• 대한환경공학회지
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• 제34권3호
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• pp.195-203
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• 2012

재질별 생물활성탄(BAC) 및 안트라사이트 biofilter에서 EBCT 및 수온변화에 따른 인공사향물질(SMCs) 3종의 생물분해 특성을 조사한 결과 다음과 같은 결론을 얻을 수 있었다. 생물활성탄(BAC) 공정에서 인공사향물질 3종의 제거는 EBCT와 수온에 따라 큰 영향을 받으며, EBCT와 수온이 증가할수록 제거능이 증가하였다. 물질에 따른 제거능은 MK가 가장 높았고 다음으로 HHCB, AHTN 순이었다. 또한, 활성탄 재질에 따른 생물활성탄(BAC) 및 안트라사이트 biofilter에서의 인공사향물질 3종의 제거는 석탄계 재질의 BAC에서 생물분해능이 가장 높았고, 다음으로 목탄계, 야자계, 안트라사이트 순으로 조사되었다. 인공사향물질 3종에 대한 생물분해 속도상수($K_{biodeg}$)와 반감기($t_{1/2}$)는 수온이 $5{\sim}25^{\circ}C$일 때 0.0082~0.4452 $min^{-1}$와 1.56~84.51 min이었으며, 수온이 $15^{\circ}C$와 $25^{\circ}C$로 증가시켰을 때 $5^{\circ}C$에서의 반감기보다 3.1~9.3배 감소되었다.

• 약학회지
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• 제34권2호
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• pp.126-132
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• 1990

To enhance the activity of ibuprofen, amides of ibuprofen, 1-piperazinyl-2-(4-isobutylphenyl)propionamide(Ibu-P.A.) and 1-(4-methylpiperazinyl)-2-(4-isobutylphenyl)propionamide (Ibu-M.P.), were synthesized and the pharmaceutical properties and the pharmacological activities of the amides were studied. The lipid:water partition coefficients and pKa values were examined in vitro, and the antiinflammatory effect, analgesic effects, acute toxicity, and intestinal absorption were studied for the amides and compared with ibuprofen in vivo. The results are summarized as belows; 1) The lipid:water partition coefficients of Ibu-M.P. were higher than those of ibuprofen. 2) The calculated pKa values of ibuprofen and Ibu-M.P. were 5.49 and 8.66, respectively. 3) The antiinflammatory effects of ibuprofen, Ibu-P.A., and Ibu-M.P. were same intensity, but the duration of the effects of Ibu-P.A. and Ibu-M.P. were longer than that of ibuprofen. 4) The analgesic effect of Ibu-M.P. was more potent than those of ibuprofen and Ibu-P.A. in the acetic acid-induced writhing test. 5) The $LD_{50}$ was 495 mg/kg for ibuprofen, 187 mg/kg for Ibu-M.P., and over 1250 mg/kg for Ibu-P.A.. 6) The absorption rate constants(k) and half-life($t_{1/2}$) were 0.74($hr^{-1}$) and 0.94(hr) for ibuprofen, and 0.72 ($hr^{-1}$) and 0.96 (hr) respectively for Ibu-M.P..

• 생명과학회지
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• 제26권3호
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• pp.376-386
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• 2016

