• Journal of Periodontal and Implant Science
• /
• 제38권sup2호
• /
• pp.325-334
• /
• 2008

Purpose: The carrier used as delivery agent for bone morphogenetic proteins(BMPs) should also act as a scaffold for new bone formation. Moreover, bone formation should be predictable in terms of the volume and shape. This study examined the osteogenic effect of macroporous biphasic calcium phosphate (MBCP) block combined with ePTFE membrane as a carrier for recombinant human bone morphogenetic proteins (rhBMP-2). In addition, the additive effect of ePTFE membrane on bone formation was evaluated. Materials and Methods: Eight-millimeter critical sized calvarial defects were created surgically in 28 male Sprague-Dawley rats. The animals were divided into 2 groups containing 14 animals each. The defects were treated with either rhBMP-2/MBCP block (rhBMP-2/MBCP group) or rhBMP-2/MBCP block/ePTFE membrane (rhBMP-2/MBCP/ePTFE group). A disc-shaped MBCP block (3 mm height and 8 mm diameter) was used as the carrier for the rhBMP-2 and ePTFE membrane was used to cover the rhBMP-2/MBCP block. The histologic and histometric parameters were used to evaluate the defects after 2- or 8-week healing period (7 animals/group/healing interval). Results: The level of bone formation in the defects of both groups was significantly higher at 8 weeks than that at 2 weeks (P < 0.05). The ePTFE membrane has no additional effect compared with the rhBMP-2/MBCP block only. However, at 8 weeks, rhBMP-2/MBCP/ePTFE group showed more even bone formation on the top of the MBCP block than the rhBMP-2/MBCP group. Conclusion: These results suggest that the ePTFE membrane has no additive effect on bone formation when a MBCP block is used as a carrier for rhBMP-2.

• Archives of Pharmacal Research
• /
• 제25권5호
• /
• pp.718-723
• /
• 2002

CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin) is a recently-developed synthetic camptothecin analogue and currently under clinical development by Chong Kun Dang Pharm (Seoul, Korea). CKD-602 showed potent topoisomerase inhibitory activity in vitro and broad antitumor activity against various human tumor cells in vitro and in vivo in animal models. This study describes the pharmacodynamics of the immediate and delayed cytotoxicity induced by CKD-602 in a human colorectal adenocarcinoma cell line, HT-29, and its intracellular drug accumulation by HPLC. The present study was designed to address whether the higher activity of CKD-602 with prolonged exposure is due to delayed exhibition of cytotoxicity and/or an accumulation of anti proliferative effect on continuous drug exposure. The drug uptake study was performed to determine whether the delayed cytotoxicity is due to a slow drug accumulation in cells. CKD-602 produced a cytotoxicity that was exhibited immediately after treatment (immediate effect) and after treatment had been terminated (delayed effect). Both the immediate and delayed effects of CKD-602 showed a time dependent decrease in 4IC_{50}$ values. Drug uptake was biphasic and the second equilibrium level was obtained as early as at 24hr, indicating that the cumulative and delayed antitumor effects of CKD-602 were not due to slow drug uptake. On the other hand, CKD-602 treatment was sufficient to induce delayed cytotoxicity after 4hr, however, longer treatment (＞24hr) enhanced its cytotoxicity due to the intracellular accumulation of the drug, which requires 24hr to reach maximum equilibrium concentration. In addition, $C^n$$\times$T=h analysis (n=0.481) indicated that increased exposure times may contribute more to the overall antitumor activity of CKD-602 than drug concentration. Additional studies to determine the details of the intracellular uptake kinetics (e.g., concentration dependency and retention studies) are needed in order to identify the optimal treatment schedules for the successful clinical development of CKD-602.

