• 약학회지
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• 제44권6호
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• pp.511-520
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• 2000

Various bupivacaine-loaded microspheres were prepared from poly (d,l-lactide) (PLA) or poly (d,l-lactic-co-glycolide) (PLGA) by a solvent evaporation method for the sustained release of drug. PLA and PLGA microspheres were prepared by w/o/w and w/o/o multiple emulsion solvent evaporation, respectively. The effects of process conditions such as emulsification speed, emulsifier type, emulsifier concentration and internal/external phase ratio on the characteristics of microspheres were investigated. The prepared microspheres were characterized for their drug loading, size distribution, surface morphology and release kinetics. Drug loading efficiency was higher in the microspheres prepared by w/o/o multiple emulsion than that by w/o/w multiple emulsion method, because the solubility of bupivacaine HCI was decreased in oil phase compared with water phase. The prepared microspheres had an average diameter between 1 and $2\;{\mu}M$ in all conditions of two methods. In morphology studies the PLA microspheres showed an irregular shape and smooth surface, but PLGA microspheres had a spherical shape and smooth surface. The release pattern of the drug from microspheres was evaluated on the basis of the burst effect and the extent of the release after 24h. The in vitro release of bupivacaine HCl from microspheres showed a large initial burst release and $60{\sim}80%$ release within one day in all conditions of two methods. The extents of the burst release against PLA and PLGA microspheres were $30{\sim}50%$ and $50{\sim}80%$ within 20min, respectively. This burst release seems to be due to the smaller size of microspheres and the solubility of drug in water.

• Journal of Forest and Environmental Science
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• 제34권4호
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• pp.338-351
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• 2018

This study was conducted in a long-term experimental forest in the central hardwoods region of southwestern Michigan to retrospectively examine the role of past forest management practices and climate on red oak (Quercus rubra L.) productivity. Initially, in 1971, plots within the experimental forest were treated separately with a clearcut and shelterwood regeneration harvest in an attempt to increase red oak regeneration. From 1987-1989, a new study was initiated within a portion of the clearcut and shelterwood plots to evaluate the effectiveness of additional oak crop tree release using mechanical and chemical applications. Cumulative diameter and mortality rates of 719 red oaks were monitored across the four silvicultural treatments: Clearcut-A (clearcut without additional release treatment), Clearcut-B (clearcut with additional release treatment), Shelterwood-A (shelterwood without additional release), and Shelterwood-B (shelterwood with additional release) plus an untreated control. Increment cores were obtained from red oak trees and neighboring competitor species. Tree-ring analyses (dendrochronology) were applied to examine the effect of these silvicultural treatments and climatic factors (temperature and precipitation) on red oak productivity. The results indicated that crop tree release following a clearcut or shelterwood harvest reduced mortality rates and thus increased survival of red oak. Red oak in control plots or plots only receiving the initial regeneration harvesting treatment and no additional competition release were negatively affected by climatic stress, which included summer moisture stress. In contrast, red oak in plots that received the competition release treatment from shade tolerant tree species not only had higher tree level productivity (i.e., tree basal area) and lower mortality rates, but were also relatively more resilient to climatic stress by showing limited or no associations between climate and growth.

• 대한수의학회지
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• 제39권6호
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• pp.1073-1080
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• 1999

