• 대한기관식도과학회지
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• 제9권1호
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• pp.60-66
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• 2003

Although there is a wide range of diseases caused by gastric acid reflux and the number of cases is on the rise, it is difficult for the laryngologist to make the correct diagnosis. The treatment for laryngopharyngeal reflux can be grouped into 3 categories - changes in lifestyle, medication, and surgery. The medication used to treat laryngopharyngeal reflux are prokinetic agents and acid supressive agents such as antacids, H2 blockers, and PPIs(Proton pump inhibitor). Rabeprazole sodium($Pariet^{\circledR}$) is a newly developed agent belonging to the PPI group, but in contrast with the existing drugs such as omeprazole, lansoprazole, pantoprazole, has a low dependency on CYP2C19 during the metabolic cycle. Thus, it is known to have a quick but fixed antiacid effect and less individual differences. We analyzed 2166 patients from 32 hospitals who were prescribed $Pariet^{\circledR}$ from May, 2001 to April, 2002. The patients were divided into 4 groups according to the duration of treatment - Group 1: 1-14 days, Group 2: 15-28 days, group 3: 29-56 days, Group 4: more than 56 days. The cases were then analyzed for improvement of 8 symptoms(heart bum, regurgitation, chronic cough, hoarseness, globus sensation, chronic throat clearing, sore throat, and dysphagia), improvement on laryngoscope, usefulness to the doctor, and complication development. Of the total of 2116 patients, 1627(75.1%) cases showed at least 50% improvement of symptoms and the amount of improvement increased according to the duration of medical treatment. Most of the patients showed objective improvement on the laryngoscope, with 32.9% showing significant improvement and 38.7% showing moderate improvement. 37.6% of the doctors questioned replied that $Pariet^{\circledR}$ was very useful and 50.3% said it was useful, showing that most were satisfied with the treatment results. The complications known to develop after taking PPI are headache, nausea, diarrhea, abdominal pain, constipation, dizziness, fatigue, and of these, only a small percentage of the patients complained of mild headache. $Pariet^{\circledR}$ has shown to be a relatively safe and effective drug for the treatment of laryngopharyngeal reflux.

• Environmental Analysis Health and Toxicology
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• 제25권3호
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• pp.241-251
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• 2010

Crucian carp (Carassius auratus) has been used as the sentinel species for POPs (Persistent Organic Pollutants) monitoring in aquatic environment. However, there is little information for dioxin toxicity and especially, early life stage toxicity in crucian carp have been never carried out. In this study, we investigated several toxic effects for 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in fertilized egg obtained by natural fertilization from crucian carp. The embryos at 3 h post-fertilization (hpf) were treated with 0.039, 0.156, 0.625, and 2.5 (${\mu}g/L$) TCDD by waterborne exposure for 60 minutes and changed with fresh water 2 times per day. Fertilized eggs started hatching at 51 hpf and TCDD exposed embryo showed decrease of hatching rate in a dose-dependent manner at 75 hpf. Pericardial edema was continuously observed in larvae exposed to TCDD from hatching start time (51 hpf), followed by the onset of mortality. In addition, AhR-related gene, CYP1A was clearly increased by TCDD in a dose dependent manner. These results indicated that fertilized eggs obtained from crucian carp have the TCDD related gene regulation and a distinct TCDD developmental toxicity syndrome by TCDD exposure. Therefore, we suggested that early life stage test in crucian carp could be used as test methods on dioxins toxicity.

