• Archives of Pharmacal Research
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• 제27권6호
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• pp.662-669
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• 2004

The highly water-soluble monomethoxypoly(ethyleneglycol) (mPEG) prod rugs of cyciosporin A(CsA) were synthesized. These prod rugs were prepared by initially preparing intermediate in the form of carbonate at the 3'-positions of CsA with chloromethyl chloroformate, in the pres-ence of a base to provide a 3'-carbonated CsA intermediate. Reaction of the CsA intermediate with mPEG derivative in the presence of a base provides the desired water-soluble prod rugs. As a model, we chose molecular weight 5 kDa mPEG in the reaction with CsA to give water soluble prodrugs. To prove that the prod rug is decomposed in the body to produce CsA, the enzymatic hydrolysis test was conducted using human liver homogenate at $37^{\circ}C$. The prodrug was decomposed in human liver homogenate to produce the active material, CsA, and the hydrolysis half-life ($t_{1/2}$) of the prodrug, KI-306 was 2.2 minutes at $37^{\circ}C$. However, a demon-stration of non-enzymatic conversion in pH 7.4 phosphate buffer was provided by the fact that the half-life ($t_{1/2}$) is 21 hours at 37$^{\circ}C$. The hydrolysis test in rat whole blood was also conducted. The hydrolysis was seen with half-life ($t_{1/2}$) of about 9.9, 65.0, 14.2, 3.4, 2.1 9.5, and 1.6 minutes for KI-306, 309, 312, 313, 315, 316, and 317, respectively. This is the ideal for CsA prodrug. The pharmacokinetic study of the prodrug, KI-306, in comparison to the commer-cial product (Sandimmune Neoral Solution) was also carried out after single oral dose. Each rat received 7 mg／kg of CsA equivalent dose. Especially, the prodrug KI-306 exhibits higher AUC and $C_{max}$ than the conventional Neoral. The AUC and $C_{max}$ were increased nearly 1.5 fold. The kinetic value was also seen with $T_{max}$ of about 1.43 and 2.44 hours for KI-306 and Neoral, respectively.

• Archives of Pharmacal Research
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• 제29권10호
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• pp.874-878
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• 2006

Methyl gallate (MG) is a medicinal herbal product that is isolated from Paeonia lactiflora that inhibits cyclooxygenase-2 (COX-2) dependent phases of prostaglandin $D_2\;(PGD_2)$ generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with an $IC_{50}$ values of $17.0\;{\mu}M$. This compound also found inhibited the COX-2-dependent conversion of the exogenous arachidonic acid to $PGD_2$ in a dose-dependent manner with an $IC_{50}$ values of $190\;{\mu}M$, using a COX enzyme assay kit. However, at concentrations up to $80\;{\mu}M$, MG did not inhibit COX-2 protein expression in BMMC, indicating that MG inhibits COX-2 activity directly. Furthermore, MG consistently inhibited the production of leukotriene $C_4\;(LTC_4)$ in a dose dependent manner, with an $IC_{50}$ value of $5.3\;{\mu}M$. These results demonstrate that MG has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity, which might provide the basis for novel anti-inflammatory drugs.

• 한국식품영양학회지
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• 제17권4호
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• pp.347-355
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• 2004

초석잠 메탄올 추출물이 뇌신경전달물질과 관련이 있는 acetylcholine esterase, monoamine oxidase 및 xanthine oxidase의 활성억제효과에 대하여 실험하였다. 실험관내에서 초석잠 추출물을 각각 100 및 200mg/kg씩 첨가한 다음 실험한 결과 첨가농도가 증가할수록 과산화지질의 생성을 억제하여 용량 의존형으로 나타났다. 쥐를 대상으로 20일간 투여한 동물실험에서는 초석잠 추출물 100 mg/kg을 식이에 혼합하여 투여한 결과 지질 과산화의 생성을 억제하였다. Acetylcholine esterase의 활성의 경우 초석잠 추출물을 100 mg/kg 투여한 결과 대조군에 비하여 효소활성이 23.11%로 억제되었고, monoamine oxidase 및 xanthine oxidase 활성이 각각 21.93% 및 63.58%로 억제되었다. 그리고 초석잠 추출물을 100 mg/kg을 투여한 경우 xanthine dehydrogenase로부터 xanthine oxidase로의 형전환비율은 28%로 현저하게 억제되었다. 또한, Xanthine dehydrogenase로부터 oxidase로의 형전환비율을 실험한 결과 정상상태에 비하여 억제됨을 알 수 있었다.

