• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.63-67
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• 2016

Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose ($1{\times}10^6cells/kg$), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.

• Radiation Oncology Journal
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• 제35권1호
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• pp.32-38
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• 2017

Purpose: Several accelerated partial breast radiation (APBR) techniques have been investigated in patients with early-stage breast cancer (BC); however, the optimal treatment delivery techniques remain unclear. We evaluated the feasibility and toxicity of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I BC, using a novel fractionation schedule. Materials and Methods: Forty-two patients aged ${\geq}65$ years, with stage I BC who underwent breast conserving surgery were enrolled in a phase I/II study evaluating APBR using IMRT. Forty eligible patients received 40 Gy in 4 Gy daily fractions. Patients were assessed for treatment related toxicities, and cosmesis, before APBR, during, and after completion of the treatment. Results: The median age was 73 years, median tumor size 0.8 cm and the median follow-up was 54 months. The 5-year locoregional control was 97.5% and overall survival 90%. Erythema and skin pigmentation was the most common acute adverse event, reported by 27 patients (69%). Twenty-six patients (65%) reported mild pain, rated 1-4/10. This improved at last follow-up to only 2 (15%). Overall the patient and physician reported worst late toxicities were lower than the baseline and at last follow-up, patients and physicians rated cosmesis as excellent/good in 93% and 86 %, respectively. Conclusion: In this prospective trial, we observed an excellent rate of tumor control with daily APBR. The acceptable toxicity profile and cosmetic results of this study support the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.

• Biomolecules & Therapeutics
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• 제14권2호
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• pp.83-89
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• 2006

The main aim of this study was to characterize the pharmacological profile of flavonoids utilizing behavioral tests and to investigate how the psychopharmacological activities of wogonin, baicalein and oroxylin A are different. Wogonin, baicalein and oroxylin A were intraperitoneally injected as dosages of 2.5, 5, 10 and 20 mg/kg. In the locomotor activity, Rota-rod test, and elevated plus-maze tests, the behavioral parameters were analyzed by automatic systems. Thiopental induced sleeping time was measured. Water extract of S. baicalensis didn't exhibit sedative effect. Wogonin and bacalein exhibited anxiolytic activity although it was less potent than buspirone. Wogonin and baicalein decreased locomotor activity at a dose of 10 mg/kg. Wogonin also shortened significantly running time on the rota-rod at doses of 5 and 10 mg/kg. Wogonin and baicalein enhanced sleeping at doses of 5 and 10 mg/kg. These results indicate that wogonin produce anxiolysis with sedation and so did bacalein with mild sedation. On the contrary, oroxylin A enhanced running activity on the rotarod and did't depress locomotor activity. Oroxylin A significantly hindered sleeping rather than helped it at doses of 5 and 10 mg/kg. Oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This study demonstrates that wogonin and bacalein exhibited anxiolytic activity with mild sedation, but oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This result indicates that anxiolytic effect without sedation induced by Scutellaria baicalensis is produced by combination of flavonoids.

• 생약학회지
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• 제43권4호
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• pp.308-315
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• 2012

Opuntia humifusa known as the Eastern prickly pear have been used as a treatment of burns, diarrhea, asthma, rheumatism, gonorrhea, and diabetes in alternative medicine. O. humifusa is widely cultivated in the middle and southern provinces of Korea and distributed in North America. The aim of this study is to investigate anti-diabetic effect of O. humifusa stem (OHS) water or 80% MeOH extract using 3T3-L1 adipocytes and db/db mice animal models. OHS 80% MeOH extract at a dose of $250{\mu}g/ml$ significantly increased the glucose uptake and lipid accumulation compared with the control in 3T3-L1 adipocytes. Blood glucose, plasma total cholesterol and triglyceride levels were significantly reduced by oral treatment of OHS 80% MeOH extract (200 mg/kg BW) for 6 weeks in db/db mice. Also, the oral treatment of OHS 80% MeOH extract slightly changed the plasma insulin and insulin resistance levels in db/db mice, but were no significance in comparison to control. Glucose transporter(GLUT)4 expressions of adipose tissue and muscle were significantly increased more than that in the control. Therefore, these results suggest that OHS 80% MeOH extract inhibits the blood glucose level through regulation of lipid profile, insulin resistance, and GLUT4 expression in db/db mice and its diabetic effect is effective more than water extract.

