• Radiation Oncology Journal
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• 제11권1호
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• pp.119-126
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• 1993

From 1988 to 1991, nineteen patients with unresectable localized pancreatic carcinoma were treated with radiotherapy and/or hyperthermia or in combination with chemotherapy. Radiation dose of 4500-5000 cGy with or without additional 500-1000 cGy was administered over 5 to 6 weeks to the pancreatic tumor area using 10 MV linear accelerator. Five of 19 patients were given chemotherapy, either neoadjuvant or maintenance setting with FAM regimen (5-FU, adriamycin and mitomycin C), which was repeated every 4 weeks for one year or until progression. Symptomatic palliation was achieved in 17 among 19 patients ($89{\%}$) and objective response (complete or partial response in CT finding) was achieved in 5 among 11 patients ($45{\%}$). The median survival time was 9 months and one-year survival rate, $32{\%}$. Local-regional failure was documented in 10 among 13 patients ($77{\%}$) and distant failures were found in the liver (3 patients) and carcinomatosis (2 patients). Prognostic significance of various factors such as age, sex, performance status, tumor location, stage, etc. were assessed. Any factors did not have the prognostic significance in univariate analysis. Treatment was well tolerated in most of the patients with only mild to moderate toxicity.

• Biomolecules & Therapeutics
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• 제21권1호
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• pp.84-88
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• 2013

High risk of cardiovascular diseases caused by existing PPAR-${\gamma}$ agonists such as rosiglitazone and pioglitazone has been recently reported. CKD-501 is a novel selective PPAR-${\gamma}$ agonist as a potential target to reduce cardiovascular risk in non-insulin dependent diabetes mellitus (NIDDM). In this study, We investigated potential cardiotoxicity of CKD-501 and compared its toxicity with that of rosiglitazone or pioglitazone using db/db mice. After 12-week repeated administration of CKD-501 at doses of 3, 10 and 30 mg/kg/day or rosiglitazone at doses of 10 and 30 mg/kg/day or pioglitazone at doses of 200 and 540 mg/kg/day, animals were sacrificed for investigation of potential toxicities. Diameters of left ventricles and areas of cardiomyocytes were measured. And lipid accumulation and apoptosis in heart muscle were examined by oil red O staining and TUNEL staining, respectively. Diameters of left ventricles were significantly increased in high dose treatment group of pioglitazone compared to control (p<0.05), while other groups showed a tendency for an increase. All test articles induced significantly the increase of area of cardiomyocytes in heart compared to control (p<0.01), in regular order as pioglitazone > CKD-501 ${\geq}$ rosiglitazone. However, lipid accumulation and apoptotic changes in heart were not observed in all dosing groups. Taken together, the myocardial cell hypertrophy of CKD-501 are relatively lower than that of pioglitazone and similar to rosiglitazone. And it is suggested that the myocardial cell hypertrophy of CKD-501 are less adverse in clinical use for the management of the NIDDM.

• Journal of Chest Surgery
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• 제30권12호
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• pp.1205-1213
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• 1997

가톨릭대학교 의과대학 부속 성바오로 병원에서 1996년 1월부터 7월까지 개심술시 경식도심초음파를 이용하여 수술 중 관찰한 61명의 증례를 분석하여 다음과 같은 결과를 얻었다. 61명의 환자 중 질병 분류는 심장 판막 질환 25명, 관상동맥 질환 22명, 선천성 심질환 13명, 심장 판막 질환과 관상동맥 질환이 병발한 경우가 1명 이었다. 1. 경식도심초음파를 이용하여 선천성 심질환 1예(심실중격결손증 재수술)와 대동맥 판막 치환술을 시행한 환자 1예에서 일차 심정지에 의한 수술 후 잔존 단락과 판막 주위 누출이 확인되어 재심정지를 유도하여 수술을 완료하였다 2. 공기색전증의 발생을 전 예에서 방지할 수 있었다. 3. 경식도심초음파로 측정한 심박출량과 온도희석법으로 측정한 심박출량은 통계학적으로 의미있는 상관관계를 보여 경식도 초음파를 이용한 심박출량 감시가 의미 있음을 시사하였다(Linear regression analysis, p<0.001). 4. 관상동맥우회로술을 시행한 23명의 환자에서 수술 중 경식도 초음파도상 이상 벽운동을 보이는 분절의 도부타민 투여 전후와 관상동맥우회로술 후의 반응을 비교 관찰하였다. 저 용량 도부타민 검사는 통계적으 \ulcorner유의하였다(민감도 76%, 특이도 94.7%, 양성 예측율 95%, 음성 예측율 75%).

