• 대한한방부인과학회지
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• 제15권4호
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• pp.45-60
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• 2002

생쥐의 calvarial osteoblast세포를 분리배양하여 gelatinase생성여부를 골흡수과정에서의 역할을 규명하기 위하여 SDS-PAGE-zymography분석을 한 결과 progelatinase-A를 항속적으로 합성하고 있음을 확인하였다. 생쥐의 osteoblasts를 골재흡수 약물인 PTH, $1,25(OH)_2D_3$, 단핵구배양액 (MCM) 그리고 IL-1으로 자극시키면 gelatinase생산을 촉진하여 콜라겐분해가 증가되었으나, indomethacin과 dexamethasone은 생쥐의 osteoblastic세포의 collagenolysis를 저해하였다. 한편, 골재흡수에 IL-1을 생쥐태아 유래의 장골조직배양 (fetal mouse long bone organ culture)에 처리하자 IL-1 은 골재흡수를 촉진하였다. 더우기, $IL-1{\alpha}$의 농도의존성에 대한 indomethacin과 dexametasone의 영향을 검토한 결과 직선형의 비례커브로 영향을 미쳤다. 이러한 골대사의 지견을 바탕으로 대영전-자하거의 열수추출물의 시험관내 독성검사에서 $1-200\;{\mu}g/ml$의 농도에서는 독성이 없었으며, 또한, $300\;{\mu}g/ml$ 농도에서도 생쥐의 calvarial골에는 독성이 없었다. 대영전-자하거 extract는 PTH (2 units/ml), MCM (5%, v/v), $rhIL-1{\alpha}$ (1 ng/ml) $1,25(OH)_2D_3$ (10 ng/ml)처리에 대해서 그리고 $IL-1{\alpha}$와 $IL-1{\beta}$-유발 collagenolysis에 대해서도 보호효과가 있었다. 대영전-자하거extract을 1시간동안 전처리와 후처리에서 콜라겐분해에 약간의 보호활성이 있었으며 $IL-1{\alpha}$와 $IL-1{\beta}$에 의해 유발되는 콜라겐분해에 보호활성이 보였다. 1시간동안 전처리는 콜라겐분해를 감소시키며, 대영전-자하거 extract는 gelatinase효소를 저해하였으며 PTH, $1,25(OH)_2D_3$, $IL-1{\beta}$ 및 $IL-1{\alpha}$로 유발된 효소활성화가 저해되었다. 즉, 대영전-자하거 extracts는 $IL-1{\alpha}-$와 $IL-1{\beta}$에 의해 촉진되는 골재흡수에 효과적이었으며, 비스테로이드성 항염증제제 (indomethacin 과 dexamethasone)에 의한 골재흡수방지 효과와 유사하였다. 이러한 결과는 대영전-자하거extract가 골다공증치료에 효과적임을 나타내는 것이다.

• 약학회지
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• 제37권3호
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• pp.235-242
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• 1993

8-Fluorociprofloxacin(8-FCP) is an investigational quinolone derivative that is substituted with fluorine at the C-8 position of ciprofloxacin(CP). It was found that the in vitro activity of 8-FCP against Gram(+) bacteria was more potent that of CP, but the opposite against Gram(-) bacteria was true. However, 8-FCP showed better in vivo efficacy than CP against representative Gram(-) organisms, E. coli and K pneumoniae. In an attempt to seek for factors causing this discrepancy in the antibacterial activities, a comparative pharmacokinetic study of 8-FCP and CP was conducted in mice and rats treated either intravenously or orally at a single dose of 30 mg/kg. The pharmacokinetic parameters in mice were as follows; the mean peak serum concentrations(C$_{max}$) following i.v. and oral doses were 12.4 and 5.3 $\mu\textrm{g}$/ml for 8-FCP, and 9.5 and 2.5 $\mu\textrm{g}$/ml for CP, respectively. The terminal half-life(t$_{1/2\beta}$) was 72.9 min for 8-FCP, and 98.2 min for CP, and the oral bioavailability(F) was 89.9% for 8-FCP, and 50.5% for CP. In rats, the mean ($\pm$SD) $C_{max}$ after i.v. administration were 11.6$\pm$1.6 $\mu\textrm{g}$/ml for 8-FCP, and 10.2$\pm$1.3 $\mu\textrm{g}$/ml for CP, whereas oral administration produced $C_{max}$ of 5.9$\pm$1.8 $\mu\textrm{g}$/ml for 8-FCP and 1.1$\pm$0.9 $\mu\textrm{g}$/ml for CP, respectively. The t$_{1/2\beta}$ was 67.9$\pm$8.4 min for 8-FCP, and 76.4$\pm$7.2 min for CP. The F was 88.6$\pm$6.3% for 8-FCP, and 40.7$\pm$6.5% for CP. Marked differences were observed between the two quinolones in the $C_{max}$ and the area under the concentration-time curve obtained after oral administration in mice and rats. The extent of 8-FCP absorption in both mice and rats was approximately 2-fold higher than that of CP, suggesting that the fluorine atom attached to C-8 plays an important role in facilitating oral absorption from the gastrointestinal tract.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.973-977
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• 2002