Previous studies suggested that the inhibition of thyroxine ($T_4$) release by ${\alpha}_1$-adrenoceptor and muscarinic receptor stimulation results in activated protein kinase C (PKC) from mouse and guinea pig thyroids. In the present study, the effect of carbachol, methoxamine, phorbol myristate acetate (PMA), and R59022 on the release of $T_4$ from the mouse, rat, and guinea pig thyroids was compared to clarify the role of PKC in the regulation of the release of $T_4$. The thyroids were incubated in the medium containing the test agents, samples of the medium were assayed for $T_4$ by EIA kits. Forskolin, an adenylate cyclase activator, chlorophenylthio-cAMP sodium, a membrane permeable analog of cAMP, and isobutyl-methylxanthine, a phosphodiesterase inhibitor, like TSH (thyroid stimulating hormone), enhaced the release of $T_4$ from the mouse, rat, and guinea pig thyroids. Methoxamine, an ${\alpha}_1$-adrenoceptor agonist, inhibited the TSH-stimulated release of $T_4$ in mouse, but not rat and guinea pig thyroids. In contrast, carbachol, a muscarinic receptor agonist, inhibited the release of $T_4$ in guinea pig, but not mouse and rat thyroids. These inhibition were reversed by prazosin, an ${\alpha}_1$-adrenoceptor antagonist or atropine, a muscarinic antagonist or $M_1$- and $M_3$-muscarinic antagonists, in mouse or guinea pig thyroids. In addition, staurosporine, a PKC inhibitor, reversed methoxamine or carbachol inhibition of TSH stimulation. Furthermore, PMA, a PKC activator, and R59022, a diacylglycerol (DAG) kinase inhibitor, inhibited the TSH-stimulated release of $T_4$ in mouse, rat, and guinea pig thyroids. These inhibition were blocked by staurosporine. These findings suggest that the activation of receptor or DAG inhibits TSH-stimulated $T_4$ release through a PKC-dependent mechanism in thyroid gland.

• 한국토양비료학회지
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• 제35권6호
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• pp.381-386
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• 2002

관행시비 (4회 분시)에 비해 완효성 비료 2회 분시가 수량이 12.5% 증수하였으나, 1회 분시는 $6{\pm}3%$ 감소하였다. 관행시비에 비해 완효성 비료 2회 분시가 총질소, 총 아미노산, 엽록소, 비타민 C 함량과 감칠맛 주성분인 theanine, glutamic acid, arginine 함량이 많았고, tannin 함량은 적은 편이였으나, 완효성 비료 1회 분시는 2회분시와는 반대의 경향을 나타냈다. 형상, 향, 맛 등 제다품질은 완효성 비료 2회분시가 1회분시나 관행 시비 4회 분시에 비해 우수하였다. 결론적으로 완효성 비료의 분시효과가 우수한 이유는 비료성분이 서서히 용출되어 나와 효과적으로 작물에 공급되는 한편 비료성분의 손실을 줄일수 있었기 때문으로 판단된다.

• Restorative Dentistry and Endodontics
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• 제21권1호
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• pp.403-424
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• 1996

Cell culture methods have been used to assess the cytotoxicity of dental materials. Different paramaters are used to monitor cytotoxic effects. But it is difficult to compare each investigator's results with different methods. The objective of this study was to investigate cytotoxic effect of several retrograde filling materials according to cell lines and assay methods. Cytotoxicity of Bestalloy (Dogmyung, Korea), Prisma APH(Densply International Inc., U.S.A.), Clearfil FII (Kuraray Co., Japan), Fuji II (GC Co., Japan), Fuji II LC (GC Co., Japan) and IRM (Densply Co., U.S.A.) on L929, 3T3 and KB permanent cell lines was measured. Radiochromium, Lactate dehydrogenase (LDH) release method and colorimetric assays, namely neutral red (NR) and MTT were used. Each material was mixed according to the manufacturer's instruction. They were tested as solid and extracted state. Cell culture media were added to each mixed or solid materials then the solution was collected and used as extract solutions. Solid Fuji II showed mild cytotoxicity on three cell lines using radiochromium release method. There was no difference in cytotoxicity of extract solution group using radiochromium release method. In colorimetric assay immediate Fuji II group and all the IRM groups showed severe cytotoxic effect. Difference in cyctotoxicity was due to rather kinds of cell lines than assay methods. Solid Fuji II and IRM showed mild cytotoxicity on three cell lines. But extract solutions had different cytotoxic effect according to cell lines using LDH release assay. Light-cured glass ionomer had mild to moderate degree of cytotoxicity on three cell lines. Cytotoxicity was affected by specimen prepaton. Susceptibility of each cell ines were also affected by assay emthods. It was suggested that cytotoxicity study using only one cell line and/or assay method might not accurately reflect the real toxic nature of dental biomaterials.