• Animal Bioscience
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• 제34권11호
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• pp.1802-1810
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• 2021

Objective: The purpose of this study was to evaluate the effects of supplementing herbal active ingredients (YGF251) which can promote the secretion of insulin-like growth factor-1 (IGF-1) in the diet on production performance, egg quality, blood hematology, and excreta gas emission in laying hens. Methods: A total of 288 ISA Brown (41-week-old) laying hens with an initial body weight of 1.83±0.68 kg were randomly assigned to 1 of 4 dietary treatments in a randomized block design based on body weight. Each treatment had 12 replicate cages having 6 adjacent cages per replicate (hens are kept in cages alone). The experimental period was 35 days. Dietary treatments were based on the corn-soybean meal-wheat-based basal diet and supplemented with 0.00%, 0.05%, 0.10%, or 0.15% YGF251. Results: There was a linear increased egg weight in weeks 1 to 5 (p<0.05), egg mass in week 1 (p<0.05) and weeks 1 to 5 (p<0.05), egg strength on day 7 (p<0.05), 21 (p<0.01), and 35 (p<0.01), eggshell thickness on day 21 (p<0.05) and 35 (p<0.01), haugh unit on day 21 (p<0.01) and 35 (p<0.05), serum IGF-1 concentration on day 21 (p<0.05) and 35 (p<0.01), and serum total protein concentration on day 35 (p<0.05) were observed with the supplementing YGF251 increased in the diet, while feed conversion ratio in weeks 1 to 5 (p<0.05) and excreta ammonia emission (p<0.01) decreased linearly with the dose of YGF251 increased. Conclusion: Dietary supplementation of YGF251 positively affected the production performance and egg quality of laying hens through increasing serum IGF-1 concentration in a dose-dependent manner. Moreover, YGF251 supplementation improved barn environment by reducing excreta noxious gas emission.

• 한국수산과학회지
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• 제51권6호
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• pp.688-696
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• 2018

This study investigated the effects of ozone-produced oxidants (OPO) on the growth, hematology, and histology of olive flounder Paralichthys olivaceus (average weight 500 g), raised in an ozonated semi-recirculating aquaculture system. The system was ozonated to maintained OPO concentrations of 0.004 (Control), 0.014 (OPO15), and 0.025 (OPO25) mg $Cl_2/L$ in culture tanksfor 26 days. The specific growth rate, feed conversion ratio, and survival rate did not significantly differ among the groups (P>0.05), while the daily feeding rate decreased OPO-dose-dependently (P<0.05). OPO appeared to affect the gill, hepatopancreas, and kidney tissues of fish from ozonated tanks. Hematologically, OPO affected some blood indices. The levels of chloride, glucose, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase were significantly increased in the ozonated groups, while the total cholesterol and cortisol decreased dose-dependently. These results imply that long-term exposure of olive flounder to an OPO concentration ${\geq}0.014mg\;Cl_2/L$ might result in damage to the gill, hepatopancreas, and kidney tissues and cause physiological stress, albeit with no apparent short-term effects on growth or survival.

• 대한약리학회지
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• 제12권1호
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• pp.69-73
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• 1976

A combined syrup preparation of pyrantel pamoate and oxantel pamoate containing 50mg/ml of respective anthelminthics was evaluated on the efficacy to treat the human intestinal nematodes. Total 24 cases were treated with oral administration of above preparation 10 mg/kg body weight by single dose. The results were summarized as follows: 1. Out of 21 cases of Ascaris lumbricoides infection, 19 (90.5%) turned to be egg negative on 21 days after treatment and egg-reduction rate was 99.7%. 2. 17 cases out of 19 cases infected with Trichocephalus trichiurus were egg negative after treatment (84.2%) and egg reduction rate was 60.6%. 3. As for Ancylostoma duodenale infection, egg negative conversion rate was 88.9% and egg reduction rate was 98.1% by single oral administration among 9 infected cases. 4. In Enterobius vermicularis infection, all of 17 cases gave negative anal swab on 21th day after the treatment. From the above results, it was assumed that the anthelminthic activities of pyrantel pamoate and oxantel pamoate were not potentiated by the mixture of two kinds of drugs but showed simple additive effect.