The pharmacokinetic of paclitaxel (1 mg/kg, i.v.) was investigated in rabbits with carbon tetrachloride-induced hepatic failure. The area under the plasma concentration-time curve (AUC) of paclitaxel was significantly (p<0.01) increased in severe carbon tetrachloride-induced hepatic failure rabbits ($1364.54{\pm}382.07$ ng/ml$\cdot$hr) compared to that of normal rabbits ($567.52{\pm}141.88$ ng/ml$\cdot$hr), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($803.1{\pm}208.81$ ng/ml$\cdot$hr). The volume of distribution (Vd) (6.25$\pm$1.56 L) and the elimination rate constant($\beta$) ($0.09{\pm}0.025{\;}hr^{-1}$) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits were significantly (p<0.05) decreased compared to those of normal rabbits ($11.65<{\pm}2.91$L, $0.12{\pm}0.030{\;}hr^{-1}$), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($9.46{\pm}2.37$ L, $0.10{\pm}0.026{\;}hr^{-1}$). Total body clearance ($CL_t$) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits ($0.733{\pm}0.183$ L/hr/kg) was significantly (p<0.01) decreased compared to that of normal rabbits ($1.762{\pm}0.440$ L/hr/kg), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($1.245{\pm}0.311$ L/hr/kg). The half-life(t1/2) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits ($7.71{\pm}2.16$ hr) was significantly (p<0.05) increased compared to that of normal rabbits ($5.75{\pm}1.44$hr), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($6.77{\pm}1.76$hr). This results could be due to inhibition of paclitaxel metabolism in liver disorder rabbits since paclitaxel is essentially metabolized in liver. The findings suggest that the dosage regimen of paclitaxel should be adjusted when the drug would be administered in patients with liver disorder in a clinical situation.

• Asian-Australasian Journal of Animal Sciences
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• 제16권6호
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• pp.806-812
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• 2003

Attempts have been made to establish relationship between the response to ACTH challenge in female calves, growth and first lactation performance. A total of 19 Holstein calves weighing 100 kg i. v. were given 0.50 IU of ACTH/kg $BW^{.75}$ (EXACTHIN inj., Richter G., Budapest) at 60 days of age. Serial blood samples were taken at times 0, 0.5, 1, 2, 3, 4 and 5 hours and analyzed for cortisol, glucose insulin and FFA levels. From challenge series the area under the curve from time of administration and the following 5 h were calculated. Negative, and mostly loose relationship between response to ACTH challenge for cortisol, insulin, or FFA and ADWG during growth have been established (p>0.05) with positive one for glucose. Bivariate coefficients of correlation varied within the range from -0.35 to 0.15. Estimations reveal negative correlation between the length of first lactation and cortisol or insulin (r=-0.80, p<0.001 and r=-0.45, p<0.10, resp.) Close association between cortisol or insulin and actual first lactation milk yield was found (r=-0.48, p<0.10; r=-0.64, p<0.01, resp.). Close relationship between the response to ACTH challenge and milk protein yield was present only for insulin (r=-0.59, p<0.05).

