• Title/Summary/Keyword: Therapeutic range

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Inhibitory effect of the aqueous extract of a tetraploid 'etteum' variety in Platycodon grandiflorum on degranulation and inflammatory mediator release in RBL-2H3 cells (으뜸도라지추출물이 RBL-2H3 세포에서 탈과립과 염증매개물질의 분비 억제에 미치는 영향)

  • Jung, Jae In;Kim, Hyung Seo;Ji, Han Kyeol;Lee, Hyun Sook;Lee, Jae-Yong;Kim, Eun Ji
    • Journal of Nutrition and Health
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    • v.51 no.3
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    • pp.208-214
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    • 2018
  • Purpose: Platycodon grandiflorum (a domestic diploid variety, DV-PG) has been used as a food and component of various traditional oriental medicines. Although DV-PG is known to have an anti-allergic effect, little is known about the beneficial health effects of the tetraploid 'Etteum' variety in the Platycodon grandiflorum (TV-PG), which is a recently developed variety. In this study, we investigated the effect of TV-PG on the rat basophilic leukemia mast cell (RBL-2H3)-mediated allergic response. Methods: To examine the effects of TV-PG on the allergic response, RBL-2H3 cells were sensitized with dinitropheny (DNP)-immunoglobin E, treated with various concentrations of TV-PG, and challenged with DNP-human serum albumin. We estimated cell granulation by measuring the release of ${\beta}$-hexosaminidase and production of inflammatory mediators by ELISA. Results: TV-PG had no effect on the proliferation or cytotoxicity of RBL-2H3 cells within the concentration range of 0 to $200{\mu}g/mL$. TV-PG inhibited degranulation of RBL-2H3 cells by antigen stimulation in a dose-dependent manner. TV-PG also suppressed the production of inflammatory cytokines and mediators such as interleukin-4, tumor necrosis $factor-{\alpha}$, prostagladin E2, and leukotriene B4 in RBL-2H3 cells by antigen stimulation. Conclusion: These results indicate that TV-PG exhibits anti-allergic activity via inhibition of degranulation as well as suppression of inflammatory mediators and cytokine release. These findings suggest that TV-PG may have potential as a preventive and therapeutic agent for the treatment of various allergic diseases.

Clinical Outcome of Turkish Metastatic Breast Cancer Patients with Currently Available Treatment Modalities - Single Center Experience

  • Cabuk, Devrim;Basaran, Gul;Teomete, Mehmet;Dane, Faysal;Korkmaz, Taner;Seber, Selcuk;Telli, Ferhat;Yumuk, Perran Fulden;Turhal, Serdar
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.117-122
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    • 2014
  • Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related death among women in the developed countries. Despite advances in screening, improved local therapies and adjuvant systemic treatments, median survival of metastatic breast cancer patients (MBC) is in the range of 2-3 years at most. We aimed to investigate whether the prognostic factors and therapeutic responses of our Turkish patients are similar to those in the literature. Materials and Methods: We reviewed the medical records of MBC patients who had been treated in our institution between 1999-2009 and analyzed their clinicopathological features and survival outcomes retrospectively Results: A hundred and sixty patients were included. Median age was 47 (23-82), median follow up was 24 (2-186) months. At the time of diagnosis 59% of patients were under the age of 50 and 46% were postmenopausal. The majority (37%) had multiple sites of metastases. Forty percent received endocrine therapy and 40% chemotherapy as first line metastatic treatment. Thirty (20%) patients were treated with molecular targeting agents like trastuzumab, lapatinib and sunitinib, frequently combined with a chemotherapy agent. Five-year overall survival (OS) was 32% and median OS was 38 months for the whole group. Five year progression free survival (PFS) was 10% and median PFS was 10 months. Menopausal status, hormone receptor expression and disease free status had a significant impact on overall survival in the multivariate analysis (p 0.018, p 0.018 and p:0.003, respectively). Conclusions: All our patients were treated with the modern oncologic therapies recommended by the international guidelines. From our data, MBC patients live up to 3-4 years, indicating that further improvement beyond that requires development of new treatment modalities. The survival outcomes of our patients were consistent with the data reported in the literature.

