• Journal of Embryo Transfer
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• v.20 no.3
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• pp.297-302
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• 2005

Artificial insemination (AI) technology has widely applied in domestic animals including cattle for production and preservation of valuable animals. However, AI in goat was poorly studied. We here compared two different estrus synchronization methods, CIDR (controlled intravaginal drug release)+$PGF_2a$ and CIDR+PMSG, in Korean native goats. After treatment of CIDR+$PGF_2a$ or CIDR+PMSG for estrus synchronization, AI was applied to 38 recipients. Of 18 recipients treated with CIDR+$PGF_2a$, 4 recipients produced offsprings. However, no pregnancy was obtained in 20 recipients treated with CIDR+PMSG. Especially, after treatment of CIDR+$PGF_2a$, AI with fresh or frozen sperm showed markedly higher parturition rates than that of CIDR+PMSG. From these results, we suggest that combination of CIDR and $PGF_2a$ could be used as good method for estrus synchronization in Korean native goats.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.227-237
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• 1995

Omeprazole(OMP) complexes such as inclusion complexes of OMP with $hydroxypropyl-{\beta}-cyclodextrin$(HPCD) and ${\beta}-cyclodextrin({\beta}-CD)$, OMP-cholestyramine(CHL) and OMP-ethylenediamine(OMP-ED) were prepared, respectively. The partition coefficients in Witepsol H-15 /pH 7.4 phosphate buffer solution of OMP complexes$(OMP-HPCD;\;3.69{\pm}0.26,\;OMP-{\beta}-CD;\;4.08{\pm}0.21,\;OMP-CHL;\;4.36{\pm}0.25\;and\;omeprazole\;sodium(OMP-Na);\;3.64{\pm}0.37)$ were higher than that of OMP $(2.66{\pm}0.47)$. OMP was not completely dissolved until even 3 hrs, but all the OMP complexes studied were released about 100% in 20 min. The rectal suppositories containing OMP or each above OMP complex were prepared using Witepsol H-15 base, and their dissolution and stability were examined, and pharmacokinetic study were investigated after their rectal administrations to the rabbits. While the suppository containing OMP was released only less than 60% in 150 min, $OMP-{\beta}-CD$, OMP-CHL, OMP-Na and OMP-ED suppositories were all released about 65% in 20 min. Especially, OMP-HPCD suppository released OMP about 70% in 10 min. All the additives such as sodium laurylsulfate, eglumine, arginine and PVP increased drug release from OMP-HPCD suppository to some extent. The decomposition rate constants of OMP in the suppositories were $9.117{\times}10^{-3}\;day^{-l}$ for OMP suppository, $2.121{\times}10^{-2}$ for OMP-HPCD, $1.607{\times}10^{-2}$ for $OMP-{\beta}-CD$, $9.26{\times}10^{-3}$ for OMP-Na, $6.769{\times}10^{-3}$ for OMP-CHL and $5.58{\times}10^{-3}\;day^{-l}$ for OMP-ED suppository, respectively. Additives such as arginine, eglumine and ED had some stabilizing effect for OMP-HPCD, OMP-CHL and OMP-Na suppositories, respectively. After 6 month-storage at $30^{\circ}C$, 75% RH, OMP-CHL suppository was most stable. The values of Tmax for OMP-HPCD and OMP-Na suppositories were $11.7{\pm}2.36\;and\;11.4{\pm}2.56\;min$, respectively. The values of Cmax for OMP-HPCD and OMP-CHL suppository were $2.31\;{\mu}g/ml\;(p<0.01)\;and\;1.89\;{\mu}g/ml\;p<0.01)$, respectively. The values of AUC for OMP and $OMP-{\beta}-CD$ suppository were $61.9{\pm}25.79\;and\;68.6{\pm}29.48\;{\mu}g\;{\cdot}\;min/ml$, and the corresponding values for OMP-HPCD and OMP-CHL were $106.1{\pm}43.16\;(p<0.05)\;and\;127.3{\pm}42.52\;{\mu}g\;{\cdot}\;min/ml(p<0.01)$, respectively. The above results indicate the OMP-HPCD and OMP-CHL suppositories have the excellent bioavailabilties in vivo study.