• Ocean and Polar Research
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• 제41권4호
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• pp.233-250
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• 2019

A re-assessment of the age structure of the population of the Antarctic icefish Pseudochaenichthys georgianus based on body length data covering the years 1976-2009 and including larvae and postlarvae collected in 1989 and 1990 allowed us to define age groups 0, I, and II as containing fish with respective body lengths of 6-9 cm, 15-27 cm and 27-39 cm. Age at maturity (first spawning) was found to occur in age group III at body lengths that have been falling from 50.1 cm in 1979 to 45.4 cm in 1992. Considering postlarvae together with adult fish, the v. Bertalanffy growth curve parameters were determined as L_∞ = 60.62 cm, k = 0.4, t₀ = 0.25. Although the reasons for a maturity at shorter body lengths is not fully understood a host of environmental factors like increasing water temperatures and possibly changes in currents, interspecific competition, food availability, etc. are likely to be involved. Global warming (and not primarily overfishing) is likely to have been responsible for the disappearance of larger fish in the surface waters of South Georgia since 1977, for virtually all commercial fishing stopped in the early 1990s. On the other hand, the appearance of numerous younger spawning individuals suggests that larvae do survive in the colder deeper water below 200 m. The biomass of Ps. georgianus oscillates with a 4-year periodicity in contrast to that of the coexisting icefish Chaenocephalus aceratus: the former with a lower biomass in warm years and a higher one in cold years. The biomass of the third species of icefish in the region, i.e. Champsocephalus gunnari, also oscillates, but with a longer periodicity than that involved in the biology of the other two and its biomass increases in contrast to the other two species. The result is that the biomass all three species considered together is rather stable.

• Journal of Astronomy and Space Sciences
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• 제10권2호
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• pp.123-145
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• 1993

충북대학교 천문우주학과의 UBVRI 측광기가 부착된 20 cm 망원경을 이용하여 1988년 12월부터 1991년 3월 사이의 33일밤 동안 Algol을 광전측광 관측하여 총 3465점의 관측값을 얻었다. 이 관측값을 이용하여 UBVRI 광도곡선을 만들었고 5개의 극심시각 JDHel 2447898.0938, JDHel 2447908.1014, JDHel 2448265.1205, JDHel 2448288.0598, JDHel 2448275.146 을 결정하였다. 우리가 얻은 UBVRI 광도곡선을 동시에 Wilson-Devinney 방법으로 분석하여 측광학적 해를 구했다. 이 해로 부터 얻은 i= $82.{\circ}47$, q=0.227, $r_1$=0.2102, $r_2$=0.2512와 Hill et al.(1971)의 분광학적 해의 인수들을 이용하여 Algol A,B,C, 각각에 대한 질량에 반경을 $m_1$=3.36, $m_2$=0.76, $m_3$=1.6, $R_1$=2.97, $R_2$=0.76과 같이 구했다. 여기서 사용한 단위는 태양질량 단위와 태양반경 단위이다. 이러한 우리의 결과들은 Kim(1989)이 보고한 값들과 대체로 비슷하다. 우리의 해로 부터 은 5색의 $l_1$, $l_2$, $l_3$ 값들을 Planck 곡선에 fitting 시키는 방법에 의해 Algol C의 온도를 $T_3$=8800로, 그리고 $R_3$=$1.6R_\odot$을 유도했다. Algol A와 B의 배치 형태가 준접촉형인 것은 case B 질량 이동에 의해 생긴 결과로 믿어지며, 질량-반경동에 나타난 이들의 위치에 의하면 Algol B는 수소연소 단계에서도 상당히 진화된 상태에 있는 것으로 추정된다.로 추정된다.

