• Title/Summary/Keyword: Therapeutic efficacy

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The Antihyperplastic Effect of Oral Curcuma longa Ingestion in a Rat Model of Benign Prostatic Hyperplasia (강황(薑黃)이 고환절제술 및 testosterone으로 유발된 rat의 전립선비대증에 미치는 영향)

  • Lee, Sang-Hun;Ahn, Young-Min;Ahn, Se-Young;Kim, Young-Ock;Lee, Byung-Cheol
    • The Journal of Internal Korean Medicine
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    • v.30 no.2
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    • pp.355-364
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    • 2009
  • Objectives : Benign prostatic hyperplasia (BPH) is one of the most common diseases among elderly men. Though medicines such as 5${\alpha}$-reductase inhibitor (finasteride) have recently been developed for treating BPH, their adverse effects and low efficacy should not be overlooked. Curcuma longa has a long history of use in traditional medicines of Asian countries. Many reports conclude the component curcumin in Curcuma lonfa, has the potential to treat various diseases including prostate cancer. In this study, we investigated the therapeutic effects and action mechanism of Curcuma longa with a BPH rat model. Methods : Sprague-Dawley rats were used with subcutaneous injection of testosterone after castration, which were histologically similar to human BPH. A total of 30 rats were equally divided into five groups: Group 1 served as control (sham-operated group): Group 2 was the model group: Group 3 and Group 4 animals were administered Curcuma longa at dose levels of 0.5g/kg and 1.0g/kg: Group 5 served as a positive control group and was treated with finasteride at a dose of 1 mg/kg. The drugs were administered orally once a day for 30 days consecutively. After 31 days, the prostates were removed, and analyzed for their prostatic weight and histological examination. Results : The oral Curcuma longa ingestion group showed statistically significant decreases in their prostatic weights compared with the BPH-induced group and the oral finasteride ingestion group (p<0.05). Curcuma longa is also very safe in liver and kidney up to a dose of lg/kg. Injected testosterone histologically led to prostatic hyperplasia in rats, but oral Curcuma longa ingestion decreased this change. Conclusions : These results suggest that Curcuma longa has a definite inhibitory effect on BPH and might be an alternative medicine for treatment and prevention of human BPH.

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A New Histone Deacetylase Inhibitor, MHY4381, Induces Apoptosis via Generation of Reactive Oxygen Species in Human Prostate Cancer Cells

  • Richa, Sachan;Dey, Prasanta;Park, Chaeun;Yang, Jungho;Son, Ji Yeon;Park, Jae Hyeon;Lee, Su Hyun;Ahn, Mee-Young;Kim, In Su;Moon, Hyung Ryong;Kim, Hyung Sik
    • Biomolecules & Therapeutics
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    • v.28 no.2
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    • pp.184-194
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    • 2020
  • Histone deacetylase (HDAC) inhibitors represent a novel class of anticancer agents, which can be used to inhibit cell proliferation and induce apoptosis in several types of cancer cells. In this study, we investigated the anticancer activity of MHY4381, a newly synthesized HDAC inhibitor, against human prostate cancer cell lines and compared its efficacy with that of suberoylanilide hydroxamic acid (SAHA), a well-known HDAC inhibitor. We assessed cell viability, apoptosis, cell cycle regulation, and other biological effects in the prostate cancer cells. We also evaluated a possible mechanism of MHY4381 on the apoptotic cell death pathway. The IC50 value of MHY4381 was lower in DU145 cells (IC50=0.31 µM) than in LNCaP (IC50=0.85 µM) and PC-3 cells (IC50=5.23 µM). In addition, the IC50 values of MHY4381 measured in this assay were significantly lower than those of SAHA against prostate cancer cell lines. MHY4381 increased the levels of acetylated histones H3 and H4 and reduced the expression of HDAC proteins in the prostate cancer cell lines. MHY4381 increased G2/M phase arrest in DU145 cells, and G1 arrest in LNCaP cells. It also activated reactive oxygen species (ROS) generation, which induced apoptosis in the DU145 and LNCaP cells by increasing the ratio of Bax/Bcl-2 and releasing cytochrome c into the cytoplasm. Our results indicated that MHY4381 preferentially results in antitumor effects in DU145 and LNCaP cells via mitochondria-mediated apoptosis and ROS-facilitated cell death pathway, and therefore can be used as a promising prostate cancer therapeutic.