• Nutrition Research and Practice
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• 제5권3호
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• pp.214-218
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• 2011

Diets based on carbohydrates increase rapidly the blood glucose level due to the fast conversion of carbohydrates to glucose. High glucose diets have been known to induce many lifestyle diseases. Here, we demonstrated that high glucose diet shortened the lifespan of Caenorhabditis elegans through apoptosis induction. Control adult groups without glucose diet lived for 30 days, whereas animals fed 10 mg/L of D-glucose lived only for 20 days. The reduction of lifespan by glucose diet showed a dose-dependent profile in the concentration range of glucose from 1 to 20 mg/L. Aging effect of high glucose diet was examined by measurement of response time for locomotion after stimulating movement of the animals by touching. Glucose diet decreased the locomotion capacity of the animals during mid-adulthood. High glucose diets also induced ectopic apoptosis in the body of C. elegans, which is a potent mechanism that can explain the shortened lifespan and aging. Apoptotic cell corpses stained with SYTO 12 were found in the worms fed 10 mg/L of glucose. Mutation of core apoptotic regulatory genes, CED-3 and CED-4, inhibited the reduction of viability induced by high glucose diet, which indicates that these regulators were required for glucose-induced apoptosis or lifespan shortening. Thus, we conclude that high glucose diets have potential for inducing ectopic apoptosis in the body, resulting in a shortened lifespan accompanied with loss of locomotion capacity.

• Journal of Microbiology and Biotechnology
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• 제11권6호
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• pp.1099-1101
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• 2001

In an attempt to search for serotonin N-acetyltransferase (arylalkylamine N-acetyltransferasem, AA-NAT) inhibitors from microbial metabolites, we fecund the culture broth of Penicillium sp. 80722 which showed a strong inhibitory activity against AA-NNT. The active principle has been identified as citrinin hydrate through bioassay-guided fractionation of cultural broth, and structure elucidation derived by spectroscopic analyses. Citrinin hydrate inhibits AA-NAT with an $IC_50$ value of $173{\mu}M$ in a dose-dependent manner. Although citrinin hydrate was previously isolated as human rhinovirus 3C-protease inhibitor, this was recognized as the first AA-NAT inhibitor isolated from natural sources.

• Asian-Australasian Journal of Animal Sciences
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• 제17권6호
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• pp.820-824
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• 2004

The study was to see the effect of administration of ruminal fungi on feed intake, growth rate, rumen fermentation and nutrient digestion of calves (Tharparkar$\times$Holstein-Friesian, average age: 10 months, average body weight: 130 kg). The 6 calves in first group were fed a mixture consisted of 50% wheat straw and 50% concentrate (Maize 62%, Groundnut cake 35%, Mineral mix. 2% and Common salt 1%) along with 1 kg green oats $animal^{-1}$ $day^{-1}$ while second group calves were fed the above-mentioned diet in addition to a dose of 160 ml ($10^{6}$ CFU/ml) fungal culture $calf^{-1}$ $week^{-1}$. The average dry matter intake per day was slightly lowered in fungal fed calves yet feed conversion ratio was higher. The average daily weight gain was significantly higher (15.37%) in fungal administered group as compared to control. The nutrient digestibility was increased for crude fibre, NDF and ADF with fungal administration. Digestible energy value of straw-based diet in terms of percent TDN also increased. The pH and $NH_{3}$-N were lower whereas TVFA, total-N, TCA-N and number of zoospores were higher in rumen liquor in fungal administered group.

• Journal of Radiation Protection and Research
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• 제29권1호
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• pp.41-48
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• 2004

A safety assessment code, called SAGE (Safety Assessment Groundwater Evaluation), has been developed to describe post-closure radionuclide releases and potential radiological doses for low- and intermediate-level radioactive waste (LILW) disposal in an engineered vault facility in Korea. The conceptual model implemented in the code is focused on the release of radionuclide from a gradually degrading engineered barrier system to an underlying unsaturated zone, thence to a saturated groundwater zone. The radionuclide transport equations are solved by spatially discretizing the disposal system into a series of compartments. Mass transfer between compartments is by diffusion/dispersion and advection. In all compartments, radionuclides ate decayed either as a single-member chain or as multi-member chains. The biosphere is represented as a set of steady-state, radionuclide-specific pathway dose conversion factors that are multiplied by the appropriate release rate from the far field for each pathway. The code has the capability to treat input parameters either deterministically or probabilistically. Parameter input is achieved through a user-friendly Graphical User Interface. An application is presented, which is compared against safety assessment results from the other computer codes, to benchmark the reliability of system-level conceptual modeling of the code.