• 치위생과학회지
• /
• 제15권6호
• /
• pp.800-806
• /
• 2015

이 연구는 triptolide와 L-NAME의 측두하악관절 통증조절효과를 확인하기 위하여 포르말린으로 유도된 측두하악관절 통증모델에서 triptolide와 L-NAME의 소뇌연수조 내 각각의 얄물의 단독 투여에 따른 통증행위반응과 두 약물의 병용 투여에 따른 상호작용이 통증행위반응에 미치는 영향을 평가하여 다음과 같은 결과를 얻었다. 먼저, 관절강 내로 주입한 5% 포르말린($30{\mu}l$)은 유의한 통증행위반응을 유발하였고, 2차 통증행위반응 관찰 시 포르말린 주입 전 $1{\mu}g/10{\mu}l$ triptolide 투여군($163.33{\pm}29.11$회)은 포르말린군($308{\pm}33.04$회)과 비교 시 통증행위반응이 유의하게 감소하였다. $0.1{\mu}g/10{\mu}l$의 L-NAME 투여군의 1, 2차 통증행위반응의 결과, 각각 $5.80{\pm}3.75$회, $92.30{\pm}16.04$회로 포르말린 주입군 $25.4{\pm}6.59$회, $285.60{\pm}29.93$회와 비교 시 유의하게 감소되었다. 다음으로, $1{\mu}g/10{\mu}l$의 triptolide와 $0.01{\mu}g/10{\mu}l$의 L-NAME 병용 투여군에서 1, 2차 통증행위반응이 $0.80{\pm}0.80$회, $96.50{\pm}26.16$회로 나타나 $22.50{\pm}19.15$회, $163.33{\pm}29.11$회로 나타난 $1{\mu}g/10{\mu}l$ trtiptolide군과 비교 시 유의하게 통증행위반응이 경감되었다. 이러한 연구결과는 측두하악관절 통증조절의 예방 및 치료에 있어 활용가능한 천연물로 triptolide가 제시될 수 있으며, 천연물과 화합물들의 병용 투여를 통해 그 효과를 증가시킬 수 있을 것으로 기대된다.

• 한국임상수의학회지
• /
• 제14권2호
• /
• pp.338-348
• /
• 1997

The electrocardiographic (ECG) parameters on unipolar precordial chest leads in the normal Korean native goat of 343 heads as to CV$_{6}$LU, CV$_{6}$LL CV$_{6}$RU, CV$_{6}$RL and V10 have been measured with a 3-channel Elertrocardiograph and computed, analysed. All wave types as positive, negatives biphasic and flatting in the P and T waves appeared in all leads but any special wave type was not shown more than 60%. Average amplitudes with the highest frequent rate in P wave were 81.4$\pm$32.0 $\mu $V (52.3%), 59.6$\pm $ 27.5 $\mu $V (50.5 %) of Positive type in leads CV$_{6}$LU and CV$_{6}$LL, and -5fl.5$\pm $22.6 $\mu $V (44.0%) of negative type in leads VIO, and 51.3% and 44% of flatting type in leads CV$_{6}$RU and CV$_{6}$RL, but flatting type of clinic form appeared frequent rate between 53% and 77% in all leads. In T wave, average amplitudes with the highest frequent rate were 265.0$\pm $97.1 $\mu $V (54.0%) and 212.2$\pm $90.7 $\mu $V (57.0%) of positive type in leads CV$_{6}$LL and CV$_{6}$RL, and -252.8$\pm $90.7 $\mu $V (56.6%) of negative in lead V10, but amplitudes of T waves that positive and negative type appeared similarity frequent ra蛇 ware 208.7$\pm $99.7 $\mu $V (42.1%), -159.0$\pm $81.6 (43.8%) in lead CV$_{6}$LU and 153.2$\pm $139.0 $\mu $V (47.3%), -130.0$\pm $81.4 (43.2%) in lead CV$_{6}$RU, Amplitudes of QRS complex wave forms showed the highest frequent rate were 218.2$\pm $96.4 $\mu $V (47.8%), 308.3$\pm $135.2 $\mu $V (46.8 %), 232.8$\pm $126.5 $\mu $V (58.5%) and 225.3$\pm $89.6 $\mu $V (54.9%) of R type in the leeds CV$_{6}$LU, CV$_{6}$LL, CV$_{6}$RU and CV$_{6}$RL, and were -92.5$\pm $79.1 $\mu $V,479.0 $\pm $116.6 $\mu $V (33.2%) and 212.1 $\pm $86.7 $\mu $V (32.8%) of QR and 05 type in the lead V10. These results in the V10, CV$_{6}$RU, CV$_{6}$RL, CV$_{6}$LU, CV$_{6}$LL. may be not starve to purpose of unipolar precordial chest leads.