• Journal of Embryo Transfer
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• v.24 no.1
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• pp.47-55
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• 2009

This study was performed to investigate the possibility of repeated superovulation treatment at interval from 27 days to 41 days in Hanwoo cattle and to compare with superovulation effect between doses of FSH 200 mg and FSH 400 mg. Different doses of FSH (200 mg or 400 mg) were injected at Day 8 after controlled internal drug release (CIDR) treatment for superovulation of Hanwoo donors following CIDR treatment (Day 8 after the estrus). Superovulation was repeated four times for one donor and number of corpus luteum (CL), number of embryos, number of transferable embryos and pregnancy rate after embryo transfer (ET) were investigated. 5 cows were used for each FSH treatment (10 cows in total). Average number of CL were $10.16{\pm}3.85$ and $11.56{\pm}2.35$ for the donors treated with FSH 200mg and FSH 400mg, respectively. Average number of embryos collected were $8.85{\pm}4.05$ and $8.30{\pm}1.73$ for the donors treated with FSH 200 mg and FSH 400 mg, respectively. Average number of transferable embryos were $5.48{\pm}2.45$ and $4.58{\pm}2.23$ for the donors treated with FSH 200 mg and FSH 400 mg, respectively. The pregnancy rate following ET with embryos collected from 200 mg FSH treated donors and 400 mg FSH treated donors were 61.9% and 53.8% respectively. The numbers of embryos tended to be decreased as the numbers of repeat of superovulation were elapsed. These results indicated that superovulation treatment by about a month to Hanwoo donors is usable and 200 mg of FSH is preferable for simple FSH treatment following CIDR treatment.

• Journal of Life Science
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• v.26 no.9
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• pp.1015-1021
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• 2016

5-fluorouracil (5-FU), a pyrimidine analog, is a widely used anticancer drug, which works through irreversible inhibition of thymidylate synthase. In the present study, it was investigated the anti-proliferative effects and molecular mechanisms of 5-FU using Ewing's Sarcoma CHP-100 Cells. The present data indicated that treatment of 5-FU to CHP-100 cells induced a G1 phase arrest of the cell cycle in a time-dependent manner. 5-FU-induced G1 arrest was correlated with the accumulation of the hypophosphorylated form of the retinoblastoma protein (pRB) and association of pRB with the transcription factors E2F-1 and E2F-4. Although 5-FU treatment did affect the levels of cyclin-dependent kinases, the levels of cyclin A and B were markedly down-regulated as compared with the untreated control group. In addition, 5-FU-induced G1 arrest of CHP-100 cells was also associated with the induction of apoptosis, as determined by apoptotic cell morphologies, degradation of poly(ADP-ribose) polymerase and Annexin V staining. Furthermore, 5-FU induced the loss of mitochondrial membrane potential with up-regulated pro-apoptotic Bax expression, down-regulated anti-apoptotic Bcl-2 expression and cytochrome c release from mitochondria to cytosol. Collectively, the data suggest that 5-FU is effective in inducing cell growth reduction and apoptosis, in part, by reducing phosphorylation of pRB and activating mitochondrial dysfunction in CHP-100 cells.

• Journal of Pharmacopuncture
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• v.7 no.1 s.12
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• pp.53-61
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• 2004

Substantial evidence suggests that behavioral and reinforcing effects of cocaine can be mediated by the mesolimbic dopaminergic system. It has been shown that repeated injections of cocaine produce increase in locomotor activity, expression of the immediate-early gene, c-fos in the nucleus accumbens (NAc), which was one of the main dopaminergic terminal areas. Herbal-acupuncture as a therapeutic intervention has been widely used for the treatment of many functional disorders such as drug abuse. Coptidis Rhizoma (CR) and its main component, berberine (BER) were selected as herbal medicine of herbal-acupuncture. Both medicines have been known to have the therapeutic effect on the central nervous system. In order to investigate the effects of CR and BER herbalacupuncture at shenmen (HT7) point (CR/H and BER/H) on the cocaine-induced behavioral sensitization, the influence of CR/H and BER/H on repeated cocaine-induced locomotor activity, the change of c-Fos expression in the brain by immunohistochemistry were examined. Male SD rats were given CR/H (0.4mg/kg) and BER/H (0.1mg/kg) 30 min before daily injections of cocaine hydrochloride (15mg/kg. i.p.) 10 days. After 3 days withdrawal, rats received a challenge injection of cocaine (15mg/kg, i.p.). Systemic challenge with cocaine produced much larger increased locomotor activity, accumbal Fos-like immunoreactivity in the NAc. Pretreatment with CR/H and BER/H significantly inhibited cocaine-induced locomotor activity, the change of c-Fos expression in the rats. Our data demonstrated that the inhibitory effects of cocaine-induced behavioral sensitization by CR/H and BER/H were closely associated with the reduction of presynaptic dopamine release in the NAc. These results suggest that CR/H and BER/H can be effectively applied to cocaine addiction.