• 약학회지
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• 제53권5호
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• pp.259-264
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• 2009

The present study was to investigate the effect of naringin, a flavonoid, on the pharmacokinetics of losartan in rats. Pharmacokinetic parameters of losartan in rats were determined after an oral administration of losartan (9 mg/kg) in the presence or absence of naringin (0.5, 2.5 and 10 mg/kg). The pharmacokinetic parameters of losartan were significantly altered by the presence of naringin compared with the control group (given losartan alone). Presence of naringin significantly (p<0.05, 2.5 mg/kg; p<0.01, 10 mg/kg) increased the area under the plasma concentration?time curve (AUC) of losartan by 43.7~63.0% and peak plasma concentration ($C_{max}$) of losartan by 31.7~45.5%. Consequently, the absolute bioavailability (AB) of losartan in the presence of naringin was 43.8~62.9%, which was enhanced significantly (p<0.05, p<0.01) compared to that in the oral control group (22.4%). The relative bioavailability (R.B.) of losartan increased by 1.44- to 1.63-fold in the presence of naringin. However, there was no significant change in the peak plasma concentration ($T_{max}$) and terminal half-life ($t_{1/2}$) of losartan in the presence of naringin. In conclusion, the presence of naringin significantly enhanced the oral bioavailability of losartan, implying that presence of naringin might be mainly effective to inhibit the cytochrome P450 (CYP)3A-mediated metabolism, resulting in reducing gastrointestinal and hepatic first-pass metabilism and Pglycoprotein (P-gp)-mediated efflux of losartan in small intestine. Concurrent use of naringin or naringin-containing dietary supplement with losartan should require close monitoring for potential drug interactions.

• 한국축산식품학회지
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• 제42권6호
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• pp.1046-1060
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• 2022

This study aimed to investigate the effects of the metabolites of Latilactobacillus curvatus BYB3 and indole-activated aryl hydrocarbon receptor (AhR) to increase the tight junction (TJ) proteins in an in vitro model of intestinal inflammation. In a Western blot assay, the metabolites of L. curvatus BYB3 reduced the TJ demage in lipoploysaccharide (LPS) stimulated-Caco-2 cells. This reduction was a result of upregulating the expression of TJ-associated proteins and suppressing the nuclear factor-κB signaling. Immunofluorescence images consistently revealed that LPS disrupted and reduced the expression of TJ proteins, while the metabolites of L. curvatus BYB3 and indole reversed these alterations. The protective effects of L. curvatus BYB3 were observed on the intestinal barrier function when measuring transepithelial electrical resistance. Using high-performance liquid chromatography analysis the metabolites, the indole-3-latic acid and indole-3-acetamide concentrations were found to be 1.73±0.27 mg/L and 0.51±0.39 mg/L, respectively. These findings indicate that the metabolites of L. curvatus BYB3 have increasing mRNA expressions of cytochrome P450 1A1 (CYP1A1) and AhR, and may thus be applicable for therapy of various inflammatory gut diseases as postbiotics.

• 대한소아치과학회지
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• 제33권1호
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• pp.43-52
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• 2006

