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Drug research and development tend to hyperlipidemia (이상지질혈증과 치료제 연구개발 경향)

  • Seol, In-Chan
    • Journal of Haehwa Medicine
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    • v.18 no.2
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    • pp.1-12
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    • 2009
  • Most of the cholesterol is synthesized by liver in the body while about one of third is taken via dietary. The main functions of cholesterol is to protect membranes in cell surface, avoid the arterial bleeding by hypertension, and prolong the life of erythrocytes, and so on. However, overload of cholesterol leads to arteriosclerosis associated with leading death cause. Lack of physical activity, emotional and environmental stress, and low intake of protein or vitamin E induce the unbalance between HDL- and LDL-cholesterol so become a basis of ischemic disorders in heart, brain and elsewhere in the body. So far, four major classes of medications for hyperlipidemia are HMG-CoA reductase inhibitors (statins), bile acid sequestrants, nicotinic acid, and fibric acids. The statins can lower LDL and levels triglyceride, but may induce myopathy and an elevation of liver enzyme levels. The bile acid sequestrants lower LDL levels and raise HDL levels with no effect on triglyceride levels but side effects of gastrointestinal (GI) distress, constipation, and a decrease in the absorption of other drugs. Nicotinic acid and fibric acids lower LDL and triglyceride levels with showing flushing, hyperglycemia, hyperuricemia, GI distress, and hepatotoxicity dyspepsia, gallstones, myopathy, and unexplained noncardiac death as adverse effects. Above western drugs lower cholesterol by 15 to 30% while all have notable adverse effects. In traditional medicine, hyperlipidemia is regarded as retention of phlegm and fluid disease. Etiology and pathogenesis of hyperlipidemia is basically based on Spleen-Deficiency and Phlegm-Stagnation, accumulation and stasis of -heat, and Qi & blood stagnation induced by Phlegm-damp, water-dampness, and blood stasis. Thereby, strengthening Spleen and dissolving Phlegm, clearing away heat and diuresis, and supplementing Qi and activating blood circulation are commonly used therapeutic methods for hyperlipidemia. The traditional herbal medicine, have been used for patients with CVA, hypertension or hyperlipidemia in Oriental hospital or Oriental clinic. The lock and key theory is used to develop most of western medicine, however many diseases are caused by mixed factors in body-complex system. We expect that Oriental pharmacological theory could be newborn as a novel drug showing high advantage of blood levels of lipidsand QOL of performance without side effects.

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The Isolation of the Inhibitory Constitutents on Melanin Polymer Formation from the Leaves of Cercis chinensis (박태기나무의 잎으로부터 피부멜라닌 색소생성 억제성분의 분리)

  • Kim, So-Young;Kim, Jin-Joon;Jang, Tae-Soo;Chung, See-Ryun;Lee, Seung-Ho
    • Korean Journal of Pharmacognosy
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    • v.30 no.4
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    • pp.397-403
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    • 1999
  • Tyrosinase plays an important role in the process of melanin polymer biosynthesis. Therefore, the enzyme inhibitors have been of great concern as cosmetics to have skin-whitening effects on the local hyperpigmentation. During the search for new inhibitory compounds on melanin polymer biosynthesis from natural sources, MeOH extracts of 589 higher plants were tested for the inhibitory effect on tyrosinase activity by the muschroom tyrosinase assay in vitro. Among plants tested, the leaves of Cercis chinensis exhibited potent inhibitory effect on mushroom tyrosinase activity. Subsequently seven active compounds were isolated from the ethyl acetate soluble part of acetone extract of the leaves of C. chinensis by the activity guided fractionation monitoring the inhibitory effect on tyrosinase activity. Their chemical structures were identified as $kaempferol-3-0-{\alpha}-L-rhamnoside$, quercitrin, $myricetin-3-0-{\alpha}-L-rhamnoside$, myricetin-3-0-(2'-O-galloyl)- ${\alpha}$ -L-rhamopyranoside (desmanthin), (-)-epicatechin-3-0-gallate, (-)-epigallocatechin-3-0-gallate, and methyl gallate on the basis of the speculation of spectral data and chemical reaction. Among the flavonol rhamnosides, myricetin-3-0-(2'-O-galloyl)- -L-rhamnoside(desmanthin) showed most potent inhibitory effect on tyrosinase activity and the structure of B-ring in flavonol moiety was related to the activity. (-)-Epigallocatechin-3-O-gallate having pyrogallol group in flavan-3-ol moiety exhibited more potent inhibitory effect than (-)-epicatechin-3-0-gallate having catechol group in flavan-3-ol moiety on mushroom tyrosinase activity.