• Radiation Oncology Journal
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• 제13권2호
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• pp.121-128
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• 1995

Purpose: The enhanced cytotoxic effect of combined treatment of hyper-thermia and chemotherapy by increasing intracellular acidity with HMA was investigated. Materials and Methods: FSall tumor cells were injected on the hindlegs of female $C_3H$ mice. When the tumor volume reached about 200mm3, experiments were performed on the groups classified as follows: Group I :Control, Group II : Melphalan alone (2.5mg/kg, 5mg/kg, 10mg/kg, 15mg/kg), Group III : Heat alone $(42.5^{\cdot}C$ for 1 hour) Group IV : Melphalan + Heat $(42.5^{\cdot}C$ for 1 hour), Group V : HMA(10mg/kg) + Melphalan(5.0mg/kg) + Heat$(42.5^{\cdot}C$ for 1hour). Each group included 8-12 mice on each experiment HMA (3-amino-6-chloro-5-(1-homopiperidyl )-N-(diaminomethylene) -c-pyrazinecarboxamide), an analog of amiloride which increases intracellular pH(pHi) was dissolved in dimethyl sulfoxide (DMS) and injected into the tumor-bearing mice through the tail vein. 10mg/kg of HMA and each dose of melphalan were injected into peritoneum of the tumor-bearing mice 30 minutes before heating. Tumor growth delay was calculated when the tumor volme reached at $1500mm^3$ Excision assay was performed on each group and repeated 2-4 times. Results : Tumor growth delay of each experimental groups at $1500mm^3$ were 9, 10, 13 and 19 days respectively. In vivo-in vitro excision assay using FSall tumor cells, the cytotoxicity of each experimental groups was $1.2{\times}10^7,\;1{\times}10^7,\;6{\times}10^6,\;1.7{\times}10^6\;and\;1{\times}10^5$ clonogenic cells/gm respectively When HMA was added to the combined treatment of heat and .chemotherapy, the tumor growth was delayed more than combined treatment without HMA i.e., 6 days tumor growth delay at $1500mm^3$ of tumor volume. Conclusion: The combined effect of cytotoxicity by heat and chemotherapy can be much more enhanced by HMA.

• Journal of Ginseng Research
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• 제42권3호
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• pp.370-378
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• 2018

Background: Ginseng has been the subject of many experimental and clinical studies to uncover the diverse biological activities of its constituent compounds. It is a traditional medicine that has been used for its immunostimulatory, antithrombotic, antioxidative, anti-inflammatory, and anticancer effects. Ginseng may interact with concomitant medications and alter metabolism and/or drug transport, which may alter the known efficacy and safety of a drug; thus, the role of ginseng may be controversial when taken with other medications. Methods: We extensively assessed the effects of Korean Red Ginseng (KRG) in rats on the expression of enzymes responsible for drug metabolism [cytochrome p450 (CYP)] and transporters [multiple drug resistance (MDR) and organic anion transporter (OAT)] in vitro and on the pharmacokinetics of two probe drugs, midazolam and fexofenadine, after a 2-wk repeated administration of KRG at different doses. Results: The results showed that 30 mg/kg KRG significantly increased the expression level of CYP3A11 protein in the liver and 100 mg/kg KRG increased both the mRNA and protein expression of OAT1 in the kidney. Additionally, KRG significantly increased the mRNA and protein expression of OAT1, OAT3, and MDR1 in the liver. Although there were no significant changes in the metabolism of midazolam to its major metabolite, 1'-hydroxymidazolam, KRG significantly decreased the systemic exposure of fexofenadine in a dose-dependent manner. Conclusion: Because KRG is used as a health supplement, there is a risk of KRG overdose; thus, a clinical trial of high doses would be useful. The use of KRG in combination with P-glycoprotein substrate drugs should also be carefully monitored.