에폽토시스에 의한 세포자멸사는 암세포에 대한 항암제 효능의 핵심적 기전이다. 항암제의 대표적인 두 종류로 알려진 DNA-손상 약제(DNA-damaging agents, DDAs)와 미세소관-손상 약제(microtubule-damaging agents, MDAs)가 암세포에 야기하는 초기 항암신호전달 기전은 다르지만, 최종적으로는 대부분 미토콘드리아 의존-에폽토시스를 통해 암세포를 사멸시킨다. 한편, DDAs에 의한 에폽토시스 유도에는 wild-type 종양억제 단백질 p53의 역할이 매우 중요하다. 그러나 인체 암의 약 50% 이상이 p53유전자의 돌연변이 때문에 종양억제 단백질로서의 p53 기능이 불활성화 되어 있다. 따라서 p53과 무관하게 에폽토시스를 유도할 수 있는 MDAs를 이용한 항암치료는 돌연변이 p53을 지닌 암세포에 대해 유리한 화학요법으로 이해된다. 최근 본 연구진은 인체 급성 백혈병 세포주인 Jurkat T 세포를 모델로 하여, MDAs (nocodazole, 17-α-estradiol, 혹은 2-methoxyestradiol)의 항암작용과 관련된 세포주기 정지 및 에폽토시스 유도 기전을 구명하였다. 그 결과, Jurkat T 세포를 MDAs로 처리할 경우, 유사분열방추사의 결함에 의한 세포주기(전중기, prometaphase) 정지, 장시간에 걸친 Cdk1의 활성화, 활성화된 Cdk1에 의한 에폽토시스 조절인자들(Bcl-2, Bcl-xL, Mcl-1 및 Bim)의 인산화, 이에 따른 Bak 활성화, 미토콘드리아막 손상 및 카스파아제 연쇄 활성화에 의해 에폽토시스가 유도됨을 밝혔다. 또한 동일한 MDA 처리 조건하에서 Bcl-2 혹은 Bcl-xL의 과발현시켜 에폽토시스 진행을 차단할 경우, Jurkat T 세포는 약제처리 후에 전중기 정지된 4N 상태에 도달하지만, 이어서 유사분열 불이행(mitotic slippage) 및 내재복제(endoreduplication)가 진행되어 다배수체들(polyploids; 8N, 16N)을 생성하게 됨을 확인하였다. 이러한 결과는 MDAs처리에 따른 다배수체들의 생성을 차단하는 세포 내 기전으로서, 전중기 정지된 4N 세포의 에폽토시스에 의한 제거가 매우 중요함을 보여준다. 특히, 다배수체는 유전적으로 매우 불안정하여 암세포의 항암제 내성 획득 및 암 재발과 직접 연관되는 것으로 알려져 있으므로, 에폽토시스 기전에 결함이 있는 암세포를 대상으로 MDAs를 이용한 항암 화학요법을 시행할 경우에는 다배수체 세포의 생성을 차단하기 위한 새로운 수단이 반드시 병행되어야 할 것으로 사료된다.

• Biomolecules & Therapeutics
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• 제17권2호
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• pp.205-210
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• 2009

The present study investigated the effects of hydrocortisone on the pharmacokinetics of loratadine in rats after intravenous and oral administration. A single dose of loratadine was administered either orally (4 mg/kg) or intravenously (1 mg/kg) with or without oral hydrocortisone (0.3 or 1.0 mg/kg). Compared to the control group (without hydrocortisone), after oral administration of loratadine, the area under the plasma concentration-time curve (AUC) was significantly increased by 30.2-81.7% in the presence of hydrocortisone (p<0.05). The peak plasma concentration ($C_{max}$) was significantly increased by 68.4% in the presence of 1.0 mg/kg hydrocortisone after oral administration of loratadine (p<0.05). Hydrocortisone (1.0 mg/kg) significantly increased the terminal plasma half-life ($t_{1/2}$) of loratadine by 20.8% (p<0.05). Consequently, the relative bioavailability of loratadine was increased by 1.30- to 1.82-fold. In contrast, oral hydrocortisone had no effects on any pharmacokinetic parameters of loratadine given intravenously. This suggests that hydrocortisone may improve the oral bioavailability of loratadine by reducing first-pass metabolism of loratadine, most likely mediated by P-gp and/or CYP3A4 in the intestine and/or liver. In conclusion, hydrocortisone significantly enhanced the bioavailability of orally administered loratadine in rats, which may have been due to inhibition of both CYP 3A4-mediated metabolism and P-gp in the intestine and/or liver by the presence of hydrocortisone.

• 한국환경농학회지
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• 제25권4호
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• pp.359-364
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• 2006

Reversed-phase high-performance liquid chromatography (HPLC) techniques were developed to quantify abamectin (ABM) in paprika (Capsicum annum). Separation was achieved on a $C_{18}$ ODS column with a mobile phase of acetonitrile/water (96/4, v/v) mixture in an isocratic elution at the flow tate of 1.2 mL/min for avermectins (AVMs). The retention times were 8.0 and 9.7mins for AVM $B_{lb}$ and AVM $B_{1a}$, respectively. Residual AVMs (sum of AVM $B_{1a}$, AVM $B_{1b}$ and 8,9-Z-AVM $B_{1a}$) in the vegetable were extracted with acetonitrile, and the silica solid-phase extraction cartridges were used to purify the extract. AVMs were derivatized using trifluoroacetic acid and 1-methylimidazole, and the derivatives were determined with a fluorescence detector (excitation at 365 nm and emission at 470 nm). High and consistent recoveries, ranging from 93% to 115%, were obtained for AVM $B_{1a}$ and 8, 9-Z-AVM $B_{1a}$ at fortified levels of $20{\mu}g/kg\;and\;200{\mu}g/kg$ for paprika. The limit of quantitation (LOQ) was $2{\mu}g/kg$. The residual levels of AVMs in paprika in a field experiment from one day to seven days after the last application decreased from 18.40 to $7.59{\mu}g/kg$. The half-life $(T_{1/2})$ of AVMs in paprika was 1.47 days.