• BMB Reports
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• 제29권1호
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• pp.22-26
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• 1996

Agents that activate or inhibit the $Ca^{2+}$ release channel in cardiac sarcoplasmic reticulum (SR) were tested for their abilities to affect the activity of the SR $Ca^{2+}$-ATPase. Vesicles of junctional SR (heavy SR, HSR) from terminal cisternae were prepared from porcine cardiac muscle by density gradient centrifugation. The steady-state activity of $Ca^{2+}$-ATPases in intact HSR vesicles was/$347{\pm}5\;nmol/min{\cdot}mg$ protein (${\pm}$ SD). When the HSR vesicles were made leaky, the activity was increased to $415{\pm}5\;nmol/min{\cdot}mg$ protein. This increase is probably due to the uncoupling of HSR vesicles. Caffeine (10 mM), an agonist of the SR $Ca^{2+}$ release channel, increased $Ca^{2+}$-ATPase activity in the intact HSR vesicle preparation to $394{\pm}30\;nmol/min{\cdot}mg$ protein. However, caffeine had no significant effect in the leaky vesicle preparation and in the purified $Ca^{2+}$-ATPase preparation. The effect of caffeine on SR $Ca^{2+}$-ATPase was investigated at various concentrations of $Ca^{2+}$. Caffeine increased the pump activity over the whole range of $Ca^{2+}$ concentrations, from $1\;{\mu}M$ to $250\;{\mu}M$, in the intact HSR vesicles. When the SR $Ca^{2+}$-ATPase was inhibited by thapsigargin, no caffeine effect was observed. These results imply that the caffeine effect requires the intact vesicles and that the increase in $Ca^{2+}$-ATPase activity is not due to a direct interaction of caffeine with the enzyme. We propose that the activity of SR $Ca^{2+}$-ATPase is linked indirectly to the activity of the $Ca^{2+}$ release channel (ryanodine receptor) and may depend upon the amount of $Ca^{2+}$ released by the channels.

• 대한한의학회지
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• 제17권1호
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• pp.9-20
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• 1996

Oxygen free radicals can generated during metabolic processes in normal cells and by exposure of cells to toxic substances. These radicals have been recogenized to playa critical role in several pathological conditions including carcinogenesis and aging, and they have been implicated in pathogenesis of various diseases such as seizure, Alzheimer's disease, Parkinson's disease, myocardial infarction, respiratory distress syndrome, and rheumatoid arthritis. This study was undertaken to determine if Juglandis semen herb-acupuncture solution (JSHAS) has a protective effect against cell injury caused by oxidants, t-butylhydroperoxide (t-BHP) and $H_{2}O_2$. Cell injury was estimated by measuring lactate dehydrogenase (LDH) release and lipid perexidation was estimated by measurimg malondialdehyde, a product of lipid peroxidation. JSHAS significantly prevented LDH release induced by t-BHP or $H_{2}O_2$ in a dose-dependent manner at concentrations of 0.5-10%. Such protective effect was observed in control tissues untreated with oxidants. JSHAS, at 5% concentration, significantly reduced LDH release even when the concentrations of t-BHP and $H_{2}O_2$ increased to 5 and 200 mM, respectively. JSHAS, at 5% concentration, significantly reduced the lipid peroxidation by t-BHP and $H_{2}O_2$. These results indicate that JSHAS prevents cell injury and lipid peroxidation induced by oxidants in rabbit kidney cells. However, the underlying mechanisms remain to determined.

• Journal of Pharmaceutical Investigation
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• 제38권2호
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• pp.93-98
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• 2008

The drug-eluting stent (DES) implantation is a widely acceptable treatment for coronary heart disease. It was reported that iron chelator had anti-proliferative effect on human vascular smooth muscle cells (HA-VSMCs). In this study, tetraphenylporphine (TPP) was selected as an iron chelator and drug for DES. MTT assay showed that TPP had antiproliferative effect on HA-VSMCs. TPP and polycaprolactone (PCL) were coated onto stainless steel plate using a spraycoating method. From the surface morphology examination of the coated plate by SEM, smooth polymer coating layer could be observed. The thickness of coating layer could be controlled by changing repeating time of coating. From in vitro release test, sustained release of TPP was observed from plate during two weeks. Thus, TPP as iron chelator can be used as drug for stent coating because of its antiproliferative effect and sustain release profile.

