• Title/Summary/Keyword: AAG

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Efficacy of Needling at Sympathetic Point (an Auricular Acupuncture Point) in Migraine Patients: A Randomized Controlled Study

  • O. Deepika;A. Mooventhan;N. Mangaiarkarasi;N. Manavalan
    • Journal of Acupuncture Research
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    • v.41 no.2
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    • pp.115-120
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    • 2024
  • Background: Migraine is a common disabling headache that affects every aspect of a person's life. Auricular acupuncture is a cost-effective treatment modality for the management of painful neurological conditions. Previous studies have shown the beneficial effects of a combination of ear points in the management of migraines. However, no studies have evaluated the efficacy of a single auricular point (i.e., sympathetic point) in migraine. Thus, this study evaluated the efficacy of sympathetic points on pain intensity and depression levels in patients with migraine. Methods: In this randomized controlled study, 100 patients with migraine aged 18-45 years were randomly divided into either an auricular acupuncture group (AAG) (n = 50) or a placebo control group (PCG) (n = 50). The AAG underwent needling at the sympathetic point (an auricular acupuncture point), whereas the PCG underwent needling at a non-acupuncture point for 20 minutes daily for 7 days. Assessments were performed before and after the intervention using a 6-item headache impact test (HIT-6) and Beck depression inventory (BDI) scale. Statistical analyses were performed using SPSS version 16. Results: In within-group analysis, the AAG showed a significant reduction in HIT-6 and BDI, whereas the PCG showed a significant increase in HIT-6 and a significant reduction in BDI. In between-groups analyses, HIT-6 reduced significantly in the AAG compared with that in the PCG, whereas BDI reduced significantly in the PCG compared with that in the AAG. Conclusion: In patients with migraine, needling at the sympathetic point produces a greater reduction in the pain intensity level and lesser reduction in the depression level compared to needling at a non-acupuncture point.

Protein Binding of Disopyramide -Displacement by Mono-N-Dealkyl-Disopyramide and Variation with Commerial Source of Alpha-1-Acid Glycoprotein-

  • Haughey, David B.;Steinberg, Irving;Lee, Min-Hwa
    • Journal of Pharmaceutical Investigation
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    • v.15 no.1
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    • pp.1-7
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    • 1985
  • Previous studies show that the free (unbound) fraction of disopyramide in human serum is drug concentration dependent~ at corresponding serum disopyramide concentrations that are achieved clinically. $^1^{\sim}^3^)\;Moreover$, disopyramide free fraction values vary several fold at any given drug concentration in human serum and tend to decrease as serum cocentrations of alpha-I-acid glycoprotein(AAG) incrase.$^4^)$ A recent $study^5^)$ demonstrates that the free fraction of disopyramide inhuman serum increases almost 2-fold following the addition of $14.4{\mu}M/L$ mono-N-dealkyldisopyramide. These studies and others. $^6^),\;^7^)$ prompted the present investigation to characterize the protein binding of disopyramide in human serum and solutions of AAG in the presence of mono-N-dealkyldisopyramide (a major metabolite of, disopyramide) and to determine the utility of using commercially available alpha-I-acid glycoprotein for drug protein binding displacement studies. Because many basic and acidic compounds are known to bind to alpha-I-acid $glycoprotein^8^)$ the present study. was performed to determine whteher commercially available AAG would provide a convenient protein source for such binding studies.

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Recent Research Trends in American Geomorphology and Hydrogeography (미국에서의 지형학과 수문지리학의 최근 연구동향)

  • Chang Heejun;Kim Changhwan
    • Journal of the Korean Geographical Society
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    • v.39 no.6 s.105
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    • pp.873-887
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    • 2004
  • We examined research trends in geomorphology and hydrogeography in America based on papers presented at the annual meetings of the Association of American Geographers(AAG) and papers published in two AAG journals between 2002 and 2004. Among the 437 papers in geomorphology, $40\%$ of the papers concerned fluvial geomorphology, followed by environmental geomorphology and glacial and periglacial geomorphology concern. Among the 452 papers in hydrogeography, about $20\%$ of the papers focused on water, law and institutional aspects, followed by hydrogeomorphology and hydrologic modeling. Twenty one papers examining geomorphology and hydeogeography were published in two AAG journals, and fluvial geomorpholoy was the dominant theme. GIS was used for $29\%$ papers in geomorphology and $35\%$ of papers in hydrogeography($35\%$), suggesting that other methods, including geostatistics, field survey, and qualitative methods, are employed as well. This methodological diversification seems to be associated with solving such complex environmental problems as integrated watershed management and implies that geomorphologists and hydrogeographers are expanding their traditional territories and are making close connections with human-environment geographers and human geographers. Geomorphologists and hydrogeographers are likely to continue examining the causes of and solving environmental problems that humans are currently facing and might face in the future.

