• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1367-1370
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• 2015

Diagnosis of cholangiocarcinoma (CCA) is difficult when patients do not show jaundice. The aim of this study was to examine the feasibility of using the total serum bile acid (TSBA) level as an aid for the diagnosis of CCA in patients without jaundice. For this purpose, TSBA of the following groups were measured using a Beckman Synchron CX4 clinical chemistry analyzer: 60 cases of CCA with total serum bilirubin ${\leq}2mg/dL$ (low total bilirubin group, LTB); 32 cases of CCA with total serum bilirubin >2 mg/dL (high total bilirubin group, HTB); and 115 healthy controls. Liver function parameters such as serum cholesterol, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were also examined. The results showed that the TSBA of both LTB and HTB groups of the CCA patients were significantly higher than that of the healthy controls. Also, significant correlation was observed between TSBA and total bilirubin levels in the HTB group of CCA patients. However, no such correlation was seen in the LTB group. The cut-off value of TSBA was determined for the LTB group of CCA patients using the receiver operating characteristic curve analysis, and it was $6.05{\mu}mol/L$ with the sensitivity and specificity of 46.7% and 84.4%, respectively. In addition, the ALP level was correlated well with the TSBA level and ALP in HTB group was significantly higher than that of LTB group. Moreover, the combination of high TSBA and high ALP levels gave higher specificity up to 97.4%. TSBA might be useful for the diagnosis of CCA patients without jaundice.

• 대한한의학회지
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• 제26권3호
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• pp.228-238
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• 2005

Objectives : We conducted a randomized, double-blinded clinical trial to assess the anti-hypertensive effect of Ginseng and to know the difference of the effect according to it's growing districts md species by 24-hour ambulatory blood pressure measurement (ABPM). Methods : We allocated 96 hypertensive patients enrolled in this trial to Korean ginseng(KG), American ginseng (AG), Chinese ginseng (CG), and Korean red ginseng (KRG) groups by randomization. Each subject was administered 4.5mg/day of encapsulated ginseng for 4 weeks. We assessed anti-hypertensive effect, blood pressure variability using ABPM and toxicity by blood chemistry before and after treatment. We also evaluated changes of symptoms due to hypertension and adverse effect in all groups at the first visit, 2 weeks later and 4 weeks later. Results : Blood pressure after treatments showed significant decrease of systolic blood pressure (sBP) in the CG-group (p<0,05) and diastolic blood pressure (dBP) in the KRG-group (p<0.05). However, there were no significant changes of sBP (or dBP) after treatment in the other groups and no significant difference in changes of BP between before and after treatment among the 4 groups. Blood pressure variability in the CG-group showed significant decrease after treatment but not in the KRG-group. Symptoms such as headache or neck stiffness and heating sensation due to hypertension improved significantly in all groups, especially in the KRG-group. A3l patients had no adverse effect after treatment and there was no liver or kidney toxicity. Conclusions : CG and KRG seem to have anti-hypertensive effects, but there was no significantly different effect depending on growing district and species of Ginseng.

• 대한한의학방제학회지
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• 제24권2호
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• pp.80-99
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• 2016

Objectives : Instrumental chemical analysis was utilized to investigate the effect of Add-Omit-Saenghyeoryunbu-eum(AO-SHU) on diabetic treatment. One of the most exciting, yet also controversial, arguments is the safety and biological mechanisms of the natural medicine on human body. Therefore, the aim of this study is to provide a better understanding on bioactive chemical components, hazards of heavy metal contamination and biological mechanism of the diabetic medicine composed of 12 different natural herbs. Methods : To study bioactive compound and metallic component in the diabetic medicine in detail, LC-MS/MS (Liquid Chromatography-Mass/Mass), GC (Gas Chromatography) and ICP (Inductively Coupled Plasma) were utilized to characterize the extract of the diabetic medicine and the result was compared with 18 marker substances selected from literature survey. In addition, in vitro assay experiments including GPR 119 activity and human DGAT-1 inhibition, and OGTT (Oral Glucose Tolerance Test) were performed to verify the effectiveness of this medicine on diabetic treatment. Results : Out of 18 marker substances, 9 bioactive compounds were identified from LC-MS/MS analysis which include Citruline, Catalpol, Berberine, Ginsenoside Rb1, Ginsenoside Rg1, Oleanolic acid, β-Sitosterol, Mangiferin, and Schizandrin. ICP study on 245 residual pesticides revealed that 239 species were not detected but 6 species, Dimethomorph, Trifloxystrobin, Pyraclostrobin, Isoprocarb, Carbaryl and Flubendiamide, while the amounts are trace levels, below permitted concentrations. The biological activity was observed in vitro assay and Oral Glucose Tolerance Test(OGTT), which are consistent with a preliminary clinical test result, a drop in blood sugar level after taking this herbal medicine. Conclusions : Instrumental chemical analysis using LC-MS/MS, GC, and ICP was conducted successfully to identify bioactive compounds in AO-SHU for the treatment of diabetes, finding 9 bioactive compounds. Furthermore, in vitro assay experiments and OGTT show that AO-SHU has its biological activities, which imply that it can be a candidate for the future diabetes remedy.