• Archives of Pharmacal Research
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• 제26권7호
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• pp.564-568
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• 2003

Pharmacokinetic and pharmacodynamic properties of gliclazide were studied after an oral administration of gliclazide tablets in healthy volunteers. After an overnight fasting, gliclazide tablet was orally administered to 11 volunteers; Additional 10 volunteers were used as a control group (i.e., no gliclazide administration). Blood samples were collected, and the concentration determined for gliclazide and glucose up to 24 after the administration. Standard pharmacokinetic analysis was carried out for gliclazide. Pharmacodynamic activity of the drug was expressed by increase of glucose concentration ($\Delta$PG), by area under the increase of glucose concentration-time curve ($AUC_{$\Delta$PG}$) or by the difference in increase of glucose concentration ($D_{$\Delta$PG}$) at each time between groups with and without gliclazide administration. Pharmacokinetic analysis revealed that $C_{max}, T_{max}$, CL/F (apparent clearance), V/F (apparent volume of distribution) and half-life of gliclazide were $4.69\pm1.38 mg/L, 3.45\pm1.11 h, 1.26\pm0.35 L/h, 17.78\pm5.27 L, and 9.99\pm2.15 h$, respectively. When compared with the no drug administration group, gliclazide decreased significantly the $AUC_{$\Delta$PG}$ s at 1, 1.5, 2, 2.5, 3 and 4 h (p＜0.05). The $\Delta$PGs were positively correlated with $AUC_{gliclazide}$ at 1 and 1.5 h (p＜0.05), and the correlation coefficient was maximum at 1 h (r = 0.642) and gradually decreased at 4 h after the administration. The $AUC_{$\Delta$PG}$s were positively correlated with $AUC_{gliclazide}$ at 1, 2, 3 and 4 h (p＜0.05), and the maximum correlation coefficient was obtained at 2 h (r=0.642) after the administration. The $D_{$\Delta$PG}$ reached the maximum at 1 h, remained constant from 1 h to 3 h, and decreased afterwards. Therefore, these observations indicated that maximum hypoglycemic effect of gliclazide was reached at approximately at 1.5 h after the administration and the effect decreased, probably because of the homeostasis mechanism, in health volunteers.

• Archives of Pharmacal Research
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• 제22권1호
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• pp.60-67
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• 1999

The object of this work was to study the pharmacokinetic differences and the cause of these differences in cirrhotic rats induced by biliary obstruction when aminophylline (8 mg/kg as theophylline, i.v.) was administered. The concentrations of theophylline and its major metabolite (1,3-dimethyluric acid) in plasma were determined by HPLC. In addition, formation of 1,3-dimethyluric acid from theophylline in microsomes and the changes in the activity of drug metabolizing enzymes, which are suggested to be involved in theophylline metabolism, were determined. In cirrhotic rats, the systemic clearance of theophylline was reduced to 30% of the control value while AUC (area under the palsma concentration-tie curve) and (t1/2)$\beta$ were increased 1.3 fold and3.5 fold, respectively. The formation of 1,3-dimethyluric acid was decreased to 30% of the control value in microsomes of cirrhotic rat liver. In cirrhotic rat liver, activities of aniline hydroxylase (CYP2E1 related), erythromycin-N-demethylase (CYP3A related), and methoxyresorufin-O-demethylase (CYP1A2 related), which were reported to be related with theophyline metabolism, were decreased to 67%, 53%, and 76% that of normal rat liver, respectively. From the results, it can be concluded that in cirrhotic rats induced by biliary obstruction, the total body clearance of theophylline is markedly reduced and it may be due to decreased activity of drug metabolizing enzymes in liver.

• Nuclear Engineering and Technology
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• 제4권3호
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• pp.214-222
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• 1972

