• Title/Summary/Keyword: Biomedical potential

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Sex-specific differences in the association of a common aldehyde dehydrogenase 2 gene polymorphism and alcohol consumption with stroke risk in a Korean population: a prospective cohort study

  • Shin, Chol;Kwack, KyuBum;Cho, Nam H.;Kim, Seong Hwan;Baik, Inkyung
    • Nutrition Research and Practice
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    • v.9 no.1
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    • pp.79-86
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    • 2015
  • BACKGROUND/OBJECTIVES: It is well-known that alcohol consumption is associated with stroke risk as well as with aldehyde dehydrogenase 2 gene (ALDH2) polymorphisms. However, it is unclear whether ALDH2 polymorphisms are associated with stroke risk independent of alcohol consumption and whether such association is modified by sex. We evaluated sex-specific associations of a common ALDH2 polymorphism and alcohol consumption with stroke risk in a Korean population. SUBJECTS/METHODS: We conducted a prospective cohort study involving 8,465 men and women, aged 40-69 years and free of stroke between June, 2001 and January, 2003, and followed for the development of stroke. We identified new cases of stroke, which were self-reported or ascertained from vital registration data. Based on genome-wide association data, we selected a single-nucleotide polymorphism (rs2074356), which shows high linkage disequilibrium with the functional polymorphism of ALDH2. We conducted Cox proportional hazards regression analysis considering potential risk factors collected from a baseline questionnaire. RESULTS: Over the median follow-up of 8 years, 121 cases of stroke were identified. Carrying the wild-type allele of the ALDH2 polymorphism increased stroke risk among men. The multivariate hazard ratio [95% confidence interval] of stroke was 2.02 [1.03-3.99] for the wild-type allele compared with the mutant alleles, but the association was attenuated after controlling for alcohol consumption. Combinations of the wild-type allele and other risk factors of stroke, such as old age, diabetes mellitus, and habitual snoring, synergistically increased the risk among men. Among women, however, the ALDH2 polymorphism was not associated with stroke risk. CONCLUSIONS: The prospective cohort study showed a significant association between a common ALDH2 polymorphism and stroke risk in Korean men, but not in Korean women, and also demonstrated that men with genetic disadvantages gain more risk when having risk factors of stroke. Thus, these men may need to make more concerted efforts to control modifiable risk factors of stroke.

A Numerical Study on the Response of the Tibial Component in Total Knee Arthroplasty to Longitudinal Impact (인공무릎관절 전치환술에 있어 축방향 충격에 의한 Tibial Component의 응답 특성 분석 연구)

  • 조용균;조철형;최재봉;이태수;최귀원
    • Journal of Biomedical Engineering Research
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    • v.19 no.5
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    • pp.503-511
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    • 1998
  • In this study, the stress distribution for different tibial components was observed In order to Investigate the load transfer and potential failure mechanism of the tibial components subjected to dynamic impact loading and also to evacuate the effect of bone-implant bonding conditions on the implant system. The 3-dimensional finite element models included an intact tibia, cemented metal-backed tibial component, uncemented metal-blocked tibial component, cemented all-polyethylene tibial component, and metal-backed component with a debonded bone/stem interface. The results showed that the cemented metal-hocked component Induced slightly higher peak stress at stem tip than the uncemented component. The peak stress of the all-polyethylene tibia1 component at stem trip showed about half thats of metal-backed tibial components. The all-polyethylene component showed a similar dynamic response to intact tibia. In case of debonded bone/stem interface, the peak stress below the metal tray was three times Higher than that of the fully bonded interface and unstable stress distribution at the stem tip was observed with time, which causes another adverse bone apposition and implant loosening. Thus, the all-polyethylene tibial component bonded fully to the surrounding bone might be most desirable system under an impact loading.

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Dispersion of Particle Pulse in Human Lung Airway (인체기관지내의 입자펄스 확산 실험)