• 생약학회지
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• 제46권1호
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• pp.44-51
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• 2015

The objective of this study is to characterize a toxicity of Polygalae Radix (PR) in F344 rats and to find a dose levels for the 13 weeks toxicity study. PR is well known as medicinal herb in many Asian countries for treatment of expectorant, tonic, tranquillizer, antipsychotic agent and functional diet for improving memory. However, there is insufficient background information on toxicological evaluation of PR extract to support its safe use. Therefore, we conducted toxicological evaluation of this drug in compliance with OECD and KFDA guideline in this study. The extract of PR was administered orally to F344 rats at dose levels of 0, 500, 1000, 2000, 3500 and 5000 mg/kg/day for 2 weeks. Each group was composed to five male and five female rats. In the result, there were no treatment PR-related adverse changes in food consumption, hematology, clinical chemistry, urinalysis, gross finding at necropsy, organ weight examination. Four males at 5000 mg/kg/day were found dead during the treatment period. These animals showed salivation. The cause of death is still under investigation. The animals treated at 500, 1000, 2000, 3500 and 5000 mg/kg/day showed salivation and all animals at 5000 mg/kg/day exhibited lower body weight and cumulative weight gain in compared to those of control animals. Therefore, we recommend that a dose group of 3500 mg/kg/day is a highest treatment group in 13-week exposure study.

• 한국수의병리학회지
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• 제3권2호
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• pp.87-91
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• 1999

The present study was undertaken to compare the variation on serum biochemical values by storage in the rats. Sera were prepared from 30 Sprague-Dawley rats of each sex. 5 aliquots from each serum were placed in a -80$^{\circ}C$ freezer with the exception of I aliquots which was analyzed immediately. The analysis was performed on the following months; 1, 2, 3, 6, and 12 months after freezing. The parameters measured) were aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP), blood urea nitrogen(BUN) creatinine(CRE), glucose(GLU), total cholesterol(TCHO), triglyceride (TG), total protein(TP), albumin(ALB), total bilirubin(TBIL), calcium(Ca$\^$＋＋/), inorganic phosphorus(IP), creatine kinase (CK), phospholipid(PL), albumin-globulin ratio(A/G), sodium(Na$\^$＋/), potassium(K$\^$＋/), and chloride(Cl$\^$－/) The statistical analysis with Repeated Measures ANOVA, did not show statistical significance in the parameters of AST, ALT, BUN, TG, CK, A/G, Na$\^$＋/ of 1 month freezed sera, in those of AST, TG, CK, K$\^$＋/) of 2 month freezed sera, in those of AST, ALT, BUN, CRE, TCHO, TP, TBIL, CK, PL, Na$\^$＋/), K$\^$＋/), Ct on month fteezed sera, in those of Cl$\^$－/ of 6 month fteezed sera, and in those of ALT, TG, ALB of 12 month freezed sera in male SD rats. On the other hand, it did not show statistical significance in the parameters of AST, ALT, ALP, BUN, GLU, TCHO, TG, TBIL, CK, PL, A/G, Na$\^$＋/ of 1 month freezed sera, in those of AST, TCHO of 2 month freezed sera, in those of AST, BUN, CRE, TCHO, TP, TBIL, CK, PL of 3 month freezed sera, in those of TCHO, IP, PL of 6 month freezed sera, and in those of ALB of 12 month freezed sera in female SD rats. On the basis of the results, although there are some statistical variations in the biochemical values of the sera, it is suggested that if sera are analysed at the same time before 12 months storage in a －80 $^{\circ}C$ freezer, the storing time does not affect the biochemical evaluation of the sera in SD rats.