Cancer Chemoprevention Effects of Geldanamycin and 17-AAG in Human Oral Squamous Cell Carcinoma (Geldanamycin과 17-AAG가 구강편평세포암종 세포주에 미치는 암예방 효과)

  • Lee, Eun Ju
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.4
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    • pp.462-469
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    • 2018
  • HSP90 regulates various proteins involved in differentiation and cell survival. Levels of HSP90 tend to increase during development of squamous cell carcinoma in the head and neck including the mouth. Thus, many studies have been conducted to treat these cancers through suppression of HSP90. This study investigated the effect of two HSP90 inhibitors, geldanamycin and 17-AAG, on the proliferation, apoptosis, and invasion of human oral squamous cell carcinoma cells. Cell survival and cell cycle analyses, as well as western blot analysis, were performed with oral cancer cell lines, YD-10B and YD-38. After treatment with HSP90 inhibitors, cell proliferation was significantly inhibited. When YD-10B and YD-38 cells were treated with various concentrations of geldanamycin and 17-AAG (0, 0.1, 0.3, 1 and $10{\mu}M$) for 24 hr, the growth of YD-10B cells was markedly reduced compared to that of YD-38 cells. Thereafter, the cells were subjected to flow cytometry, which revealed G2 arrest. These results demonstrated that geldanamycin induced G2 arrest and inhibited cell proliferation through the $p-GSK-3{\beta}$ pathway in YD-10B and YD-38 cells, thus inhibiting cell survival. HSP90 inhibitors are therefore expected to have a therapeutic effect on various cancer cell lines.

칼슘 길항제의 혈장 단백결합에 미치는 Glycyrrhizic acid의 영향

  • 박혜정;이치호;신영희
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.343-343
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    • 1994
  • 1. 목 적 : 혈액 중에 존재하는 약물은 대부분 혈장 단백질과 결합하며, 비단백 결합성 약물만이 생체막을 통과하여 여러 조직에 분포되고, target eel1에서 약리학적 작용을 나타내며, 대사, 배설 될 수 있다. 단백결합율이 높은 약물일수록 비결합성 약물의 양은 적어지며, 따라서 비결합성 약물의 증가는 약효의 상승을 의미하게 된다. 최근 만성 질환에 한약의 병용투여가 증가하고 있다. 본 실험에서는 단백결합율이 높은 감초의 주성분인 Glycyrrhizic acid(GA)와 고혈압 치료제로 많이 사용되는 칼슘 길항제를 병용 투여할 경우, 칼슘 길항제의 혈장 단백결합에 미치는 영향을 살펴 보았다. 2. 방 법 : Diltiazem hydrochloride, Verapamil hydrochloride, Nifedipine 와 GA를 model 약물로 하여 평형 투석법과 한외 여과법을 이용하여 fatty acid free human serum albumin(HSA), Low density lipoprotein( LDL ), of-Acid glycoprotein(AAG), plasma 각각에 대한 결합율을 HPLC로 분석하였으며 또한 Scatchard plot를 이용하여 binding parameter를 구하였다. 3. 결과 및 고찰 : GA는 Diltiazem의 HSA와 plasma의 결합율에 영향을 미쳤으며, Verapamil의 HSA, LDL, AAG, Plasma 결합율에, 그리고 Nifedipine의 HSA, LDL, Plasma의 단백 결합율에 영향을 주었으며, 각각 n과 Ka값에 변화를 주었다.

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Differential Sensitivities of Human Multidrug-resistant Cancer Cells to BIIB021 and Modulation of Hsp90 Inhibitors by NSAIDs and Niclosamide (항암제 다제내성(MDR) 암세포의 Hsp90 저해제 BIIB021에 대한 감수성의 차이 및 NSAIDs 및 Niclosamide에 의한 Hsp90 저해제의 활성 변화)