  • 이진원;이동엽;추경호
    • Journal of Biomedical Engineering Research
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    • v.19 no.5
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    • pp.511-518
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    • 1998
  • In order to develop the aerosol bolus technique which is thought to be a potential tool for probing geometries or abnormalities of small airways, an experimental system of measuring fast time variations of particle concentration in the inhaled and exhaled breathing air was developed. The system generates monodisperse sebacic acrid particles of 1 micron size and 1.2 of geometric standard deviation in high concentration of $10^8$ particles/cc, delivers a short pulse of particles at the controlled instant during inhalation using a solenoid valve, and measures the fast change of particle concentration in using the laser light scattering. Successful operation of the generator and the measuring system was confirmed by smooth concentration profiles in inhalation. It was also confirmed that maintaining a constant breathing rate is essential to stable outputs and any disturbance in flow rate near the mode (maximum concentration) induces a large number of spurious peaks in the exhalation. Experimental data without strict control of breathing flow rate showed a substantial amount of scatter. The measured results showed an improvement in scatter over the existing results. When compared with theoretical predictions from 1-D convective diffusion equation and other experiments, general characteristics of dispersion for several penetration depths showed a good agreement, but there exists some difference in absolute values, which is attributed to the difference in body conditions. Improvements are needed in the theory, especially in relation to correcting for the effect of breathing flow rate.

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The effect of flavonoids on the TREK-1 channel (TREK-1 채널에 대한 플라보노이드의 효과)

  • Kim, Yang-Mi;Kim, Kyung-Ah
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.12 no.6
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    • pp.2660-2667
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    • 2011
  • TREK-1 channel is a member of the two-pore domain potassium (K2P) channel family that is regulated by intracellular pH, membrane stretch, polyunsaturated fatty acids, temperature, and some neuroprotectant agents. TREK-1 channel can influence neuronal excitability by regulating leakage of potassium ions and resting membrane potential. TREK-1 channel has been shown to be overexpressed in prostate cancer cells. Although the importance of these properties, relatively little is known about flavonoid effects in the regulations of TREK-1 channel. The purpose of the study was to screening of flavonoids as the TREK-1 channel modulator using one of electrophysiological techniques such as excised inside-out patch configuration. We demonstrated blocking effect on TREK-1 channel by flavonoids such as epigallocatechin-3-gallate (EGCG), curcumin and quercetin in CHO cells transiently expressing TREK-1 channel. The inhibition of TREK-1 channel by quercetin and curcumin was reversible, whereas EGCG was little reversible. Quercetin, EGCG and curcumin decreased the relative channel activity to 73%, 91% and 94%, respectively. The half-inhibitory concentration (IC50) of curcumin, quercetin and EGCG was $1.04{\pm}0.19\;{\mu}M$, $1.13{\pm}0.26\;{\mu}M$ and $13.5{\pm}2.20\;{\mu}M$ in CHO cells expressing TREK-1 channel, respectively. These results indicate that flavonoids might regulate TREK-1 and this regulation might be one of the pharmacological actions of flavonoid in nervous systems and cancer cells.

Characterization of angiotensin II antagonism displayed by KR-31081, a novel nonpeptide AT1 receptor antagonist (안지오텐신 수용체 길항제 KR-31081의 특성에 관한 연구)

  • Lee, Sung-Hou
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.10 no.10
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    • pp.2997-3003
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    • 2009
  • The pharmacological profile of KR-31081, a nonpeptide $AT_1$ selective angiotensin receptor antagonist, was investigated by receptor binding studies, functional in vitro assays with rabbit aorta. KR-31081 inhibited the specific binding of $[^{125}I]\;[Sar^1,\;Ile^8]$-angiotensin II to human recombinant $AT_1$ receptor with an 8.6-fold greater potency than losartan ($IC_{50}$: 1.43 and 12.3 nM, respectively), but it did not inhibit the binding of [$^{125}I$] CGP 42112A to human recombinant $AT_2$ receptor ($IC_{50}$: higher than $10{\mu}M$ for both). The Hill coefficient for the competition curve of KR-31081 against $AT_1$ receptor was not significantly different from unity (0.99). Scatchard analysis showed that KR-31081 interacted with human recombinant $AT_1$ receptor in a competitive manner, as with losartan. In functional studies with rabbit aorta, KR-31081 competitively inhibited the contractile response to angiotensin II ($pK_B$ values: 8.66) with 20-70% decrease in the maximum contractile responses, unlike losartan that showed competitive antagonism without any change in the maximum contractile responses to angiotensin II ($pA_2$ values: 7.59). These results suggest that KR-31081 is a highly potent $AT_1$ selective angiotensin II receptor antagonist with a mode of insurmountable antagonism to be developed as the exploratory potential of this compound.