• Journal of Magnetics
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• 제16권4호
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• pp.350-362
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• 2011

The principal objective of this study was to develop a scanning technique that helps patients reduce their anxiety and relax their physical tension in the MRI system. The study targeted 10 healthy persons with no medical history of anxiety disorder in the past and with no current clinically diagnosed anxiety disorder, as well as 10 patients who were currently experiencing an anxiety disorder during the MRI scanning. The focusing board assembly was self-manufactured to conduct a clinical experiment via MRI scans. As a method to confirm the efficacy of the experiment, the bio meter was used to measure brainwaves from the study targets that were divided into the normal person group (A), who felt no anxiety in the MRI system and the experimental group, (B) who did experience anxiety in the MRI system. The two groups were compared between the cases in which the focusing board assembly was used and not used after measurements were conducted using the model MRI system and the bio meter. According to the comparison and analysis results, low measurements of the ${\alpha}$ wave indicate highly effective relaxation of tension. In the normal person group, the ${\alpha}$ wave measurement showed almost no difference between cases in which the focusing board assembly was used and cases in which it was not used. In the experimental group, the $\acute{a}$ wave measurements were lower in cases in which the focusing board assembly was used than in cases in which the focusing board assembly was not used; this was indicative of a profound relaxation effect.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.655-663
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• 2002

Liver fibrosis is a prepathological state wherein damaged liver tissues in chronic liver diseases, such as hepatitis, are not repaired to normal tissues, but converted to fibrous tissue. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a cancer chemopreventive agent, is effective against a wide variety of chemical carcinogens. Recently, we reported that oltipraz inhibits liver fibrogenesis (Kang et al., 2002). In the present study, the effects of oltipraz in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDb) on dimethylnitrosamine (DMN)-induced liver fibrogenesis were assessed in rats. Oltipraz (30 mg/kg body weight, po, 3 times per week for 4 weeks) was found to inhibit the increases in plasma ALT, AST and bilirubin by DMN, whereas DDB (30 mg/kg body weight, po, 3 times per week for 4 weeks) attenuated the increases in the plasma ALT and bilirubin. The lowered plasma protein and albumin contents in DMN-treated rats were completely restored by oltipraz, but not by DDB. DDB decreases liver cell injury and inflammation through inhibition of nuclear factor-kB. DMN increased the accumulation of liver collagen, as indicated by the increase in the 4-hydroxyproline content in liver homogenates, which was reduced by treatment with oltipraz, but not by DDB. Given the differential effect between oltipraz and DDB, the potential enhancement of antifibrotic efficacy by the drugs was assessed in the animal model. Despite the minimal effect of DDB on DMN-induced fibrogenesis, DDB (5-25 mg/kg), administered together with oltipraz (25-5 mg/kg), showed an additive protective effect against hepatotoxicity and fibrosis induced by DMN, which was shown by the blood chemistry parameters and histopathological analysis. The adequate composition ratio of oltipraz to DDB was 5:1. These results provide information on the pharmaceutical composition, comprising of oltipraz and DDB as the active components, for the treatment and/or prevention of liver fibrosis and cirrhosis.

• 대한화학회지
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• 제54권4호
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• pp.451-459
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• 2010

세포내의 중금속이온의 형광검출은 유기분자화학과 세포생물학분야에서 높은 관심을 갖는다. 이 연구는 형광화학센서(FS)를 이용한 Hg$^{2+}$ 과 Zn$^{2+}$의 세포 내 검출을 목적으로 하였다. FS는 약한 형광을 나타내지만 Zn$^{2+}$와 결합 시에는 강한 방출 형광은 낸다. 2FS/Zn$^{2+}$의 형광증가는 FS-Hg$^{2+}$결합의 형성할 때 Hg$^{2+}$ 1당량만 추가에도 완전한 형광감소를 나타낼 수 있었다. 네가지의 세포주(LLC-MK2, Hela, HT29 and AMC-HN3)는 공촛점 현미경에 대한 형광이미지를 위하여 사용하였다. 세포생존능은 LLC-MK2 세포주에 FS, Zn$^{2+}$, FS-Zn$^{2+}$, Hg$^{2+}$의 처리 후에 평가하였다. FS의 세포독성능은 80%이상의 생존능을 보였다. 본 연구에서는 FS가 살아있는 세포내의 Hg$^{2+}$과 Zn$^{2+}$의 선택적 이미지를 검출할 수 있음을 보여주었다.