RNAi and miRNA in Viral Infections and Cancers

  • Mollaie, Hamid Reza;Monavari, Seyed Hamid Reza;Arabzadeh, Seyed Ali Mohammad;Shamsi-Shahrabadi, Mahmoud;Fazlalipour, Mehdi;Afshar, Reza Malekpour
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7045-7056
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    • 2013
  • Since the first report of RNA interference (RNAi) less than a decade ago, this type of molecular intervention has been introduced to repress gene expression in vitro and also for in vivo studies in mammals. Understanding the mechanisms of action of synthetic small interfering RNAs (siRNAs) underlies use as therapeutic agents in the areas of cancer and viral infection. Recent studies have also promoted different theories about cell-specific targeting of siRNAs. Design and delivery strategies for successful treatment of human diseases are becomingmore established and relationships between miRNA and RNAi pathways have been revealed as virus-host cell interactions. Although both are well conserved in plants, invertebrates and mammals, there is also variabilityand a more complete understanding of differences will be needed for optimal application. RNA interference (RNAi) is rapid, cheap and selective in complex biological systems and has created new insight sin fields of cancer research, genetic disorders, virology and drug design. Our knowledge about the role of miRNAs and siRNAs pathways in virus-host cell interactions in virus infected cells is incomplete. There are different viral diseases but few antiviral drugs are available. For example, acyclovir for herpes viruses, alpha-interferon for hepatitis C and B viruses and anti-retroviral for HIV are accessible. Also cancer is obviously an important target for siRNA-based therapies, but the main problem in cancer therapy is targeting metastatic cells which spread from the original tumor. There are also other possible reservations and problems that might delay or even hinder siRNA-based therapies for the treatment of certain conditions; however, this remains the most promising approach for a wide range of diseases. Clearly, more studies must be done to allow efficient delivery and better understanding of unwanted side effects of siRNA-based therapies. In this review miRNA and RNAi biology, experimental design, anti-viral and anti-cancer effects are discussed.

Occurrence and characterization of oseltamivir-resistant influenza virus in children between 2007-2008 and 2008-2009 seasons

  • Kim, Seoung Geun;Hwang, Yoon Ha;Shin, Yung Hae;Kim, Sung Won;Jung, Woo Sik;Kim, Sung Mi;Oh, Jae Min;Lee, Na Young;Kim, Mun Ju;Cho, Kyung Soon;Park, Yeon Gyeong;Min, Sang Kee;Lee, Chang Kyu;Kim, Jun Sub;Kang, Chun;Lee, Joo Yeon;Huh, Man Kyu;Kim, Chang Hoon
    • Clinical and Experimental Pediatrics
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    • v.56 no.4
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    • pp.165-175
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    • 2013
  • Purpose: There was a global increase in the prevalence of oseltamivir-resistant influenza viruses during the 2007-2008 influenza season. This study was conducted to investigate the occurrence and characteristics of oseltamivir-resistant influenza viruses during the 2007-2008 and 2008-2009 influenza seasons among patients who were treated with oseltamivir (group A) and those that did not receive oseltamivir (group B). Methods: A prospective study was conducted on 321 pediatric patients who were hospitalized because of influenza during the 2007-2008 and 2008-2009 influenza seasons. Drug resistance tests were conducted on influenza viruses isolated from 91 patients. Results: There was no significant difference between the clinical characteristics of groups A and B during both seasons. Influenza A/H1N1, isolated from both groups A and B during the 2007-2008 and 2008-2009 periods, was not resistant to zanamivir. However, phenotypic analysis of the virus revealed a high oseltamivir $IC_{50}$ range and that H275Y substitution of the neuraminidase (NA) gene and partial variation of the hemagglutinin (HA) gene did not affect its antigenicity to the HA vaccine even though group A had a shorter hospitalization duration and fewer lower respiratory tract complications than group B. In addition, there was no significant difference in the clinical manifestations between oseltamivir-susceptible and oseltamivir-resistant strains of influenza A/H1N1. Conclusion: Establishment of guidelines to efficiently treat influenza with oseltamivir, a commonly used drug for treating influenza in Korean pediatric patients, and a treatment strategy with a new therapeutic agent is required.