소아의 치아우식증을 예방하기 위한 불소의 국소도포는 소아치과 영역에서 널리 시행되고 있다. 하지만 이러한 잇점에도 불구하고 최근 수복물 표면을 거칠게 한다는 부작용에 대해 논란이 되고 있다. 이에 본 연구에서는 불소도포가 심미 수복물의 표면변화에 미치는 영향을 평가하기 위해 수종의 복합레진에 국소도포용 불소젤을 도포시킨 후 변화를 관찰하였다. 시판용 레진인 Z 250(3M ESPE, USA) Ultraseal $XT^{(R)}$(Ultradent, USA), Filtek $flow^{(R)}$(3M, USA), $Revolution^{(R)}$(Kerr, USA), Denfil(Vericom, Korea)를 이용하여 시편을 제작하고, 불소젤은 $Topex^{(R)}$(Sultan Dental Products, Canada)을 각각 1분과 4분 동안 도포시켰다. 각 제품마다 불소젤을 도포하지 않은 5개의 시편을 대조군으로 사용하였다. 그 후 이 시편들의 표면 거칠기$(R_a\;value,\;{\mu}m)$와 무게 차이를 측정하고 주사전자현미경을 이용하여 다음과 같은 결과를 얻었다. 1. 불소젤을 도포시키지 않은 대조군에서 가장 평활한 표면을 보였으며 1분군, 4분군 순으로 표면 거칠기가 증가하였다. 그리고 Revolution을 제외한 모든 제품에서 유의한 차이를 보였다(p<0.05). 2. 국소도포용 불소젤을 도포한 각 레진 시편의 무게 차이를 비교한 결과 대조군, 1분군, 4분군 간에 유의한 차이는 없었다(p>0.05). 3. 주사전자현미경 관찰시 불소젤에 도포시킨 실험군은 대조군에 비해 거친 표면을 나타냈다. 이상의 결과로 국소적 불소도포는 복합레진의 표면 거칠기에 영향을 미치며 이를 고려하여 사용한다면 4분보다는 1분간의 불소도포법을 이용하는 것을 추천할 수 있을 것으로 사료된다.대구치의 원심경사는 필연적으로 일어나며, 이를 최소화하기 위한 노력이 계속되어야 할 것으로 사료된다.글래스 아이오노머 시멘트 사이에는 유의한 차이가 없었다.착제의 종류에 따른 전단결합강도를 비교한 결과, 영구치와 유치 모두에서 Clearfil SE Bond를 사용한 군의 전단결합강도가 가장 높았으며 AQ Bond를 사용한 군의 전단결합강도가 가장 낮았다.본에서 III군에 비해 크기가 큰 기포가 더욱 많이 관찰되었다.e의 약동학은 cimetidine에 의해 유의한 차이를 보였으며 CYP1A2유전자형에 따른 영향은 관찰할 수 없었다. CYP1A2유전자형에 따른 생체내 대사능을 관찰하는 실험이 향후 이루어 져야 할 것으로 사료된다.san film보다 큰 수증기 투과도를 보였다.적으로 유의한 차이를 보이지 않았다.y tissue layer thinning은 3 군모두에서 관찰되었고 항암 3 일군이 가장 심하게 나타났다. 이상의 실험결과를 보면 술전 항암제투여가 초기에 시행한 경우에는 조직의 치유에 초기 5 일정도까지는 영향을 미치나 7 일이 지나면 정상범주로 회복함을 알수 있었고 실험결과 항암제 투여후 3 일째 피판 형성한 군에서 피판치유가 늦어진 것으로 관찰되어 인체에서 항암 투여후 수술시기는 인체면역계가 회복하는 시기를 3주이상 경과후 적어도 4주째 수술시기를 정하는 것이 유리하리라 생각되었다.한 복합레진은 개발의 초기단계이며, 물성의 증가를 위한 연구가 필요할 것으로 사료된다.또 다른 약물인 glycyrrhetinic acid($100{\mu}M$)도 CCh 자극으로 인한 타액분비를 억제하였다. 이상의 결과로 미루어 gap junction은 흰쥐 악하선 세포로부터의 타액분비 조절에 중요한 역할을 하는데, 이는 gap junction이 세포막 $Ca^{2+}$ 통로를 조절함으로써 수용체 자극으로 유발된 세포내 $Ca^{2+}$ 농도 변화에

• 대한기관식도과학회:학술대회논문집
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• 대한기관식도과학회 2002년도 제2차 추계학술대회
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• pp.9-9
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• 2002