• 약학회지
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• 제43권1호
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• pp.33-41
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• 1999

Whereas as selective inhibitor of monoamine oxidase type B, ${\ell}-deprenyl$ (selegiline), is now widely used in the treatment of Parkinson's disease, the precise action mechanism of the drug remains elusive. In this study, to investigate protective effect of ${\ell}-deprenyl$ against the dopamine depletion induced by 6-hydroxydopamine (6-OHDA), the changes in tissue contents of dopamine, serotonine (5-HT) and their metabolites by ${\ell}-deprenyl$ were examined in intact and 6-OHDA-lesioned rat brain. In intact rats, a single intraperitoneal (i.p.) administration of ${\ell}-deprenyl$ showed a no change in striatal dopamine and its metabolites at low concentrations (0.25 and 1 mg/kg), but significantly inhibited dopamine metabolism at a higher concentration (10 mg/kg). The repeated administration of ${\ell}-deprenyl$ (0.25 and 1 mg/kg, i.p., for 21 consecutive days) reduced the contents of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in dose-dependent manners without changes in dopamine content. Bilateral intracerebroventricular (i.c.v) infusion of 6-OHDA ($100{\;}\mu\textrm{g}/10{\;}{\mu}{\ell}/hemisphere$) depleted dopamine in striatum and septum by 81% and 90% respectively. When rats were pretreated with ${\ell}-deprenyl$ before 6-OHDA administration, the striatal and septal dopamine levels were significantly increased by about 3.0-fold and 3.4-fold, respectively, compared to the untreated 6-OHDA-lesioned rat. Pretreatment of ${\ell}-deprenyl$ also significantly enhanced the dopmaine metabolites, DOPAC, HVA and 3-methoxytyramine, in the striatum, and DOPAC in the septum. These results indicate that a ${\ell}-deprenyl$ pretreatment prevents 6-OHDA-induced depletion of striatal dopamine and its metabolites.

• 대한임상독성학회지
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• 제15권2호
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• pp.148-151
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• 2017

Methemoglobinemia is a condition in which the iron portion of hemoglobin, which binds to oxygen, is oxidized to produce methemoglobin, which increases blood concentration. There are many causes of methemoglobinemia, the most common being food, drugs, and chemicals. A 75-year-old male patient who had taken an herbicide did not notice any nonspecific symptoms. However, after 4 hours, his methemoglobin levels increased to 17.1%, while after 7 hours it increased to 26.5%, at which time intravenous administration of methylene blue 1 mg/kg (an antidote) was started. After a total of five doses of methylene blue at 1 mg/kg due to reactive methemoglobinemia for about 36 hours, the methemoglobin levels increased to 23.7%. Because no more methylene blue could be administered, 10 g of ascorbic acid (vitamin C) was administered intravenously. After 82 hours, ascorbic acid 10 g was administered six times for repeated reactive methemoglobinemia. No additional reactive methemoglobinemia was observed. The ventilator and endotracheal tube were successfully removed on day 5 after admission.