Association between the HSPA1B ±1267A/G Polymorphism and Cancer Risk: a Meta-analysis of 14 Case-Control Studies

  • Kuang, Dan;Chen, Wei;Song, Yue-Zhang;Yu, Yan-Yan;Zhang, Dong-Ying;Wu, Lang;Tang, Jie
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6855-6861
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    • 2014
  • Background: Previous epidemiological studies have suggested a potential role of the $HSPA1B{\pm}1267A/G$ polymorphism in risk of developing cancer. However, the results were inconsistent. Therefore, we performed this meta-analysis to summarize the possible association with cancer risk. Materials and Methods: We retrieved relevant articles from PubMed, EMBASE, ISI Web of Science, Chinese Biomedical Literature and Chinese National Knowledge Infrastructure. Studies were selected using specific criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess those associations. All analyses were performed using STATA software. Results: Fourteen case-control studies, including 1, 834 cancer cases and 2, 028 controls were included in this meta-analysis. Overall, the results indicated that the G allele of HSPA1B gene ${\pm}1267A/G$ was significantly associated with an increased cancer risk in all genetic models (G vs A: OR=1.51, 95%CI 1.17-1.95, p=0.001; GG vs AA: OR=2.93, 95%CI 1.50-5.74, p=0.002; AG vs AA: OR=1.48, 95%CI 1.10-1.98, p=0.009; GG/AG vs AA: OR=1.69, 95%CI 1.22-2.33, p=0.001; GG vs AG/AA: OR=2.31, 95%CI 1.24-4.32, p=0.009). In the subgroup analysis stratified by ethnicity, a significant association was identified in Caucasians (G vs A: OR=1.35, 95%CI 1.08-1.69, p=0.008; GG/AG vs AA: OR=1.36, 95%CI 1.09-1.70, p=0.007), but not in Asians. In the stratified analysis by cancer types, individuals with the G allele showed an increased risk of hepatocellular carcinoma compared with carriers of the A allele (OR=2.40, 95%CI 1.47-3.91, p<0.001). Inversely, individuals with the GG genotype showed a decreased risk of gastric cancer compared with carriers of the AG/GG genotypes (GG vs AG/AA: OR=0.39, 95%CI 0.20-0.70, p=0.007). Conclusions: This meta-analysis suggests associations between the HSPA1B ${\pm}1267A/G$ polymorphism and risk of cancer. However, this association might be Caucasian-specific and the G allele of this polymorphism probably increases risk of hepatocellular carcinoma while decreasing risk of gastric cancer. Further well-designed studies based on larger sample sizes are needed to validate these findings.

Role of P14 and MGMT Gene Methylation in Hepatocellular Carcinomas: a Meta-analysis

  • Li, Cheng-Cheng;Yu, Zhuang;Cui, Lian-Hua;Piao, Jin-Mei;Liu, Meng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6591-6596
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    • 2014
  • Background: This meta-analysis was performed to investigate the relationship between methylation of the P14 and O6-methylguanine-DNA methyltransferase (MGMT) genes and the risk of hepatocellular carcinoma (HCC). Materials and Methods: We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) databases to identify relevant studies that analysed HCC tissues for P14 and MGMT gene methylation status; we then performed a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to evaluate the association between gene methylation and the risk of HCC. Results: Ten studies that assessed P14 gene methylation in 630 HCC tumour tissues and nine studies analysing MGMT methylation in 497 HCC tumour tissues met our inclusion criteria. Our meta-analysis revealed that the rate of P14 methylation was significantly higher in HCCs than in adjacent tissues (OR 3.69, 95%CI 1.63-8.35, p=0.002), but there was no significant difference in MGMT methylation between HCC and adjacent tissues (OR 1.76, 95%CI 0.55-5.64, p=0.34). A subgroup analysis according to ethnicity revealed that P14 methylation was closely related to the risk of HCC in Chinese and Western individuals (Chinese, OR 7.74, 95%CI 1.36-44.04, p=0.021; Western, OR 3.60, 95%CI 1.49-8.69, p=0.004). Furthermore, MGMT methylation was not correlated with the risk of HCC in Chinese individuals (OR 2.42, 95%CI 0.76-7.73, p=0.134). The combined rate of P14 methylation was 35% (95%CI 24-48%) in HCC tumour tissues and 11% (95%CI 4-27%) in adjacent tissues, whereas the combined rate of MGMT methylation was 15% (95%CI 6-32%) in HCC and 10% (95%CI 4-22%) in adjacent tissues. Conclusions: These results suggest that the risk of HCC is related to P14 methylation, but not MGMT methylation. Therefore, P14 gene methylation may be a potential biomarker for the diagnosis of HCC.