Human Neutrophil Cathepsin G: In Vivo Synthesis of Anti-HNCG Antibody, Inhibition of the Activity of HNCGs and Mechanism of the Inhibitions (사람 호중구 Cathepsin G: Anti-HNCG Ab의 In Vivo 합성, HNCG의 활성도 억제와 그 기전에 관한 연구)

  • Bae, Sung-Jun;Kim, Woo-Mi;Kim, Ki-Chan;Chang, Myung-Woong;Kang, Koo-Il
    • The Korean Journal of Pharmacology
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    • v.27 no.2
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    • pp.145-153
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    • 1991
  • Human neutrophil cathepsin-G, which has been known as one of the active enzymes causing inflammatory diseases, was purified by two steps procedure involving one size exclusion (Ultorogel AcA54) and one ion exchange (CM-Sephadex) chromatography. Purified HNCGs were cross-reacted with Anti-HNCathepsin-G antibodies which were radised in rabbits and purified by cathepsin-G labeled Sepharose 4B affinity chromatography. HNCGs were effectively inhibited by NSAIDs including phenylbutazone, sulindac, oxyphenbutazone, salicylic acid and salicyluric acid. $IC_{50}_s$ of these drugs for inhibition of Cathepsin G were 0.3-0.8 mM. Other NSAIDs including aspirin showed little or no inhibition effect on the activity of Cathepsin G. These results strongly indicated that NSAIDs which showed inhibition effect on the activity of HNCGs possibly be at least a part of mechanism of action which might be related to direct inhibition of cathepsin G at the tissue destruction sites beside of their known mechanism of action as an anticyclo-oxygenase in treatment of inflammatory diseases. Lipid soluble component of Korean Red Ginseng which was known as an anti-inflammatory agent inhibited HNCGs strongly, but no other fractions did inhibited HNCGs. Antibiotics including novobiosin and rifamycin showed some inhibition effect on HNCGs, i. e.., $IC_{50}$ of these drugs were 2.6 mM and 1.5 mM respectively, and other antibiotics including penicillin G showed no or negligible inhibition effect on the activity of HNCGs. However. tetracyclines inhibited HNCGs very effectively at the concentration of therapeutic range. The inhibition effect of the activity of HNCGs by tetracycline are not related to the N-dimethyl radical on the 4 position of the tetracycline molecule. Furthermore, N-dedimethylated tetracyclines may have beneficial effect for long term treatment of chronic inflammatory diseases without developing any drug resistance to microorganisms.

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The Effect of Additional Mobilization with Conservative Physical Therapy in Patients with Frozen Shoulder on ROM and Subjective Pain Scale (동결 견 환자에 대한 보존적 물리치료와 관절 가동술의 병행이 주관적 통증지수와 관절가동범위에 미치는 효과)

  • Hyong, In-Hyouk;Ha, Mi-Sook
    • The Journal of the Korea Contents Association
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    • v.9 no.11
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    • pp.271-279
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    • 2009
  • Frozen shoulder is clinically characterized by pain and reduced ROM. The therapeutic goal of frozen shoulder can be reducing pain and increasing ROM in shoulder joint, resulting in improvement of joint movement. Therefore, this study was conducted to know the effect of mobilization in parallel with conservative physical therapy(H/P, TENS, U/S) in patients with frozen shoulder on subjective pain scale and ROM. 26 patients diagnosed with frozen shoulder were included for study. Among them, 13 patients(experiment group) were managed by mobilization as well as conservative physical therapy, another 13 patients(control group) were only treated by conservative physical therapy alone. All the patients were treated three times a week for 4 weeks, and after each treatment subjective pain scale and ROM were measured. In experimental group, pain has decreased and ROM has increased in abduction, external rotation and internal rotation. In control group, pain has also decreased but ROM has not changed in abduction, external rotation and internal rotation. There were no significant difference in subjective pain scale between two groups but some difference in ROM (external rotation, internal rotation). According to the results, we concluded that both conservative physical therapy and joint mobilization technique are more effective for increasing ROM especially external rotation, internal rotation than conservative physical therapy alone.