  • Moon, Hyun-Jung;Lee, Su-Hoon;Kim, Sun-Hee;Kang, Chi-Dug
    • Journal of Life Science
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    • v.28 no.10
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    • pp.1212-1219
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    • 2018
  • The critical role of heat shock protein 90 (Hsp90) in tumorigenesis led to the development of several first- and second-generation Hsp90 inhibitors, which have demonstrated promising responses in cancers. In this study, we found second-generation Hsp90 inhibitor BIIB021-resistant multidrug-resistant (MDR) human cancer cells, although BIIB021 was shown to be active in first-generation Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-resistant MDR cells. MCF7-MDR and HeyA8- MDR cells were more resistant to BIIB021 than their parental counterparts, indicating that BIIB021 cannot be applicable to all cancer cells expressing MDR proteins. We revealed that dimethyl-celecoxib (DMC), one of the non-steroidal anti-inflammatory drugs (NSAIDs), potentiated cytotoxicity of BIIB021 against both BIIB021-resistant and BIIB021-sensitive MDR cells. The effectiveness of NSAIDs involving celecoxib and DMC in combination with BIIB021 led to the autophagic degradation/down-regulation of mutant p53 (mutp53) that overexpressed MDR cells and the suppression of Hsp70 induction. This resulted in sensitization of MDR cells to BIIB021. Moreover, autophagy induction by sulindac sulfide, another type of NSAID, and niclosamide, an FDA-approved anthelmintic drug, potentiated 17-AAG-mediated autophagic degradation/down-regulation of mutp53 and c-Myc, client proteins of Hsp90. Therefore, our results suggest that NSAIDs and niclosamide positively enhance the anticancer activity of Hsp90 inhibitors through an autophagic pathway. They may also be new candidates for sensitizing MDR cells to Hsp90 inhibitors.

SIRT1 Inhibitor Enhances Hsp90 Inhibitor-mediated Abrogation of Hsp90 Chaperone Function and Potentiates the Cytotoxicity of Hsp90 Inhibitor in Chemo-resistant Human Cancer Cells (SIRT1 inhibitor에 의한 Hsp90 inhibitor의 Hsp90 샤페론 기능 억제 및 항암제 내성세포의 Hsp90 inhibitor에 대한 세포독성 증강)

  • Moon, Hyun-Jung;Lee, Su-Hoon;Kim, Hak-Bong;Lee, Kyoung-A;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
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    • v.26 no.7
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    • pp.826-834
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    • 2016
  • The present investigation was undertaken to examine the effectiveness of the combination treatment of an Hsp90 inhibitor and a SIRT1 inhibitor on suppressing the growth of chemo-resistant human cancer cells. We showed that inhibition of SIRT1 effectively potentiated the cytotoxicity of 17-allylamino-17-demethoxygeldanamycin (17-AAG) and reversed Hsp90 inhibitor resistance in multidrug-resistant (MDR) human ovarian HeyA8-MDR cells. Amurensin G, a potent natural SIRT1 inhibitor, enhanced Hsp90 inhibitor-mediated abrogation of the Hsp90 chaperone function and accelerated degradation of mutated p53 (mut p53), an Hsp90 client protein, by up-regulation of ubiquitin ligase CHIP. Knock-down of CHIP significantly attenuated amurensin G-induced mut p53 degradation. Down-regulation of mut p53 reduced the expression of heat shock factor1 (HSF1)/heat shock proteins (Hsps), a major cause of Hsp90 inhibitor resistance, which led to sensitization of the MDR cells to the Hsp90 inhibitor by the SIRT1 inhibitor. Amurensin G potentiated cytotoxicity of the Hsp90 inhibitor in HeyA8-MDR cells through suppression of 17-AAG-induced Hsp70 and Hsp27 induction via down-regulation of mut p53/HSF1, and it caused activation of PARP and inhibition of Bcl-2. Our data suggests that SIRT1 inhibitors could be used to sensitize MDR cells to Hsp90 inhibitors, possibly through suppression of the mut p53/HSF1-dependent pathway, and a novel mut p53-directed action of SIRT1 inhibition could effectively prevent mut p53 accumulation in MDR cells.

Development of AFLP and STS Markers Related to Stay Green Trait in Multi-Tillered Maize

  • Jang Cheol Seong;Lee Hee Bong;Seo Yong Weon
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.49 no.4
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    • pp.358-362
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    • 2004
  • In order to develop molecular markers related to stay green phenotype, AFLP analysis was conducted using near-isogenic lines for either stay green or non stay green trait. Both lines have characteristics of multi-ear and tillers (MET). Two out of 64 primer combinations of selective amplification identified three reproducible polymorphic fragments in MET corn with stay green. Both of E+AGC/M+CAC and E+AAG/M+CAA primer combinations produced two and one specific polymorphic fragments linked to stay green trait, respectively. For the conversion of AFLPs to sequence tag sites (STSs), primers were designed form both end sequences of each two polymorphic fragments. One fragment, which was amplified with E+AAG/M+CAA primer combinations, possessed 298 bp long and showed a $91\%$ homology with maize retrotransposon Cinful-l. One out of two polymorphic fragments produced with E+AGC/M+CAC primer combination had 236 bp long and matched a $96\%$ homology with an intron region of 22kDa alpha zein gene cluster in Zea mays. One out of two PCR fragments amplified with MET2 primer set in the stay green MET was not produced in the non-stay green MET. The developed AFLP and STS marker could be used as an efficient tool for selection of the stay green trait in the MET inbred.