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Spontaneous Resolution of Chronic Subdural Hematoma : Close Observation as a Treatment Strategy

  • Kim, Hyung Chan;Ko, Jung Ho;Yoo, Dong Soo;Lee, Sang-Koo
    • Journal of Korean Neurosurgical Society
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    • v.59 no.6
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    • pp.628-636
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    • 2016
  • Objective : Chronic subdural hematoma (cSDH) is common condition in neurosurgical field. It is difficult to select the treatment modality between the surgical method and the conservative method when patients have no or mild symptoms. The purpose of this study is to provide a suggestion that the patients could be cured with conservative treatment modality. Methods : We enrolled 16 patients who had received conservative treatment for cSDH without special medications which could affect hematoma resolution such as mannitol, steroids, tranexamic acid and angiotensin converting enzyme inhibitors. The patients were classified according to the Markwalder's Grading Scale. Results : Among these 16 patients, 13 (81.3%) patients showed spontaneously resolved cSDH and 3 (18.7%) patients received surgery due to symptom aggravation and growing hematoma. They were categorized into two groups based on whether they were cured with conservative treatment or not. The first group was the spontaneous resolution group. The second group was the progression-surgery group. The mean hematoma volume in the spontaneous resolution group was 43.1 mL. The mean degree of midline shift in the spontaneous resolution group was 5.3 mm. The mean hematoma volume in the progression-surgery group was 62.0 mL. The mean degree of midline shift in the second group was 6 mm. Conclusion : We suggest that the treatment modality should be determined according to the patient's symptoms and clinical condition and close observation could be performed in patients who do not have any symptoms or in patients who have mild to moderate headache without neurological deterioration.

The Prevalence of Cardiovascular Disease Risk Factors and the Framingham Risk Score in Patients Undergoing Percutaneous Intervention Over the Last 17 Years by Gender: Time-trend Analysis From the Mayo Clinic PCI Registry

  • Lee, Moo-Sik;Flammer, Andreas J.;Kim, Hyun-Soo;Hong, Jee-Young;Li, Jing;Lennon, Ryan J.;Lerman, Amir
    • Journal of Preventive Medicine and Public Health
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    • v.47 no.4
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    • pp.216-229
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    • 2014
  • Objectives: This study aims to investigate trends of cardiovascular disease (CVD) risk factor profiles over 17 years in percutaneous coronary intervention (PCI) patients at the Mayo Clinic. Methods: We performed a time-trend analysis within the Mayo Clinic PCI Registry from 1994 to 2010. Results were the incidence and prevalence of CVD risk factors as estimate by the Framingham risk score. Results: Between 1994 and 2010, 25 519 patients underwent a PCI. During the time assessed, the mean age at PCI became older, but the gender distribution did not change. A significant trend towards higher body mass index and more prevalent hypercholesterolemia, hypertension, and diabetes was found over time. The prevalence of current smokers remained unchanged. The prevalence of ever-smokers decreased among males, but increased among females. However, overall CVD risk according to the Framingham risk score (FRS) and 10-year CVD risk significantly decreased. The use of most of medications elevated from 1994 to 2010, except for ${\beta}$-blockers and angiotensin converting enzyme inhibitors decreased after 2007 and 2006 in both baseline and discharge, respectively. Conclusions: Most of the major risk factors improved and the FRS and 10-year CVD risk declined in this population of PCI patients. However, obesity, history of hypercholesterolemia, hypertension, diabetes, and medication use increased substantially. Improvements to blood pressure and lipid profile management because of medication use may have influenced the positive trends.

Screening of Inhibitory Effect on Aldose Reductase of Vietnam Herbal Medicines (II) (베트남 약용식물 추출물의 알도즈 환원 효소 억제 효능 검색(II))

  • Lee, Yun-Mi;Kim, Jong-Min;Kim, Young-Sook;Jang, Dae-Sik;Kim, Joo-Hwan;Bae, Ki-Hwan;Kim, Jin-Sook
    • Korean Journal of Pharmacognosy
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    • v.39 no.4
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    • pp.324-329
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    • 2008
  • Aldose reductase (AR), the key enzyme in the polyol pathway, plays an important role in the pathogenesis of diabetic complications such as cataract formation. AR inhibitors (ARI) can prevent or reverse early abnormalities in diabetic complications. However, none of ARI has achieved worldwide use because of limited efficacy or undesirable side effects. Therefore, evaluating natural sources for ARI potential may lead to the development of safer and more effective agents against diabetic complications. 49 Vietnam herbal medicines have been investigated with an in vitro evaluation system using aldose reductase inhibitory activities. Of these, 7 herbal medicines, Artemisia annua (leaf, stem), Duranta repens (leaf, stem), Excoecaria cochinchinensis (aerial part), Flueggea virosa (leaf, stem), Khaya senegalensis (leaf), Polygonum orientale (aerial part), Toxicodendron succedanea (leaf, stem) exhibited a significant inhibitory activity against aldose reductase. Particularly, Duranta repens (leaf, stem) and Toxicodendron succedanea (leaf, stem) showed two times more potent inhibitory activity than the positive control, 3.3-tetramethyleneglutaric acid (TMG).