LB30057, an Orally Effective Direct Thrombin Inhibitor, Prevents Arterial and Venous Thrombosis in Rats and Dogs

  • Park, Hee-Dong;Kim, Hee-Jin;Oh, Yeong-Soo;Kim, In-Chull;Kim, Yong-Zu;Koh, Hyun-Chul;Shin, In-Chul;Lee, Yong-Hee;Lee, Chang-Ho
    • Archives of Pharmacal Research
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    • v.26 no.3
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    • pp.224-231
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    • 2003
  • The anti-thrombotic effects of LB30057, a direct thrombin inhibitor, were evaluated with in vivo rat and dog thrombosis models. In rats, 1 mg/kg of LB30057 inhibited half of the clot formations in the inferior vena cava at 5 minutes after intravenous application. When measured at 2 hours after oral application, 100 mg/kg prevented approximately half of the clot formations in the inferior vena cava and 50 mg/kg prolonged the mean occlusion time from $15.6{\pm}1.3$ minutes to $47.2{\pm}8.3$ minutes in the carotid artery. In dogs, the formation of thrombus in the jugular vein was reduced to half at a dose range of 20-30 mg/kg at 6 hours after oral application. In addition, the LB30057 dosage required to reduce venous clot formation by approximately 80-90% in dogs was only about 10% of that required for the same reduction in rats. This is probably due to the variation in its time-dependent blood concentration profiles in each species; for example, the plasma half-life of LB71350 in dogs was longer than that in rats ($153.0{\pm}3.0$ vs. $129.7{\pm}12.7$ min at 30 mg/kg, i.v., respectively). AUG, $T_{max},{\;}G_{max}$, and BA in dogs were 59, 8.9, 9.17, and 13.3 times higher than those in rats at oral 30 mg/kg, respectively. Taken together, these results suggest that LB30057 administered orally is effective in the prevention of arterial and venous thrombosis in rats and dogs. It therefore represents a good lead compound for investigations to discover a new, orally available, therapeutic agent for treating thrombotic diseases.

Evaluation of Prescription Data for Development of Warfarin Nomogram in Korean Patients with Cerebral Infarction (뇌졸중 환자군의 Warfarin Nomogram 설정을 위한 실제 처방전 평가)

  • Jang, Ju-Young;Ko, Kyung-Mi;Yoon, Ji-Yeon;Han, Ok-Yeon;Lim, Sung-Cil
    • YAKHAK HOEJI
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    • v.53 no.2
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    • pp.83-88
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    • 2009
  • Warfarin is the most widely used oral anticoagulant in the world but maintenance of proper therapeutic range and prevention of adverse drug events always need to be careful. Especially, in Korea, warfarin dosing for patients with cerebral infarction is currently based on the nomogram which is done by foreign clinical trials not for the Korean. Therefore we evaluate warfarin dose of patients in the neurology and eventually get the base data of warfarin nomogram for Korean with stroke. We performed this study retrospectively on reviewing the medical charts to evaluate the prescribed loading dose (LD) and maintenance dose (MD) of warfarin and each responding International Normalized Ratio (INR) with any bleeding adverse drug reaction including of patient's characteristics for total 75 patients with stroke in the department of neurology of Kangnam ST. Mary's Hospital from January 2005 to June 2008. All evaluated patients should not be treated with warfarin in the past at all and should be initiated warfarin therapy first.ly at this time. All evaluated patients were divided as two classes by wafarin LD which is; 1) HDG - a high loading dosing group prescribed over 5mg, and 2) LDG - a low loading dosing group prescribed 5mg or below. As a result, average LD was $9.34{\pm}0.22$ mg (p=0.000) in HDG and $4.25{\pm}0.39$ mg (p=0.000) in LDG. Average baseline INR was $0.91{\pm}0.05$ (p=0.161) in HDG and $1.26{\pm}0.14$ (p=0.002) in LDG. On the first and second week, daily MD was $4.21{\pm}0.14$ mg (p=0.000) and $2.96{\pm}0.19$ mg (p=0.696) in HDG and also in LDG, $2.95{\pm}0.29$ mg (p=0.000) and $3.14{\pm}0.36$ mg (p=0.696). Also average reacting daily INR was respectively $2.53{\pm}0.12$ (p=0.141) and $2.51{\pm}0.16$ (p=0.678) in HDG, and in LDG, $2.11{\pm}0.17$ (p=0.141) and $2.42{\pm}0.14$ (p=0.678). After the second week, INR was not measured in regularly. Also most of underlying diseases were hypertension (n=38), diabetes mellitus (n=14), dyslipidemia (n=8) in order. Four ADRs with simple hemorrhage were occurred and those were due to drug interaction by comedication. In the conclusion, proper starting LD for Korean with stroke is 10 mg if baseline INR is around 1.0 or 5 mg if over 1.3. Proper MD need to be more evaluated in the future for setting up warfarin nomogram to make prospective study.