• 폴리머
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• 제31권4호
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• pp.329-334
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• 2007

경구를 통한 약물전달시스템 중 하나인 삼투압을 이용한 삼투정 펠렛의 제조는 타블렛 제형이 갖는 제조 공정상의 복잡함과, 생산비용 등의 문제들을 줄이고자 시도되었다. 삼투정 펠렛은 수팽윤성 시드층과 약물층 그리고 반투막층으로 구성되었으며, 이중에서 반투막층은 약물의 방출을 조절하는 중요한 역할을 한다. 이번 연구에서는 반투막층으로 사용되는 Eudragit RL과 RS의 비에 대한 영향과 코팅두께에 따른 약물방출 거동을 확인하고자 하였다. 모델약물인 니페디핀을 포함한 삼투정 펠렛의 제조는 유동층 코팅기를 이용하여 제조하였으며, 비교적 높은 코팅 수율과 $1300{\sim}1500\;{\mu}m$ 크기의 펠렛을 얻었다. 얻어진 펠렛의 Eudragit RL과 RS의 비에 따른 약물방출 거동을 보면, Eudragit RL의 비가 증가할수록 약물의 방출은 증가함을 확인하였다. 이는 Eudragit RL이 RS보다 친수성 4차 암모늄 그룹을 더 많이 갖기 때문이다. 또한 반투막의 코팅 두께가 증가할수록 약물의 방출이 지연됨을 확인하였다. 반투막과 모델약물의 pH의 변화에 대한 약물방출의 영향을 알아보기 위하여 pH 1.2, 6.5, 6.8, 7.2의 서로 다른 pH에서 실험을 실시하였으며, pH의 변화에 관계없이 약물방출이 안정적으로 일어남을 확인하였다. 이번 실험을 통하여 삼투정 펠렛의 약물방출은 펠렛의 반투막 조성과 코팅두께에 의존함을 확인하였다.

• Natural Product Sciences
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• 제27권2호
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• pp.86-98
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• 2021

This study was designed to characterize the effect of ginsenoside-Rg2 (Rg2), one of panaxatriol saponins isolated from Korean ginseng root, on the release of catecholamines (CA) in the perfused model of the rat adrenal medulla, and also to establish its mechanism of action. Rg2 (3~30 µM), administered into an adrenal vein for 90 min, depressed acetylcholine (ACh)-induced CA secretion in a dose- and time-dependent manner. Rg2 also time-dependently inhibited the CA secretion induced by 3-(m-chloro-phenyl-carbamoyl-oxy)-2-butynyltrimethyl ammonium chloride (McN-A-343), 1.1-dimethyl-4-phenyl piperazinium iodide (DMPP), and angiotensin II (Ang II). Also, during perfusion of Rg2, the CA secretion induced by high K⁺, veratridine, cyclopiazonic acid, methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-pyridine-5-carboxylate (Bay-K-8644) depressed, respectively. In the simultaneous presence of Rg2 and N^ω-nitro-L-arginine methyl ester hydrochloride ʟ-NAME), the CA secretion induced by ACh, Ang II, Bay-K-8644 and veratridine was restored nearly to the extent of their corresponding control level, respectively, compared to those of inhibitory effects of Rg2-treatment alone. Virtually, NO release in adrenal medulla following perfusion of Rg2 was significantly enhanced in comparison to the corresponding spontaneous release. Also, in the coexistence of Rg2 and fimasartan, ACh-induced CA secretion was markedly diminished compared to the inhibitory effect of fimasartan-treated alone. Collectively, these results demonstrated that Rg2 suppressed the CA secretion induced by activation of cholinergic as well as angiotensinergic receptors from the perfused model of the rat adrenal gland. This Rg2-induced inhibitory effect seems to be exerted by reducing both influx of Na⁺ and Ca²⁺ through their ionic channels into the adrenomedullary cells as well as by suppressing Ca²⁺ release from the cytoplasmic calcium store, at least through the elevated NO release by activation of NO synthase, which is associated to the blockade of neuronal cholinergic and AT₁-receptors. Based on these results, the ingestion of Rg2 may be helpful to alleviate or prevent the cardiovascular diseases, via reduction of CA release in adrenal medulla and consequent decreased CA level in circulation.