 있었다. 이상의 결과를 종합해보면, MRSA 감염에 있어서 Pseudomonas sp. YJ-1과 이것이 생산하는 항MRSA 물질은 천연 항균제로서 기여할 수 있으리라 판단된다.

Surface characteristics of thermally treated titanium surfaces

  • Lee, Yang-Jin;Cui, De-Zhe;Jeon, Ha-Ra;Chung, Hyun-Ju;Park, Yeong-Joon;Kim, Ok-Su;Kim, Young-Joon
    • Journal of Periodontal and Implant Science
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    • 제42권3호
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    • pp.81-87
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    • 2012
  • Purpose: The characteristics of oxidized titanium (Ti) surfaces varied according to treatment conditions such as duration time and temperature. Thermal oxidation can change Ti surface characteristics, which affect many cellular responses such as cell adhesion, proliferation, and differentiation. Thus, this study was conducted to evaluate the surface characteristics and cell response of thermally treated Ti surfaces. Methods: The samples were divided into 4 groups. Control: machined smooth titanium (Ti-S) was untreated. Group I: Ti-S was treated in a furnace at $300^{\circ}C$ for 30 minutes. Group II: Ti-S was treated at $500^{\circ}C$ for 30 minutes. Group III: Ti-S was treated at $750^{\circ}C$ for 30 minutes. A scanning electron microscope, atomic force microscope, and X-ray diffraction were used to assess surface characteristics and chemical composition. The water contact angle and surface energy were measured to assess physical properties. Results: The titanium dioxide ($TiO_2$) thickness increased as the treatment temperature increased. Additional peaks belonging to rutile $TiO_2$ were only found in group III. The contact angle in group III was significantly lower than any of the other groups. The surface energy significantly increased as the treatment temperature increased, especially in group III. In the 3-(4,5-Dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay, after 24 hours of incubation, the assessment of cell viability showed that the optical density of the control had a higher tendency than any other group, but there was no significant difference. However, the alkaline phosphatase activity increased as the temperature increased, especially in group III. Conclusions: Consequently, the surface characteristics and biocompatibility increased as the temperature increased. This indicates that surface modification by thermal treatment could be another useful method for medical and dental implants.