이비인후과 영역에 있어서 위산 역류에 의한 질환의 진단은 쉽지 않고 분명하지 않은 점이 많지만, 병변의 영향은 광범위하며, 실제로 역류에 의한 증상을 가지고 내원하는 환자도 증가하는 추세이다. 인후두역류질환의 치료는 크게 생활습관의 변경, 약물복용, 항역류수술로 나눌 수 있으며, 사용약제는 크게 두 부류로 나누는데, 제산제, H2 수용체 차단제, PPI(Proton Pump Inhibitor) 제제와 같은 산억제 약물군과 Prokinetic 약물군이다. Rabeprazole sodium(Pariet(R))은 PPI 제제에 해당하는 약제로 기존의 omeprazole, lansoprazole, pantoprazole과는 달리 대사 과정 중 CYP2C19에 대한 의존도가 낮아, 개체 간 차이가 적고 빠르고 일정하게 산분비 억제 효과를 나타내는 것으로 알려져 있은 약물이다. 2001년 5월부터 2002년 4월까지 32개 병원에서 Pariet(R) 를 복용한 2166명의 환자를 대상으로 분석하였다. 복용기간에 따라 4군(1군;1-14일, 2군;15-28일, 3군;29-56일, 4군:57일 이상)으로 나누었으며, 8가지 증상(Heart burn, Regurgitation, Chronic cough, Hoarseness, Globus sensation, Chronic throat clearing, Sore throat, Dysphagia)에 대한 호전 여부 및 후두내시경상 개선 정도, 의사에 의한 유용도 평가, 부작용 발생 여부에 대해 연구하였다. 증상개선율 50%이상을 치료 반응군으로 했을때 전체 2166명중 1627명(75.1%)에서 증상의 호전을 보았으며, 이는 복용기간이 길수록 증가하였다. 후두 내시경상 개선 정도는 현저한 개선이 32.9%, 중등도 개선이 38.7%로 대부분 환자에서 객관적인 병변의 호전을 보였으며, 유용도 평가에서는 매우 유용이 37.6%, 유용이 50.3%로 치료효과에 대한 만족도도 높은 것을 알수 있었다. PPI 제제의 부작용으로 보고되고 있는 두통, 오심, 설사, 복통. 변비, 어지럼증. 피곤 중. 소수의 환자가 두통을 호소하였으나, 그다지 심각한 정도는 아니었다. 인후두역류증 치료제로서 Pariet(R) 는 비교적 안전하고 효과가 높은 약물임이 임상 연구 결과 밝혀졌기에 보고하는 바이다.

• Journal of Plant Biotechnology
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• 제49권4호
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• pp.307-315
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• 2022

개똥쑥은 말라리아 등 다양한 질병의 치료물질인 artemisinin 제공하나, 식물체 내 농도가 낮고, 생산이 불안정하여 국제적 수요에 대응하지 못하고 있다. 재배환경을 인공적으로 제어하는 식물공장 시스템은 계절이나 장소에 제한 없이 약용식물의 공장식 생산체계가 가능하다(Kim 2010). 본 연구에서는 식물공장에서 개똥쑥의 artemisinin의 대량생산이 가능한 최적의 조건을 찾기 위하여 파종부터 수확까지 적색광(R)과 청색광(B)을 혼합한 3종류의 LED (R : B = 6 : 4, 7 : 3, 8 : 2)에서 생장 및 물질생산에 적합한 광조건을 탐색하였다. 개똥쑥의 수확 전, 1,395 ㎼/cm²의 UV-B, 4℃의 저온, 그리고 건조 처리로 식물에 hormesis를 유도하여 artemisinin의 생산 증가를 확인하였다. Artemisinin 생합성에 관여하는 효소들 중에서 ADS, CYP, ALDH1의 발현량을 qPCR로 측정하였고, artemisinin 정량을 통해 전사체와 대사물질의 연관성을 확인하고, artemisinin 생산에 적합한 재배 광조건과 hormesis 처리 조건을 탐색하였다. 3종의 LED 비율 중 8 : 2에서 높은 생체중 및 건물중을 생산했으며, hormesis를 유도하기 위한 3종의 물리 처리에서 이를 통해 7 : 3 식물을 수확전 6시간 건조처리했을 때 artemisinin 함량이 약 2배 증가하였다.

• 수산해양기술연구
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• 제54권1호
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• pp.38-53
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• 2018

The purpose of this study is to estimate potential yield (PY) for Korean west coast fisheries using the holistic production method (HPM). HPM involves the use of surplus production models to apply input data of catch and standardized fishing efforts. HPM compared the estimated parameters of the surplus production from four different models: the Fox model, CYP model, ASPIC model, and maximum entropy model. The PY estimates ranged from 174,232 metric tons (mt) using the CYP model to 238,088 mt using the maximum entropy model. The highest coefficient of determination ($R^2$), the lowest root mean square error (RMSE), and the lowest Theil's U statistic (U) for Korean west coast fisheries were obtained from the maximum entropy model. The maximum entropy model showed relatively better fits of data, indicating that the maximum entropy model is statistically more stable and accurate than other models. The estimate from the maximum entropy model is regarded as a more reasonable estimate of PY. The quality of input data should be improved for the future study of PY to obtain more reliable estimates.