• 대한영양사협회학술지
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• 제5권1호
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• pp.1-9
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• 1999

This study was aimed to implement and evaluate worksite nutrition counseling for industrial workers with hyperlipidemia in Kyung-buk area. Forty-six subjects consisted of 41 men and 5 women who were diagnosed hyperlipidemia though health examination had their average age, 40.3$\pm$ 6.0 and half of them were office workers and one third labor workers. Twenty-eight subjects had fatty liver with or without other complications and six had gastric problems. The subjects were interviewed using questionnaires on food habit, food frequency, smoking, drinking and exercise, and they were given nutrition counseling which was continued for 7 months. Desirable food selections were practiced using foods or food models and various written materials individually or as group during lunch times and breaks. After counseling, smoking and drinking were reduced and exercise and food habits were improved. Average levels of initial serum total cholesterol(T-Chol), HDL-cholesterol(HDL-Chol) and triglyceride(TG) were 214$\pm$ 44, 45.07$\pm$ 7.14 and 281$\pm$ 13mg/dl respectively and were not changed significantly except 2.30$\pm$ 7.04mg/dl increase of HDL-Chol(p<0.1) after nutrition counseling. However, subjects who improved their food habits and smoking, drinking and exercise habits had higher tendency to have reduced serum T-Chol and TG levels compared with those who drank less. Food habit score was negatively correlated with serum TG levels(r=-0.378, p<0.01). It is concluded that an efficient and regular nutrition counseling by dietitian at worksite is beneficial for health of industrial workers.

• 한국임상수의학회지
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• 제36권3호
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• pp.159-165
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• 2019

Pimobendan is an inodilator used to treat canine heart failure, and pentoxifylline is reported to be beneficial for microcirculation and heart disease. The purpose of this study was to evaluate the pharmacokinetic and pharmacodynamic profiles of a novel pimobendan-pentoxifylline liquid mixture after oral administration to dogs. Eight healthy Beagle dogs were included in the study. The dogs were divided into the control group (orally administered water; n = 4) and experimental group (orally administered pimobendan-pentoxifylline liquid mixture [pimobendan 0.25 mg/kg, pentoxifylline 15 mg/kg]; n = 4). Plasma samples were obtained and echocardiographic indices were measured for 24 hours after administration. The concentrations of pimobendan and pentoxifylline were quantified by using a liquid chromatography-mass spectrometer (LC-MS). The elimination half-life ($T_{1/2}$) was $32.96{\pm}9.80mins$ for pimobendan and $29.49{\pm}6.67mins$ for pentoxifylline. The time to reach maximum concentration ($T_{max}$) were $52.50{\pm}31.22mins$ for pimobendan and $41.25{\pm}18.87mins$ for pentoxifylline. The maximum blood concentration ($C_{max}$) was $96.92{\pm}75.64ng/mL$ for pimobendan and $7074.07{\pm}3261.1ng/mL$ for pentoxifylline. Of the echocardiographic indices, fractional shortening (FS) and left ventricular internal diameter at end systole (LVIDs) were significantly altered at 1-3 hours after the administration of pimobendan-pentoxifylline liquid mixture. The pimobendan-pentoxifylline liquid mixture was well tolerated by the dogs, with no adverse effects observed during the study.

• 원예과학기술지
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• 제32권5호
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• pp.666-672
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• 2014