Antioxidant, Anti-wrinkle and Whitening Effect of Fermented Extracts of Hwangryunhaedoktang (황련해독탕 발효물의 항산화, 항주름 및 미백 효과)

  • Um, Ji Na;Min, Jin Woo;Joo, Kwang Sik;Kang, Hee Cheol
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.43 no.1
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    • pp.69-78
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    • 2017
  • Hwangryunhaedoktang (HHT) has been traditionally used as a preventive and therapeutic medicine to treat enervation and diverse chronic diseases. This study was designed to compare the antioxidant, anti-wrinkle and whitening effects of HHT extract and its fermented extract by Leuconostoc mesenteroides (FHHT). FHHT was prepared by inoculation of L. mesenteroides after the extraction procedure with 70% ethanol. HHT and FHHT was investigated via high-performance liquid chromatography (HPLC). Simultaneous qualitative analysis of two bioacitive components, berberine and palmatine. was achieved by comparing their retention times ($t_R$) and UV spectra with those of the standard components. Cell viability test results indicated that both HHT and FHHT were non-toxic. In DPPH radical scavenging ability, $SC_{50}$ values of the FHHT was $68.85{\mu}g/mL$, which is more effective than HHT. Moreover, FHHT showed higher expression in production of procollagen type I than HHT. In nontoxic concentration range, FHHT showed strong melanin production inhibitory effect in ${\alpha}-melanocyte$ stimulating hormone (${\alpha}-MSH$)-stimulated B16F10 cell ($IC_{50}=9.82{\mu}g/mL$). These results suggested that fermented extracts of hwangryunhaedoktang had considerable potential as a cosmetics ingredient with an antioxidant and anti-wrinkle and whitening effects.

A novel herbal formulation consisting of red ginseng extract and Epimedium koreanum Nakai-attenuated dextran sulfate sodium-induced colitis in mice

  • Saba, Evelyn;Lee, Yuan Yee;Kim, Minki;Hyun, Sun-Hee;Park, Chae-Kyu;Son, Eunjung;Kim, Dong-Seon;Kim, Sung-Dae;Rhee, Man Hee
    • Journal of Ginseng Research
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    • v.44 no.6
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    • pp.833-842
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    • 2020
  • Background: Ulcerative colitis (UC) is a commonly encountered large intestine disease in the contemporary world that terminates into colorectal cancer; therefore, the timely treatment of UC is of major concern. Panax ginseng Meyer is an extensively consumed herbal commodity in South East Asian countries, especially Korea. It exhibits a wide range of biologically beneficial qualities for almost head-to-toe ailments in the body. Epimedium koreanum Nakai (EKN) is also a widely used traditional Korean herbal medicine used for treating infertility, rheumatism, and cardiovascular diseases. Materials and methods: Separately the anti-inflammatory activities of both red ginseng extracts (RGEs) and EKNs had been demonstrated in the past in various inflammatory models; however, we sought to unravel the anti-inflammatory activities of the combination of these two extracts in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice model because the allopathic remedies for UC involve more side effects than benefits. Results: Our results have shown that the combination of RGE + EKN synergistically alleviated the macroscopic lesions in DSS-induced colitic mice such as colon shortening, hematochezia, and weight loss. Moreover, it restored the histopathological lesions in mice and decreased the levels of proinflammatory mediators and cytokines through the repression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP-3) expression. In vitro, this combination also reduced the magnitude of nitric acid (NO), proinflammatory mediators and cytokine through NF-κB and mitogen-activated protein kinase (MAPK) pathways in RAW 264.7 mouse macrophage cells. Conclusion: In the light of these findings, we can endorse this combination extract as a functional food for the prophylactic as well as therapeutic treatment of UC in humans together with allopathic remedies.