Itaconic and Fumaric Acid Production from Biomass Hydrolysates by Aspergillus Strains

  • Jimenez-Quero, A.;Pollet, E.;Zhao, M.;Marchioni, E.;Averous, L.;Phalip, V.
    • Journal of Microbiology and Biotechnology
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    • v.26 no.9
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    • pp.1557-1565
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    • 2016
  • Itaconic acid (IA) is a dicarboxylic acid included in the US Department of Energy's (DOE) 2004 list of the most promising chemical platforms derived from sugars. IA is produced industrially using liquid-state fermentation (LSF) by Aspergillus terreus with glucose as the carbon source. To utilize IA production in renewable resource-based biorefinery, the present study investigated the use of lignocellulosic biomass as a carbon source for LSF. We also investigated the production of fumaric acid (FA), which is also on the DOE's list. FA is a primary metabolite, whereas IA is a secondary metabolite and requires the enzyme cis-aconitate decarboxylase for its production. Two lignocellulosic biomasses (wheat bran and corn cobs) were tested for fungal fermentation. Liquid hydrolysates obtained after acid or enzymatic treatment were used in LSF. We show that each treatment resulted in different concentrations of sugars, metals, or inhibitors. Furthermore, different acid yields (IA and FA) were obtained depending on which of the four Aspergillus strains tested were employed. The maximum FA yield was obtained when A. terreus was used for LSF of corn cob hydrolysate (1.9% total glucose); whereas an IA yield of 0.14% was obtained by LSF of corn cob hydrolysates by A. oryzae.

Differential Expression of EGFR Protein by Immunohistochemical Staining Methods and the Relationship Between the Degree of EGFR Protein Expression and EGFR Gene Mutation (면역조직화학적 염색 방법에 따른 상피세포 성장 수용체 단백(EGFR)의 발현정도의 차이 및 EGFR의 발현정도와 EGFR 유전자의 돌연변이와의 상관관계에 대한 고찰)

  • Yoon, In-Sook;Kim, Keuk-Jun;Lee, Eun-Hwa;Seok, Sang-Hee;Kim, Sang-Hee;Kim, Hyun-Yong;Song, Ho-Jung;Lee, Tae-Jong
    • Korean Journal of Clinical Laboratory Science
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    • v.39 no.3
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    • pp.217-222
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    • 2007
  • In the last 5 years the Epidermal Growth Factor Receptor (EGFR) has emerged as one of the most important targets for drug development in oncology. Monoclonal antibodies targeting the external domain of EGFR have been shown to have clinical benefits in colorectal and head and neck cancer when combined with chemotherapy and/or radiation. Also the targeting of the epithelial growth factor receptor (EGFR) kinase domain using the closely related inhibitors gefitinib and erlotinib has generally been ineffective against solid tumors, many of which over express the receptor. We found that there were some differential expressions according to primary antibodies of the EGFR protein which being used as one of the histological tumor markers for non-small cell lung cancer (NSCLC). We also found that there are some differential expressions according to antibodies, the pH of the antigen retrieval (AR) buffer solutions and kinds of enzymes. There were some differential expressions according to the secondary antibodies and the detection systems. We analyzed the correlations between the immunohistochemical expressions of the EGFR protein and the gene mutations of the EGFR. The differences between automatic stainers and manual staining methods were also evaluated.

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Chemopreventive Effect of Vegetable or Fruit Extract Against Total Diesel Exhaust Particle Extract in NIH/3T3 Cells Using Alkaline Single Cell Gel Electrophoresis (총 디젤분진의 DNA 손상작용과 야채 및 과일추출물의 보호효과)