광학급 LiF단결정의 열형광유선은 r선조사선양이 증가함에 따라서 변화한다. 즉 선량이 적을 때는 2개의 glow peak를 가지나, 선양이 정차 증가하여 10$_{5}$ rontgen 정도에 이르면 5개의 glow peak를 나타낸다. 이들 glow peak에 대응하는 energy 준위 Ei(i=1,2,3,4, 및 5)는 전도대 밑으로 부터의 깊이로 표시할 때 다음과 같은 값을 갖는다. 이들 E$_i{$의 값은 가열속도 $\theta_1$=6.6$^{\circ}C$/sec와 $\theta_2$=3.4$^{\circ}C$/sec에 대한 glow peak의 온도를 얻은 다음, Randall-Wilkins의 이론에 따라서 계산되었다. 광학급 LiF단결정에서 E$_1$과 E$_2$이외의 전자 trap은 열적으로 불안정하며 LiF(Mg) 열형광선양계에 불가결한 것으로 되어있는 sensitization의 효과가 거의 없다. LiF(Mg)는 $\theta$=6.6$^{\circ}C$/sec 일때, 17$0^{\circ}C$와 23$0^{\circ}C$에 glow peak를 나타내며 이들에 대응하는 전자 trap E$_4$와 E$_{5}$ 이외에 방사선이 조사됨에 따라서 E$_1$, E$_2$, E$_3$ 및 E$_{6}$의 전자 trap이 형성되며 이들 값은 다음과 같다. LiF(Mg)에서 방사선상해 때문에 형성된 E$_1$, E$_2$, E$_3$및 E$_{6}$는 모두 상당히 열적으로 안정하며, sensitization과정에서 형성된다. 이 안정한 6준위계에서 LiF(Mg)예 의한 방사선 선양측정이 시행되어야 한다. E$_1$,E$_2$,E$_3$ 및 E$_{6}$의 안정성은 LiF결정내의 $Mg^{$ ++/ 불순물의 영향으로 사료된다. 광학급 LiF단결정의 열형광에서 r선양의 대수표시양과 전열형광양의 대수표시 사이에 비선형성을 나타낸다. 그러나 열적으로 안정한 12$0^{\circ}C$ glow peak만을 고려하여 r선양의 대수표시양과 12$0^{\circ}C$ slow peak의 높이의 대수표시량 사이에서 비선형성이 감소되어, LiF(Mg)에 대한 곡선과 매우 유사한 곡선을 얻게 된다.

• Biomolecules & Therapeutics
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• 제18권4호
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• pp.469-476
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• 2010

This study was to investigate the effect of apigenin on the bioavailability of paclitaxel after oral and intravenous administration in rats. The effect of apigenin on P-glycoprotein (P-gp), cytochrome P450 (CYP)3A4 activity was evaluated. The pharmacokinetic parameters of paclitaxel were determined in rats after oral (40 mg/kg) or intravenous (5 mg/kg) administration of paclitaxel with apigenin (0.4, 2 and 8 mg/kg) to rats. Apigenin inhibited CYP3A4 activity with 50% inhibition concentration ($IC_{50}$) of 1.8 ${\mu}M$. In addition, apigenin significantly inhibited P-gp activity. Compared to the control group, apigenin significantly increased the area under the plasma concentration-time curve (AUC, p<0.05 by 2 mg/kg, 59.0% higher; p<0.01 by 8 mg/kg, 87% higher) of oral paclitaxel. Apigenin also significantly (p<0.05 by 2 mg/kg, 37.2% higher; p<0.01 by 8 mg/kg, 59.3% higher) increased the peak plasma concentration ($C_{max}$) of oral paclitaxel. Apigenin significantly increased the terminal half-life ($t_{1/2}$, p<0.05 by 8 mg/kg, 34.5%) of oral paclitaxel. Consequently, the absolute bioavailability (A.B.) of paclitaxel was significantly (p<0.05 by 2 mg/kg, p<0.01 by 8 mg/kg) increased by apigenin compared to that in the control group, and the relative bioavailability (R.B.) of oral paclitaxel was increased by 1.14- to 1.87-fold. The pharmacokinetics of intravenous paclitaxel were not affected by the concurrent use of apigenin in contrast to the oral administration of paclitaxel. Accordingly, the enhanced oral bioavailability by apigenin may be mainly due to increased intestinal absorption caused via P-gp inhibition by apigenin rather than to reduced renal and hepatic elimination of paclitaxel. The increase in the oral bioavailability might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced first-pass metabolism of paclitaxel via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by apigenin. It appears that the development of oral paclitaxel preparations as a combination therapy is possible, which will be more convenient than the i.v. dosage form.