• 한국식품영양학회지
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• 제33권5호
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• pp.544-550
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• 2020

The purpose of this study was to examine the effects of Atractylodes lancea (A.l.) in a dose-dependent manner on lipid levels and plasma glucose in diabetic rats induced with streptozotocin (STZ). The Sprague-Dawley rats were randomly classified into five groups: normal, STZ-control and three experimental groups [A.l.-1, diabetic treated with ethanolic extract of A.l. (1 g/kg b.w.), A.l.-2, diabetic administered with ethanolic extract of A.l. (2 g/kg b.w.), and A.l.-3, diabetic administered with ethanolic extract of A.l. (3 g/kg b.w.)]. The normal and STZ-control group were fed an AIN-93 diet and the three experimental groups were administered with A.l. extract at doses of 1, 2, and 3 g/kg b.w./day, respectively, for 14 days. The plasma glucose levels in all the experimental groups were significantly lower than the STZ-control group after 14 days of treatment. The total cholesterol of the A.l.-3 and triglyceride levels, atherogenic index (AI) of all three experimental groups were significantly lower than the STZ-control group. The ALT and AST activities at A.l.-2, A.l.-3 were significantly lower than the STZ-control group. This result that demonstrate the administration of Atractylodes lancea can reduce hyperglycemia and hyperlipidemia risk in diabetic rats.

• Parasites, Hosts and Diseases
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• 제35권3호
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• pp.181-188
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• 1997

닭에 있어서 닭와포자충 갉염이 면역반응에 미치는 영향을 규명하기 위한 기초적 연구리 일환으로 파브리시우스낭의 병리조직학적 소견을 경시적으로 조사하고자 150마리의 2일령 SPF 병아리 (Drkalb-Warren, Sex-Sal-Link)에 닭와포자충의 오오시스트 $5{\;}{\times}{\;}10^5$를 한 번에 경구투여하였타. 분변 속의 오오시스트 배설양상은 정상적이었으며. 파브리시우스낭 지수는 전 실험기간에 걸쳐 거의 변동이 없얹다 많은 수의 원충체가 접종 후 4-16일에 이 낭상피의 미세융또 가장자리에서 관찰되었으며 많은 수의 비만세포가 출현한 다음 원충체가 급격하게 소실하염다. 원충체의 분포상황과 상피 및 인접점막 고유층의 위호산구 침윤은 일치하였다. 이 병소는 상피. 인접 점막고유층의 위호산구 침율과 점만상피 증식을 동반한 미만성 만성 표재성 화농성 파브리시우스낭영의 병리조직학적 소견이었다 이러한 파브리시우스낭염은 면역억제를 유발할 건으로 생각된다.

• 대한수의학회지
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• 제45권4호
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• pp.545-552
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• 2005

The major protocol features of the rodent uterotrophic assay have been evaluated using a range of reference chemicals. The protocol variables considered include the selection of the test species and route of chemical administration, the age of the test animals, the maintenance diet used, and the specificity of the assay for estrogens. The rodents were ovariectomized under general anesthesia via bilateral flank incisions and randomly assigned to groups of 5 animals. Chemicals were DEHP, DBP, BPA and NP, were injected sc once daily with combinations of chemicals treatments for 3 days. In the results, the reported estrogenic chemicals DEHP and DBP were both negative in the single dose treatments. But, in the combinations of chemicals treatments, DEHP and DBP increased in bud number of mammary gland. Treatment of ovariectomized mice with combinations of other chemicals resulted in uterine and vaginal hyperplasia. The additive estrogenic effects were seen with the combinations of $17{\beta}$-Bestradiol and DBP treatment. the competitive estrogenic effects were seen with the combinations of $17{\beta}$-Bestradiol and nonylphenol, $17{\beta}$-Bestradiol and bisphenol-A treatments. These results offers a sysmatic and mechanistically informative approach to assessing estrogenicity. it provides a useful profile of activity using a reasonable amount of resources and is compatible with the study of individual chemicals as well as the investigation of interactions among combinations of chemicals. The results described illustrate the intrinsic complexity of evaluating chemicals for estrogenic activities and conform the need for rigorous attention to experimental design and criteria for assessing estrogenic activity.