• 한국자원식물학회지
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• 제24권2호
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• pp.236-242
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• 2011

제주산 녹차 및 발효 정도를 20%, 50%, 80%로 달리한 3종류의 발효차를 $90^{\circ}C$ 열수에 추출하여 추출물의 항산화능, 지질과산화 억제능 그리고 혈관내피세포(CPAE)를 이용하여 산화스트레스에 대한 세포 보호효과를 조사하였다. 녹차나 다른 발효차에 비해 20% 발효차에서 항산화능을 평가하는 DPPH 소거능이 가장 우수한 것으로 나타났다. 20% 발효차의 80 ${\mu}g/mL$ 처리 시 50 ${\mu}M$ 농도의 EGCG 처리와 거의 유사한 free radical 소거율을 보였다. 녹차와 3종류의 발효차 모두 LDL 산화를 억제하여 우수한 지질과 산화 억제능을 보였으나 특히 저농도인 40 ${\mu}g/mL$ 처리 시에 녹차와 20% 발효차의 경우 다른 발효차에 비해 25~30% 정도 더 LDL의 산화가 억제 되어 50 ${\mu}M$/mL EGCG 처리 시와 거의 동일한 수준의 지질과산화 억제 효과를 보였다. CPAE 세포에 녹차 및 3종류의 발효차 추출물을 처리한 실험에서 전혀 추출물을 처리하지 않은 세포에 비해 세포활성이 40~60% 증가하였다. 특히 세포에 1 mM 과산화수소를 처리하여 산화스트레스를 유발한 실험에서 녹차 및 발효차 추출물의 처리가 세포의 산화스트레스에 대한 보호효과를 나타내는 것을 알 수 있었다. 이상의 결과들은 녹차 및 발효차 추출물이 세포 내 free radical을 제거함으로써 산화스트레스에 대한 세포 보호효과에 중요한 기능 중의 하나로 작용한 것과 20% 발효차가 다른 발효차에 비해 우수한 항산화기능을 나타낸다는 것을 보여주었다.

• Journal of Pharmaceutical Investigation
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• 제30권3호
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• pp.191-199
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• 2000

Genomics is providing targets faster than we can validate them and combinatorial chemistry is providing new chemical entities faster than we can screen them. Historically, the drug discovery cascade has been established as a sequential process initiated with a potency screening against a selected biological target. In this sequential process, pharmacokinetics was often regarded as a low-throughput activity. Typically, limited pharmacokinetics studies would be conducted prior to acceptance of a compound for safety evaluation and, as a result, compounds often failed to reach a clinical testing due to unfavorable pharmacokinetic characteristics. A new paradigm in drug discovery has emerged in which the entire sample collection is rapidly screened using robotized high-throughput assays at the outset of the program. Higher-throughput pharmacokinetics (HTPK) is being achieved through introduction of new techniques, including automation for sample preparation and new experimental approaches. A number of in vitro and in vivo methods are being developed for the HTPK. In vitro studies, in which many cell lines are used to screen absorption and metabolism, are generally faster than in vivo screening, and, in this sense, in vitro screening is often considered as a real HTPK. Despite the elegance of the in vitro models, however, in vivo screenings are always essential for the final confirmation. Among these in vivo methods, cassette dosing technique, is believed the methods that is applicable in the screening of pharmacokinetics of many compounds at a time. The widespread use of liquid chromatography (LC) interfaced to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) allowed the feasibility of the cassette dosing technique. Another approach to increase the throughput of in vivo screening of pharmacokinetics is to reduce the number of sample analysis. Two common approaches are used for this purpose. First, samples from identical study designs but that contain different drug candidate can be pooled to produce single set of samples, thus, reducing sample to be analyzed. Second, for a single test compound, serial plasma samples can be pooled to produce a single composite sample for analysis. In this review, we validated the issue whether the second method can be applied to practical screening of in vivo pharmacokinetics using data from seven of our previous bioequivalence studies. For a given drug, equally spaced serial plasma samples were pooled to achieve a 'Pooled Concentration' for the drug. An area under the plasma drug concentration-time curve (AUC) was then calculated theoretically using the pooled concentration and the predicted AUC value was statistically compared with the traditionally calculated AUC value. The comparison revealed that the sample pooling method generated reasonably accurate AUC values when compared with those obtained by the traditional approach. It is especially noteworthy that the accuracy was obtained by the analysis of only one sample instead of analyses of a number of samples that necessitates a significant man-power and time. Thus, we propose the sample pooling method as an alternative to in vivo pharmacokinetic approach in the selection potential lead(s) from combinatorial libraries.