본 연구는 저온 저장된 키위과실의 상온 유통 중 에틸렌 발생 및 품질에 미치는 영향을 확인함으로써 유통기간 연장에 NO 처리 효과를 확인하기 위해서 수행하였다. 1개월 저장된 키위를 $200{\mu}L{\cdot}L^{-1}$ NO를 처리한 후 대조구와 함께 상온에 저장하면서 품질을 비교하였다. 상온에서 저장하는 동안 무게손실은 무처리구에 높았다. 에틸렌 생성은 NO 처리에 의해서 2일 지연되었으며, 호흡률은 대조구에 비해 2배이상 낮았다. 3개월 저장된 키위과실은 100, 200, 그리고 $500{\mu}L{\cdot}L^{-1}$ 농도로 NO를 처리하였다. 대조구는 NO를 처리하지 않은 무처리구와 $N_2$ 처리구를 두었다. 무게손실은 $100{\mu}L{\cdot}L^{-1}$에서 가장 많았으며, 1개월 저장된 과실에 비해서도 높은 손실률을 보였다. 에틸렌 생생은 대조구와 $100{\mu}L{\cdot}L^{-1}$ NO에서 높은 반면 $200{\mu}L{\cdot}L^{-1}$ NO와 $500{\mu}L{\cdot}L^{-1}$ NO에서는 상대적으로 낮았다. 경도는 무처리구와 $N_2$ 처리구는 저장일수가 경과 되면서 급격히 연화된 반면, NO 처리구에서는 6일까지 경도가 높게 유지되었으며, 특히 $200{\mu}L{\cdot}L^{-1}$ NO 처리구는 9일까지 유지되었다. 키위과실로부터 채취하여 배양된 Botrytis cinerea에 NO를 처리한 결과 처리 후 2일 경과될 때까지 무처리구와 $N_2$ 처리구에 비해서 NO 처리구는 곰팡이 번식이 적었다. 이상의 결과를 종합해 보면 저장된 과실을 상온에 유통하기 전에 NO 처리는 에틸렌 발생 및 호흡을 저지시키고, 연화를 지연시키는데 효과가 있다. NO의 적정 처리 농도는 $200{\mu}L{\cdot}L^{-1}$ NO을 기준으로 너무 낮거나 높으면 NO의 효과가 줄어든다.

• 약학회지
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• 제54권4호
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• pp.252-257
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• 2010

The aim of this study was to investigate the effect of resveratrol on the pharmacokinetics of nifedipine in rats. The pharmacokinetic parameters of nifedipine were measured after the oral administration of nifenipine (6 mg/kg) in the presence or absence of resveratrol (0.5, 2.5 and 10 mg/kg, respectively). The effect of resveratrol on the P-glycoprotein (Pgp), CYP 3A4 activity was also evaluated. Resveratrol inhibited CYP3A4 enzyme activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of 0.94 ${\mu}M$. In addition, resveratrol significantly enhanced the cellular accumulation of rhodamine 123 in MCF-7/ADR cells overexpressing P-gp. Compared to the control groups, the presence of 2.5 mg/kg and 10 mg/kg of resveratrol significantly (p<0.05, p<0.01) increased the area under the plasma concentrationtime curve (AUC) of nifedipine by 49~75%, and the peak concentration ($C_{max}$) of nifedipine by 48~66%. The absolute bioavailability (AB%) of nifedipine was significantly (p<0.05) increased by 22.9-34.8% compared to the control (19.8%). The terminal half-life ($T_{1/2}$) of nifedipine was significantly (p<0.05) increased compared to the control. While there was no significant change in the time to reach the peak plasma concentration ($T_{max}$) of nifedipine in the presence of resveratrol. It might be suggested that resveratrol altered disposition of nifedipine by inhibition of both the CYP3A and P-glycoprotein efflux pump in the small intestine of rats. In conclusion, the presence of resveratrol significantly enhanced the oral bioavailability of nifedipine, suggesting that concurrent use of resveratrol or resveratrol-containing dietary supplenment with nifedipine should require close monitoring for potential drug interation.

• Journal of Pharmaceutical Investigation
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• 제38권3호
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• pp.151-155
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• 2008

Circadian variations of acebutolol and its main metabolite, diacetolol pharmacokinetics were studied after a single oral administration of acebutolol (10 mg/kg) to eight rabbits at 10 : 00 AM (in the morning) and 10 : 00 PM (at night). The plasma concentration profiles of acebutolol were significantly different (P<0.05) between 10 : 00 AM and 22 : 00 PM, suggesting circadian variations of pharmacokinetic behaviors. A significant circadian rhythm of pharmacokinetic parameters was noted in rabbits, showing higher total body clearance (CL/F), and lower the area under the plasma concentration-time curves (AUC) of acebutolol than that at night. The half-life ($t_{1/2}$) of acebutolol and diacetolol were also significantly shorter in the morning than at night (P<0.05). Metabolite-parent AUC ratio at night significantly decreased compared to in the morning, implying that night time could inhibit acebutolol metabolism than in the morning. From this study there was an administration-time difference of acebutolol pharmacokinetics in the rabbits. The optimized dosing regimen of acebutolol can be decided by considering circadian rhythm so that the effective therapies are established for patients.