• Biomolecules & Therapeutics
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• 제29권2호
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• pp.227-233
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• 2021

Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon and ubiquitous environmental toxin with known harmful effects to human health. Abnormal phenotypes of keratinocytes are closely associated with their exposure to B[a]P. Resorcinol is a component of argan oil with reported anticancer activities, but its mechanism of action and potential effect on B[a]P damage to the skin is unknown. In this study, we investigated the effects of resorcinol on B[a]P-induced abnormal keratinocyte biology and its mechanisms of action in human epidermal keratinocyte cell line HaCaT. Resorcinol suppressed aryl hydrocarbon receptor (AhR) activity as evidenced by the inhibition of B[a]P-induced xenobiotic response element (XRE)-reporter activation and cytochrome P450 1A1 (CYP1A1) expression. In addition, resorcinol attenuated B[a]P-induced nuclear translocation of AhR, and production of ROS and pro-inflammatory cytokines. We also found that resorcinol increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activity. Antioxidant response element (ARE)-reporter activity and expression of ARE-dependent genes NAD(P)H dehydrogenase [quinone] 1 (NQO1), heme oxygenase-1 (HO-1) were increased by resorcinol. Consistently, resorcinol treatment induced nuclear localization of Nrf2 as seen by Western analysis. Knockdown of Nrf2 attenuated the resorcinol effects on ARE signaling, but knockdown of AhR did not affect resorcinol activation of Nrf2. This suggests that activation of antioxidant activity by resorcinol is not mediated by AhR. These results indicate that resorcinol is protective against effects of B[a]P exposure. The mechanism of action of resorcinol is inhibition of AhR and activation of Nrf2-mediated antioxidant signaling. Our findings suggest that resorcinol may have potential as a protective agent against B[a]P-containing pollutants.

• 한국환경성돌연변이발암원학회지
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• 제23권2호
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• pp.56-62
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• 2003

The liver progenitor cells could form a potential target cell population fore both tumor-initiating and -promoting chemicals. Induction of drug-metabolizing and antioxidant enzymes, including AhR-dependent CYP1A1, NQO-1 and AKR1C9, was detected in the rat liver epithelial WB-F344 "stem-like" cells. Additionally, WB-F344 cells express a functional, wild-type form of p53 protein, a biomarker of genotoxic events, and connexin 43, a basic structural unit of gap junctions forming an important type of intercellular communication. In this cellular model, two complementary assays have been established for detection of the modes of action associated with tumor promotion: inhibition of gap junctional intercellular communication (GJIC) and proliferative activity in confluent cells. We found that the PAHs and PCBs, which are AhR agonists, released WB-F344 cells from contact inhibition, increasing both DNA synthesis and cell numbers. Genotoxic effects of some PAHs that lead to apoptosis and cell cycle delay might interfere with the proliferative activity of PAHs. Contrary to that, the nongenotoxic low-molecular-weight PAHs and non-dioxin-like PCB congeners, abundant in the environment, did not significantly affect cell cycle and cell proliferation; however both groups of compounds inhibited GJIC in WB-F344 cells. The release from contact inhibiton by a mechanism that possibly involves the AhR activation, inhibition of GJIC and genotoxic events induced by environmental contaminants are three important modes of action that could play an important role in carcinogenic effects of toxic compounds. The relative potencies to inhibit GJIC, to induce AhR-mediated activity, and to release cells from contact inhibition were determined for a large series of PAHs and PCBs and their metabolites. In vitro bioassays based on detection of events on cellular level (deregulation of GJIC and/or proliferation) or determination of receptor-mediated activities in both ?$stem-like^{\circ}{\times}$ and hepatocyte-like liver cellular models are valuable tools for detection of modes of action of polyaromatic hydrocarbons. They may serve, together with concentration data, as a first step in their risk assessment.