• Preventive Nutrition and Food Science
• /
• 제8권4호
• /
• pp.356-364
• /
• 2003

A methanol extract from seeds of Paeonia lactiflora (Paeoniaceae, peony) was found to possess different antiproliferative activities against four different human cancer cell lines: Hela, MCF-7, HepG2 and HT-29. Furthermore, five different methanol (20, 40, 60, 80 and 100 % MeOH) fractions obtained by fractionation of the methanol extract of the seeds on a Diaion HP-20 column exhibited differential antiproliferative effects against the above four cancer cell lines. Among five fractions, the 60 % MeOH fraction showed relatively lower antiproliferative activity on MCF-7 estrogen-sensitive breast cancer cell than the other cancer cell lines. Systematic separation of 60% the MeOH fraction by silica gel and Sephadex LH-20 columns led to the isolation of four known stilbenes, trans-resveratrol (1), trans-(+)- $\varepsilon$ -viniferin (2), gnetin H (3) and suffruticosol B (4). The four stilbenes (1∼4) exerted differential biphasic effects on cell proliferation of MCF-7 cells in a similar manner as genistein, a soybean isoflavone used as a positive reference, in the concentration range from 1.0 to 200 $\mu$M. Three stilbenes (1 ∼ 3) weakly stimulated the proliferation of MCF -7 cells at doses below 10 JIM. However, strong antiproliferative effects on MCF-7 cell were exerted by extract 1 at a dose of 200 JIM, and by 2 and 3 at doses above 25 $\mu$M. In contrast, 4 inhibited the proliferation of MCF-7 cell at a dose below 25 $\mu$M, but stimulated cell proliferation at concentrations of 50 and 100 $\mu$M. All four stilbenes (1∼4) stimulated the proliferation of ROS 17/2.8 osteoblast-like cells in the range of 10$^{-10}$ ∼10$^{-1}$ $\mu$M. Compound 1 exhibited especially potent proliferative activity, although its activity was weaker than that of genistein. Additionally, three resveratrol oligomers (2∼4) also exhibited concentration-dependently moderate proliferative activity, but less than that of 1. These results suggest that resveratrol, and its dimer and trimers from the seeds of Paeonia lactiflora may act as a phytoestrogen, but in a somewhat different manner from that of genistein.

• The Korean Journal of Physiology and Pharmacology
• /
• 제3권1호
• /
• pp.83-91
• /
• 1999