• 대한수의학회지
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• 제53권1호
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• pp.29-35
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• 2013

To develop a live vaccine candidate using an attenuated strain of Salmonella Typhimurium (ST), biochemical properties, plasmid profile, PFGE patterns and pathogenic analysis of the ST isolate were carried out after sequential passage of the ST isolate in porcine neutrophils. By the passage, the ability of the neutrophil-adapted isolate to utilize d-xylose was lost, while the ability of the strain to ferment trehalose was delayed after 2 or more days of the culture. Also, changes including deletion of the gene fragments were observed in PFGE analysis of the neutrophil-adapted isolates. Two plasmids, 105kb and 50kb, were cured in the strain passaged over 15 times in porcine neutrophils. The 50% of lethal dose ($LD_{50}$) of the parent strain was changed from $1{\times}10^5\;LD_{50}$ to $6{\times}10^6\;LD_{50}$ by the passage in intraperitoneal injection of the strains into mice. These results suggested that bacterial genotypic and phenotypic responses might be globally altered depending on the inside environment of neutrophils.

• Journal of Pharmaceutical Investigation
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• 제39권5호
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• pp.359-366
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• 2009

In this study, paclitaxel-loaded lipid nanosuspension (PxLN) was prepared and the in vivo profiles after intravenous administration in rats were investigated. We compared the manufacturing processes depending on the temperature: PxLN-H for a hot homogenization process and PxLN-C for solidification of lipid-drug mixtures by liquid nitrogen. Both formulations showed submicron size distribution and the similar drug loading efficiency of about 70%. In vitro release of PxLNs and Taxol$^{(R)}$ performed by a dialysis diffusion method showed similar pattern for PxLN-H and Taxol$^{(R)}$, but the reduced release profile for PxLN-C. PxLN or Taxol$^{(R)}$ was intravenously administered to the rats at a dose of 5 mg/kg as paclitaxel. The drug in blood samples were assayed by the HPLC/MS/MS method. The AUC$_t$ of PxLN-H was 3.4-fold greater than that of Taxol$^{(R)}$. PxLN-H gave higher biodistribution in all tissues than did Taxol$^{(R)}$. In addition, it maintained the higher drug concentration for 12 h. This lipid nanosuspension might be a promising candidate for an alternative formulation for the parenteral delivery of poorly water-soluble paclitaxel.

• 생명과학회지
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• 제8권6호
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• pp.681-686
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• 1998

이상의 결과로부터 spin lavel의 영향은 IASL, MSL은 이완상태 myosin head의 규칙적인 나선 배열은 흐트러진다. 특히 IASL은 효과가 크다. 적도반사의 변화로부터 myosin head는 spin label하는 것에 의해 actin filament 근방에 이동해 있다는 것을 알 수 있었다. 215 $\AA$ 반사의 감소는 spin lavel에 의한 myosin의 143 $\AA$주기성을 더욱 강하게 해 준다. 143 $\AA$, 72 $\AA$의 거동은 filament축으로부터 투영한 구조를 반영하기 때문에 IASL에는 143 $\AA$ 주기의 밀도분포가 완만하게 되어 있다는 것을 나타내고, MSL에는 143 $\AA$ 분포가 올라와 있다는 것을 나타낸다. actin 반사변화에서 MSL의 actin반사의 증가는 이동한 myosin head가 어떤 actin과 결합하였거나, spin lavel의 영향으로 actin의 구조가 변화되었다. 한편, IASL은 actin반사를 감소 시키기 때문에 myosin head의 결합을 하지 않았다. 결론적으로, 이것은 actin의 SH기에도 spin label되어 actin의 나선 구조가 크게 흐트러짐을 알 수 있었다