Development of Trans-Admittance Scanner (TAS) for Breast Cancer Detection (유방암 검출을 위한 생계 어드미턴스 스캐너의 개발)

  • 이정환;오동인;이재상;우응제;서진근;권오인
    • Journal of Biomedical Engineering Research
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    • v.25 no.5
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    • pp.335-342
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    • 2004
  • This paper describes a trans-admittance scanner for breast cancer detection. A FPGA-based sinusoidal waveform generator produces a constant voltage. The voltage is applied between a hand-held electrode and a scan probe placed on the breast. The scan probe contains an 8x8 array of electrodes that are kept at the ground potential. Multi-channel precision digital ammeters using the phase-sensitive demodulation technique were developed to measure the exit current from each electrode in the array. Different regions of the breast are scanned by moving the probe on the breast. We could get trans-admittance images of resistor and saline phantoms with an anomaly inside. The images provided the information on the depth and location of the anomaly. In future studies, we need to improve the accuracy through a better calibration method. We plan to test the scanner's ability to detect a cancer lesion inside the human breast.

Development of Micro Wired pH Electrode for Real-Time Monitoring for Gastroesophageal Reflux (위식도 역류 실시간 모니터링 마이크로 와이어 pH 전극 개발)

  • Kim, Eung-Bo;Lee, Kyu-Jin;So, Sang-Kyun;Joung, Yeun-Ho;Park, Jung Ho;Kim, Nam Hee
    • Journal of Biomedical Engineering Research
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    • v.38 no.6
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    • pp.277-284
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    • 2017
  • This paper presents an implantable pH measurement electrode for wireless gastroesophageal reflux measurement. Usually, gastroesophageal reflux is diagnosed by a catheter-type wire connection between the esophagus and the diagnostic device which brings many side effects such as restriction of daily living, pain, and discomfort in the nasal cavity and pharynx of patients. In order to solve these issues, researchers have been studied a wireless measurement method and a micro-sized pH electrode for human body insertion is necessary. Commercial glass packaged pH meter is formed by a sensing and a reference electrodes in a KCl solution. However, if the glass meter is inserted into the human body, there are risks of leakage of the solution, breakage of the glass package, injury of the body elements. Therefore, the solution should be solidified on the micro-sized noble metal wire which has a characteristic of biocompatible. After solidified wire fabrication, the designed meter was tested for feasibility of measurement and the result was well agreed with pH values of commercial pH meter. Potentials in pH 1 to 12 solution was measured to obtain the sensitivity of the sensor with linearity. And we have designed a simulation of gastroesophageal reflux with symptom frequency, interval, and duration time in pH 2 solution. The proposed sensor has capable to get the same potential for 24 measurements in 3 days, and it has sensed same pH values of 2 for one hour with every 10 minutes. Furthermore, the sensor was survived for 48 hours with reasonable potentials in the acid solution.

A Novel Screening Strategy for Salt-resistant Alpha-helical Antimicrobial Peptides from a Phage Display Library (Phage Display Library를 이용한 Salt-Resistant Alpha-Helical 항균 펩타이드의 새로운 탐색방법)

  • Park, Ju-Hee;Han, Ok-Kyung;Lee, Baek-Rak;Kim, Jeong-Hyun
    • Microbiology and Biotechnology Letters
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    • v.35 no.4
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    • pp.278-284
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    • 2007
  • A novel screening strategy for salt-resistant antimicrobial peptides from a M13 peptide library was developed. Fusion of MSI-344, a magainin derivative and indolicidin to pIII coat proteins did not significantly affect viability of the recombinant phages, which indicated that the pIII could neutralize toxicity of the antimicrobial peptides and therefore it is possible to construct antimicrobial peptide library in Escherichia coli. On the basis of the conserved sequence of ${\alpha}$-helical antimicrobial peptides, a semi-combinatorial peptide library was constructed in which the peptides were displayed by pIII. To remove hemolytic activity from the library, the phages bound to red blood cells were removed, and the subtracted phage library was screened for binding to target bacteria Pseudomonas aeruginosa and Staphylococcus aureus under high salt concentrations. The screened peptides showed relatively low antimicrobial activity against the target bacteria. However, antimicrobial activities of the screened peptides P06 and S18 were not affected by the cation concentrations of 150 mM $Na^+$, 2 mM $Mg^{2+}$ and 2 mM $Ca^{2+}$ without significant hemolytic activity. This screening strategy that is based on binding capacity to target cells provides new potential to develop salt-tolerant antimicrobial peptides.