Angiotensin II (ANG II) has a biphasic effect on $Na^+$ transport in proximal tubule: low doses of ANG II increase the $Na^+$ transport, whereas high doses of ANG II inhibit it. However, the mechanisms of high dose ANG II-induced inhibition on $Na^+$ uptake are poorly understood. Thus the aim of the present study was to investigate signal transduction pathways involved in the ANG II-induced inhibition of $Na^+$ uptake in the primary cultured rabbit renal proximal tubule cells (PTCs) in hormonally defined serum-free medium. ANG II $(10^{-9}\;M)-induced$ inhibition of $Na^+$ uptake was blocked by losartan $(10^{-8}\;M,\;AT_1\;antagonist),$ but not by PD123319 $(10^{-8}\;M,\;AT_2\;antagonist)$ (P<0.05). ANG II-induced inhibition of $Na^+$ uptake was also completely abolished by neomycin $(10^{-4}\;M,$ PLC inhibitor), W-7 $(10^{-4}\;M,$ calmodulin antagonist), and $AACOCF_3\;(10^{-6}\;M,\;PLA_2\;inhibitor)$ (P<0.05). ANG II significantly increased $[^3H]arachidonic$ acid (AA) release compared to control. The ANG II-induced $[^3H]AA$ release was blocked by losartan, $AACOCF_3,$ neomycin, and W-7, but not by PD123319. ANG II-induced $[^3H]AA$ release in the presence of extracellular $Ca^{2+}$ was greater than in $Ca^{2+}-free$ medium, and it was partially blocked by TMB-8 $(10^{-4}\;M,$ intracelluar $Ca^{2+}$ mobilization blocker). However, in the absence of extracellular $Ca^{2+},$ it was completely blocked by TMB-8. In addition, econazole $(10^{-6}\;M,$ cytochrome P-450 monooxygenase inhibitor) and indomethacin $(10^{-6}\;M,$ cyclooxygenase inhibitor) blocked ANG II-induced inhibition of $Na^+$ uptake, but NGDA $(10^{-6}\;M,$ lipoxygenase inhibitor) did not affect it. In conclusion, $PLA_2-mediated$ AA release is involved in ANG II-induced inhibition of $Na^+$ uptake and is modulated by $[Ca^{2+}]_i$ in the PTCs.

• International Journal of Oral Biology
• /
• 제31권4호
• /
• pp.127-133
• /
• 2006

[ $H_2O_2$ ], a member of reactive oxygen species (ROS), is known to be involved in the mediation of physiological functions in a variety of cell types. However, little has been known about the physiological role of $H_2O_2$ in exocrine cells. Therefore, in the present study, the effect of $H_2O_2$ on cholecystokinin (CCK)-evoked $Ca^{2+}$ mobilization and amylase release was investigated in rat pancreatic acinar cells. Stimulation of the acinar cells with sulfated octapeptide form of CCK (CCK-8S) induced biphasic increase in amylase release. Addition of $30\;{\mu}M\;H_2O_2$ enhanced amylase release caused by 10 pM CCK-8S, but inhibited the amylase release induced by CCK-8S at concentrations higher than 100 pM. An ROS scavenger, $10\;{\mu}M$ Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, increased amylase release caused by CCK-8S at concentrations higher than 100 pM, although lower concentrations of CCK-8S-induced amylase release was not affected. To examine whether the effect of $H_2O_2$ on CCK-8S-induced amylase release was exerted via modulation of intracellular $Ca^{2+}$ signaling, we measured the changes in intracellular $Ca^{2+}$ concentration $([Ca^{2+}]_i)$ in fura-2 loaded acinar cells. Although $30\;{\mu}M\;H_2O_2$ did not induce any increase in $[Ca^{2+}]_i$ by itself, it increased the frequency and amplitude of $[Ca^{2+}]_i$ oscillations caused by 10 pM CCK-8S. However, $30\;{\mu}M\;H_2O_2$ had little effect on 1 nM CCK-8S-induced increase in $[Ca^{2+}]_i$. ROS scavenger, 1 mM N-acetylcysteine, did not affect $[Ca^{2+}]_i$ changes induced by 10 pM or 1 nM CCK-8S. Therefore, it was concluded that $30\;{\mu}M\;H_2O_2$ enhanced low concentration of CCK-8S-induced amylase release probably by increasing $[Ca^{2+}]_i$ oscillations while it inhibited high concentration of CCK-8S-induced amylase release.