• Toxicological Research
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• 제33권4호
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• pp.283-290
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• 2017

The host immune system is the first line of host defense, consisting mainly of innate and adaptive immunity. Immunity must be maintained, orchestrated, and harmonized, since overactivation of immune responses can lead to inflammation and autoimmune diseases, while immune deficiency can lead to infectious diseases. We investigated the regulation of innate and adaptive immune cell activation by Artemisia capillaris and its components (ursolic acid, hyperoside, scopoletin, and scopolin). Macrophage phagocytic activity was determined using fluorescently labeled Escherichia coli, as an indicator of innate immune activation. Concanavalin A (ConA)- and lipopolysaccharide (LPS)-induced splenocyte proliferation was analyzed as surrogate markers for cellular and humoral adaptive immunity, respectively. Neither A. capillaris water extract (WAC) nor ethanol extract (EAC) greatly inhibited macrophage phagocytic activity. In contrast, WAC suppressed ConA- and LPS-induced proliferation of primary mouse splenocytes in a dose-dependent manner. Similarly, EAC inhibited ConA- and LPS-induced splenocyte proliferation. Oral administration of WAC in mice decreased ConA- and LPS-induced splenocyte proliferation, while that of EAC suppressed LPS-induced splenocyte proliferation. Repeated administration of WAC in mice inhibited ConA- and LPS-induced splenocyte proliferation. Ursolic acid, scopoletin, and scopolin reduced ConA- and LPS-induced primary mouse splenocyte proliferation, while hyperoside did not show such activity. These results indicate that A. capillaris and its components, ursolic acid, scopoletin, and scopolin, suppress ConA- and LPS-induced adaptive immune cell activation. The results suggest that A. capillaris is useful as a regulator of adaptive immunity for diseases involving excessive immune response activation.

• 생약학회지
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• 제36권3호통권142호
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• pp.201-204
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• 2005

The rhizome extract of Atractylodes japonica Koidzumi(Compositae) exhibited a particular inhibition on the proliferation of cultured human tumor cell lines, in vitro. Thus, the intensive phytichemical investigation of the MeOH extract of Atractylodes japonica have been conducted by the way of activity-guided purification. The repeated column chromatographic separation of the n-hexane soluble part of extract resulted in the isolation of four sesquiterpenes (1-4) and a polyacetylene component (5). Chemical structures of them were identified as atractylon (1), atractylenolide Ⅰ(2), atractylenolide Ⅲ(3), eudesma-4(15),7(11)-dien-8-one (4) and 1,3-diacetyl-atractylodiol (5) by spectroscopic means. Among the isolates, compound 2-4 were shown to give moderate inhibitory effect in a dose dependent manner on the proliferation of cultured human tumor cell lines such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT 15(colon), respectively.

• Food Science and Biotechnology
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• 제17권6호
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• pp.1214-1220
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• 2008

Secondary metabolites from the fruit body of Phellinus linteus were evaluated for their proliferative effect on human osteoblast-like cells. 3-[4,5-Dimethylthiazole-2-y1]-2,5-diphenyl-tetraxolium bromide (MTT) assay and alkaline phosphatase (ALP) activity assay were used to assess the effect those isolates on the human osteoblast-like cell line (Saos-2). Activity-guided fractionation led to the isolation of ALP-activating phenolic compounds through the extraction of P. linteus, solvent partitioning, and repeated silica gel and octadecyl silica gel (ODS) column chromatographic separations. From the result of spectroscopic data including nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR), the chemical structures of the compounds were determined as 4-(4-hydroxyphenyl)-3-buten-2-one(1), 2-(3',4'-dihydroxyphenyl)-1,3-benzodioxole-5-aldehyde (2), 4-(3,4-dihydroxyphenyl)-3-buten-2-one (3), 3,4-dihydroxybenzaldehyde (4), and protocatechuic acid methyl ester (5), respectively. This study reports the first isolation of compounds 1-3 and 5 from P. linteus. In addition, all phenolic compounds stimulated proliferation of the osteoblast-like cells and increased their ALP activity in a dose-dependent manner ($10^{-8}$ to $10^{-1}\;mg/mL$). The present data demonstrate that phenolic compounds in P. linteus stimulated mineralization in bone formation caused by osteoporosis. The bone-formation effect of P. linteus seems to be mediated, at least partly, by the stimulating effect of the phenolic compounds on the growth of osteoblasts.