• Journal of Pharmaceutical Investigation
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• v.34 no.2
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• pp.139-145
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• 2004

The purpose of the present study was to evaluate the bioequivalence of two risperidone tablets, Risperdal (Janssen Korea Co., Ltd.) and Rispen (Myung In Pharm. Co., Ltd), according to the guidelines of Korea Food and Drug Administration (KFDA). The risperidone release from the two risperidone formulations in vitro was tested using KP VIII Apparatus II method with various of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty four healthy male subjects, $23.33\;{\pm}2.10$ years in age and $69.24{\pm}8.05\;kg$ kg in body weight, were divided into two groups and a randomized $2\;{\times}\;2$ cross over study was employed. After one tablet containing 2 mg as risperidone was orally administered, blood was taken at predetermined time intervals and the concentrations of risperidone in serum were determined using HPLC method with UV detector. The dissolution profiles of two formulations were similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t$,$C_{max},\;and\;T_{max}$ were calculated and ANOVA test was utilized for the analysis of the parameters using logarithmically transformed $AUC_t$,$C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the Risperdal were 0.20, -1.29 and -11-09% for $AUC_t$,$C_{max},\;and\;T_{max}$, respectively There were no sequence effects two formulations in parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) (e.g.,$log(0.90){\sim}log(1.30)$ and $log(0.84){\sim}log(1.09)$ for$AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA guideline for the bioequivalence were satisfied, indicating Rispen tablet and Risperdal tablet were bioequivalent.

• Journal of Pharmaceutical Investigation
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• v.34 no.2
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• pp.147-153
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• 2004

The purpose of the present study was to evaluate the bioequivalence of two glimepiride tablets, $Amaryl^{\circledR}$ (Handok/Aventis Pharm. Co., Ltd.) and Glimed (Kuhn II Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The glimepiride release from the two glimepiride formulations in vitro was tested using KP VIII Apparatus II method with a variety of dissolution media (pH 1.2, 4.0, 6.8 buffer solution, water and blend of PSB 80 into each dissolution medium). Twenty six healthy male subjects, $22.65{\pm}2.19$ years in age and $66.55{\pm}8.85$ kg in body weight, were divided into two groups and a randomized $2\;{\times}\;2$ cross-over study was employed. After one tablet containing 2 mg as glimepiride was orally administered, blood was taken at predetermined time intervals and the concentrations of glimepiride in serum were determined using HPLC method with UV detector. The dissolution profiles of two formulations were similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the Amaryl were -3.70, -8.28 and 0.61% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) (e.g., $log(0.84){\sim}log(1.04)$ for $log(0.82){\sim}log(1.03)$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA guideline for the bioequivalence were satisfied, indicating Glimed tablet and Amaryl tablet were bioequivalent.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.3
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• pp.181-186
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• 2012

Fenofibrate is a selective peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) activator and is prescribed to treat hyperlipidemia. The mechanism through which $PPAR{\alpha}$ agonists reduce food intake, body weight, and adiposity remains unclear. One explanation for the reduction of food intake is that fenofibrate promotes fatty acid oxidation and increases the production of ketone bodies upon a standard experimental dose of the drug (100~300 mg/kg/day). We observed that low-dose treatment of fenofibrate (30 mg/kg/day), which does not cause significant changes in ketone body synthesis, reduced food intake in Long-Evans Tokushima (LETO) rats. LETO rats are the physiologically normal controls for Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are obese and cholecystokinin (CCK)-A receptor deficient. We hypothesized that the reduced food intake by fenofibrate-treated LETO rats may be associated with CCK production. To investigate the anorexic effects of fenofibrate in vivo and to determine whether CCK production may be involved, we examined the amount of food intake and CCK production. Fenofibrate-treated OLETF rats did not significantly change their food intake while LETO rats decreased their food intake. Treatment of fenofibrate increased CCK synthesis in the duodenal epithelial cells of both LETO and OLETF rats. The absence of a change in the food intake of OLETF rats, despite the increase in CCK production, may be explained by the absence of CCK-A receptors. Contrary to the OLETF rats, LETO rats, which have normal CCK receptors, presented a decrease in food intake and an increase in CCK production. These results suggest that reduced food intake by fenofibrate treatment may be associated with CCK production.