• Journal of Acupuncture Research
• /
• 제17권2호
• /
• pp.231-246
• /
• 2000

Acupuncture has been used for treatment of numerous diseases, especially for pain control in the oriental culture. However, the mechanism of pain control by acupuncture was not clear so far. The present study was examined that the effects of electro-acupuncture (EA) applied to the acu-point of extra-segmental area on modulation of formalin induced pain in Sprague - Dawley rats. In order to apply EA to acu-points in the plantar area of right fore paws, a pair of teflon - coated stainless steel wires were implanted in HT 7 (shin-mun) and PC 7 (dae-neong) 5 days before behavioral test. A behavioral test was performed by means of video camera after injection of 5% formalin ($50{\mu}l$) into the lateral plantar region of left hind paw. EA was delivered by a constant current stimulator at 4~5 mA, 2 ms, and 10 Hz for 30 min. The electromyographic activities were recorded in the biceps femoris muscle under chloral hydrate anesthesia. Test stimuli with 1~9mA were applied to the sural nerve territory including the medial portion of the 4th toe and the lateral portion of the 5th toe. Behavioral responses including favoring, flinching and bitting were occured in the biphasic pattern, such as the lst phase (0~5 min) and the 2nd phase (20~45 min) after formalin injection. However, EA (4~5 mA, 2 ms, 10 Hz) significantly inhibited Che behavioral responses. EMG activities of flexor reflex had a latency of 100~300 ms and thresholds of test stimuli for EMG were 4~5 mA in normal rats. Injection of formalin decreased threshold of test stimuli and increased EMG activities for 2hrs after injection. However, EA significantly inhibited EMG activities of flexor reflex increased by formalin and recovered EMG evoked thresholds. These results suggest that contralateral extra-segmental EA inhibits the first and second phases of formalin induced pain but their mechanism be needed to examine additionally.

• 한국식품과학회지
• /
• 제11권3호
• /
• pp.171-175
• /
• 1979

최근 우리나라의 남부지방에서 재배가 되어 시판되고 있는 파파야를 시료로하여 조효소액을 만들고 단백질 분해효소와 퍼옥시다아제의 열 불활성화 실험을 pH 7.0, $60^{\circ}{\sim}90^{\circ}C$에서 행하고 다음과 같은 열 역학적 자료를 얻었다. 비교적 저온에서는 파파인과 파파야 퍼옥시다아제는 각각 꺽여지는 점을 보였고 단백질 분해효소의 경우 $70^{\circ}C$에서 활성화 엔탈피(enthalpy of activation) 91.4 kJ/mol, 활성화 엔트로피 (entropy of activation) -49.6 J/mol K, 활성화 자유에너지 (free energy of activation) 108.5 kJ/mol 이었고 퍼옥시다아제의 열 불활성화에서는 $70^{\circ}C$에서 활성화 엔탈피 168.5 kJ/mol, 활성화 엔트로피 $200.4\;J/mol{\cdot}K$, 활성화 자유에너지 99.7 kJ/mol 이었다. 파파인은 비교적 열에 안정하여 연육소로 사용할 수 있는 가능성을 보였고 파파야 퍼옥시다아제도 카탈라아제보다는 열에 안정하여 열처리 공정의 생화학적 지시약(indicator)으로 사용하는 편이 좋을 듯하다.

• Food Science and Biotechnology
• /
• 제18권3호
• /
• pp.661-666
• /
• 2009

The heat tolerance and the inactivation kinetics of peroxidase (POD) and polyphenol oxidase (PPO) in pineapples (Ananas comosus) were studied in the temperature range $45-95^{\circ}C$. The kinetic parameters, such as deactivation rate constant (k), activation energy ($E_a$), and decimal reduction rate (D) of the thermal inactivation process, were determined. POD in pineapples showed biphasic inactivation behavior at temperatures range $45-75^{\circ}C$ but was monophasic at $85-95^{\circ}C$. This indicate that POD has 2 isozymes, namely heat labile and heat resistant, with $E_a$ of 68.79 and 93.23 kJ/mol, respectively. On the other hand, the heat denaturation of pineapple PPO could be described as simple monophasic first-order behavior with $E_a$ of 80.15 kJ/mol. Thus, the results of this study is useful in blanching technology where it shows a shortened time with higher temperature can be applied. The determination of the heat tolerance and inactivation POD and PPO, at different temperature range as done in the present work, was very important to improve the blanching process. This also will help to optimize the pineapple canning process which is one of the most important food industries in many tropical regions.