  • Heo Chan;Kim Nam-Yee;Heo Moon-Young
    • Environmental Analysis Health and Toxicology
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    • v.21 no.2 s.53
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    • pp.127-138
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    • 2006
  • In urban areas, diesel exhaust particles (DEP) are probably a major component of particulate matters, especially in Korea where drive many diesel vehicles. The aim of this study was to investigate genotoxic effects of DEP using single ceil gel electrophoresis. In order to evaluate the mechanisms of DEP genotoxicity, the rat microsome mediated and DNA repair enzyme treated comet assays together with conventional comet assay were performed. Total diesel particles (DEPT) was collected without site fractionation from diesel engine bus and dichloromethane extract was obtained. The organic extract of DEPT revealed DNA damage itself in NIH/3T3 cells. The level of DNA breaks plus oxidative DNA lesions and microsome mediated DNA damage was assessed by modified single cell gel eletrophoresis. DEPT was able to induce oxidative DNA damage as well as microsome mediated DNA damage. Vitamin C as an model antioxidant reduced DNA damage in endonuclase III treated comet assay. One of flavonoid, galangin as a CYP1A1 inhibitor. reduced DNA damage in the presence of S-9 mixture. $DEP_T$ is the sources of oxidative stress, but antioxidants can significantly reduce oxidative DNA dmage. And $DEP_T$ may contain indirect mutagens which can be inhibited by CYP1A1 inhibitors. The ethanol extracts of the mixed vegetables (BV) or the mixed fruits (BF) were evaluated for their in vitro antigenotoxic effects. BV and BF showed potent Inhibitory effects against DEPT induced DNA damage with oxidative DNA lesions and in the prescence of S-9 mixture. These results indicate that BV and BF could prevent cellular DNA damage by inhibiting oxidative stress and suppressing cytochrome P4501A1 in cell culture.

Antioxidative Effects of Extracts of Various Cultivars and Different Plant Parts of Eggplant (가지의 품종별, 부위별 추출물의 항산화 효과)

  • Beik, Kyung-Yean;Lee, Sang-Il;Kim, Jeong-Sook;Lee, Doo-Young;Oh, Seoung-Hee;Kim, Soon-Dong
    • Journal of the East Asian Society of Dietary Life
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    • v.19 no.2
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    • pp.195-201
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    • 2009
  • The antioxidative activities of two varieties of egg plant (Chunyang No 2: Dangaji, Jinju Janggaji: Janggaji) extracts were investigated. The total polyphenol contents of Dangaji peel hot water extract and the Janggaji flesh and fruit hot water extracts were higher than those of the other samples. However, the DPPH radical scavenging activities(electron donating activity) of Dangaji flesh-ethanol, peel-cold water, and fruit- ethanol extracts, as well as the Janggaji peel cold water extract, were higher than those of the other samples. Furthermore, the in vitro inhibitory effects of the Dangaji peel cold water and hot water extracts on rat hepatic xanthine oxidase were highest among the samples, and were exhibited in a dose dependant manners. Although there were marked changes in the xanthine oxidase Km values for xanthine as a substrate, the Vmax value changes by the addition of the Dangaji water extracts were minor compared with the control. This result suggests that Dangaji water extracts may regulate the activity of xanthine oxidase-via the inhibition of binding affinity between the enzyme and substrate. The present study provides experimental evidence that constituents of egg plant extracts may ameliorate reactive oxygen species(ROS)-induced oxidative stress via hepatic hepatic xanthine oxidase activity, but further studies to identify the active antioxidants and compounds and inhibitors of xanthine oxidase are required.

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Effect of Allium sativum on cytochrome P450 and possible drug interactions

  • Janil, Ashutosh;Mehta, Anita A
    • Advances in Traditional Medicine
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    • v.6 no.4
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    • pp.274-285
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    • 2006
  • Allium sativum (Family Amaryllidaceae or Liliaceae) is used worldwide for various clinical uses like hypertension, cholesterol lowering effect, antiplatelets and fibrinolytic activity etc. Due to these common house hold uses of Allium sativum, as a herbal supplements, and failure of patients to inform their physician of the over-the-counter supplements they consume leads to drugnutrient interactions with components in herbal supplements. Today these types of interactions between a herbal supplement and clinically prescribed drugs are an increasing concern. In vitro studies indicated that garlic constituents modulated various CYP (cytochrome P450) enzymes. CYP 3A4 is abundantly present in human liver and small intestine and contributes to the metabolism of more than 50% of commonly used drugs including nifedipine, cyclosporine, erythromycin, midazolam, alprazolam, and triazolam. Extracts from fresh and aged garlic inhibited CYP 3A4 in human liver microsomes. The in vivo effects of garlic constituents are found to be species depended and the dosing regimen of garlic constituents appeared to influence the modulation of various CYP isoforms. Studies have indicated that the inhibition of various CYPs by organosulfur compounds from garlic was related to their structure also. Studies using in vitro, in vivo, animal and human models have indicated that various garlic constituents can be the substrates, inhibitors and or inducers of various CYP enzymes. The modulation of CYP enzyme activity and expression are dependent on the type and chemical structure of garlic constituents, dose regime, animal species and tissue, and source of garlic thus this review throws light on the possible herb drug interaction with the use of garlic.