• Polymer(Korea)
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• v.28 no.3
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• pp.211-217
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• 2004

The sol to gel transition of aqueous solution of block copolymers consisting of methoxy poly (ethylene glycol) (MPEG) and biodegradable polyesters such as $\varepsilon$-caprolactone and L-lactide was investigated as a function of temperature. MPEG-PCL was prepared by ring opening polymerization of $\varepsilon$-caprolactone in the presence of HClㆍEt$_2$O as monomer activator at room temperature. Also, MPEG-PLLA was prepared by ring opening polymerization of L-lactide in the presence of stannous octoate at 115$^{\circ}C$. The properties of block copolymers were investigated by $^1$H-NMR, IR, and GPC as well as the observation of thermo sensitive phase transition in aqueous solution. As the hydrophobic block length increased, the sol to gel transition temperature increased and curve of that steepen to lower concentration. To confirm the gel formation at body temperature, we observed the formation of gel in the mice body after injection of 20 wt% aqueous solution of each block copolymer. After surging, we investigated the gelation in mice. The results obtained in this study confirmed the feasibility as biomaterials of injectable implantation for controlled release of drug and protein delivery.

• Journal of Veterinary Clinics
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• v.15 no.1
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• pp.131-139
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• 1998

Progesterone을 함유하고 있는 CIDR(Controlled Internal Drug Release)의 질내삽 입은 황체기를 인위적으로 연장시킬 수 있다. CIDR의 삽입이,삽입시 존재했던 우세난포 (dominant follicle)의 반응과 난포의 발육반응 그리고 2회 또는 3회의 난포주기를 가지고 있는 처려우에서 CIDR의 삽입기간동안 난포의 성장 및 발육에 어떠한 영향을 미치는가를 비교검 토하기 위하여 배란후 16일째의 처녀우 4마리에 7일동안 CIDR를 삽입하였다. CIDR의 삽입 은 발정의 발현을 억제시켰으며 그리고 발정주기의 길이를 정상 발정주기보다 유의성있게 연 장시켰다($26.3{\pm} 0.5 vs 20.8{\pm}$ 1.5일, p<0.05). CIDR의 삽입시 혈장 progesterone 농도는 $3.6{\pm}$ 2.7 ng/ml 이었으며, 17일과 23일 사이에는 2.1-4.4 ng/ml($3.6{\pm}1.2 ng/ml$) 사이를 유지했다. 혈 장 estradiol-179의 농도는 난포의 발육 및 배란전 배란난포의 성숙을 나타내는 특징적인 변화 양상을 나타래었다. 4마리의 처녀우중 2마리는 CIDR 삽입전 발정주기당 2회의 난포주기를 가진 반면, 나머지 2마리는 주기당 3회의 난포주기를 가졌다. 그렇지만 CIDR의 삽입기간동안 모든 처녀우는 주기당 3회의 발정주기를 가졌다. CIDR의 삽입전 발정주기당 3회의 난포주기 를 갖는 처녀우에서 CRR의 삽입은 세 번째 난포주기에서 배란성 우세난포의 우세기 (dominant phase)를 연장시켰다. 3회의 난포주기를 갖는 2마리에서 CIDR의 삽입후 배란난포 는 존속시간과 우세기가 유의성있게 연장되었다. CIDR의 삽입전 발정주기당 2회의 난포주기 를 갖는 다른 2마리의 처녀우에서 CIDR의 삽입후 우세난포는 곧바로 퇴행되었고 새로운 난 포주기를 형성하였으며, 우세난포의 우세기와 배란난포의 존속기간을 연장시키지 않았다. CRR의 삽입은 CIDR의 삽입후 이어지는 발정주기동안 난포의 발육 및 성장에 영향을 미치 지 않았으며 발정주기의 길이, 난포주기, 혈장 progesterone 및 estradiol-179 농도에 영향을 미치지 않았다. 결과적으로 황체기 후반부에 CIDR의 삽입은 CIDR삽입전 발정주기동안 3회 의 난포주기를 갖는 처녀우에서 배란성 우세난포의 발육과 배란까지의 기간을 연장시켰고 2회 난포주기를 갖는 처녀우에서는 우세난포를 곧바로 퇴행시킨후, 새로운 난포주기를 형성 하였다.