Evaluation of Therapeutic Effect of the Extract from Rhubarb (Rheum officinalis) in Dogs with Chronic Renal Failure (개의 만성 신부전에서 대황 추출물의 치료학적 효과의 평가)

  • Kim, Ye-Won;Hyun, Changbaig
    • Journal of Veterinary Clinics
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    • v.29 no.6
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    • pp.435-440
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    • 2012
  • This study was designed to evaluate the clinical efficacy and safety of Rhubarb extracts ($Rubenal^{(R)}$) in dogs with chronic renal failure (CRF). Client-owned 40 dogs with CRF graded International renal interest Society (IRIS) II-III were enrolled in this study. The dogs were equally allocated and blindly administered with $Rubenal^{(R)}$ or placebo. The following items were evaluated at day 0, 30, 90 and 180: body condition score (BCS), clinical score (appetite, polydipsia/polyuria, quality of life score), hemogram (WBC, RBC, PCV), serum biochemistry (ALT/AST, ALP, Creatinine/BUN, total protein, albumin), serum electrolyte (Na, K, Cl, Ca, P), systolic blood pressure, urinalysis (UPC, USG) and IRIS stage. In this study, we found that the $Rubenal^{(R)}$ preparation was well tolerated by dogs and induced no adverse effects. Statistically significant improvements were observed in clinical score (quality of life score by vet and clients), serum BUN and creatinine levels, serum phosphorus concentration, level of proteinuria, and the IRIS score of CRF in dogs after 6 month of treatment of $Rubenal^{(R)}$. Those findings suggested that the Rhubarb extracts can improve the clinical signs of CRF (i.e. azotemia, hypertension, proteinuria, hyperphosphoremia) and the quality of life (i.e. BCS, clinical score) and can retard the progression of CRF in dogs. Therefore the Rhubarb extracts can be a good supplementary drug for treating dogs with subclinical and clinical renal diseases. However, care should be taken for interpreting our result, because this study is not double-blinded controlled study but pilot study.

Therapeutic evaluation of sustained-releasing praziquantel (SRP) for clonorchiasis: Phase 1 and 2 clinical studies

  • Choi, Min-Ho;Chang, Byung-Chan;Lee, Seung-Jin;Jang, In-Jin;Shin, Sang-Goo;Kho, Weon-Gyu;Chun, Jin-Ho;Hong, Sung-Tae
    • Parasites, Hosts and Diseases
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    • v.44 no.4 s.140
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    • pp.361-366
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    • 2006
  • Sustained-releasing praziquantel (SRP) tablet was designed for single dose treatment regimen of clonorchiasis. A previous pre-clinical study confirmed its sustained-releasing characteristics and a better cure rate than conventional praziquantel (PZQ). In this clinical study, the pharmacokinetics of this SRP tablet were investigated in human volunteers (phase 1; 12 volunteers), and its curative efficacy was examined in clonorchiasis patients (phase 2; 20 volunteers). In the phase 1 clinical study, blood concentrations of both tablets showed wide individual variation. The $AUC_{last}$ of SRP was $497.9{\pm}519.0ng{\cdot}hr/ml\;(mean{\pm}SD)$ and PZQ of $628.6{\pm}695.5\;ng{\cdot}hr/ml$, and the $AUC_{inf}$ of SRP was $776.0{\pm}538.5\;ng{\cdot}hr/ml$ and of PZQ $658.6{\pm}709.9\;ng{\cdot}hr/ml$. $C_{max}$ values of SRP and PZQ were $90.7{\pm}82.2ng/ml\;and\;214.9{\pm}251.9\;ng/ml$, and $T_{max}$ values were $3.42{\pm}1.43\;hr\;and\;1.96{\pm}1.23\;hr$, respectively. SRP tablets showed similar AUC values, but lower $C_{max}$ and longer $T_{max}$ values than PZQ. In the phase 2 study, SRP at 30 mg/kg (single dose) achieved a 60% cure rate and a 95.5% egg reduction rate. The cure rate of a single dose SRP was unsatisfactory compared with that of the conventional PZQ dose, but much better than that achieved by a single dose PZQ.

Enhanced Efficacy of Human Brain-Derived Neural Stem Cells by Transplantation of Cell Aggregates in a Rat Model of Parkinson's Disease

  • Shin, Eun Sil;Hwang, Onyou;Hwang, Yu-Shik;Suh, Jun-Kyo Francis;Chun, Young Il;Jeon, Sang Ryong
    • Journal of Korean Neurosurgical Society
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    • v.56 no.5
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    • pp.383-389
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    • 2014
  • Objective : Neural tissue transplantation has been a promising strategy for the treatment of Parkinson's disease (PD). However, transplantation has the disadvantages of low-cell survival and/or development of dyskinesia. Transplantation of cell aggregates has the potential to overcome these problems, because the cells can extend their axons into the host brain and establish synaptic connections with host neurons. In this present study, aggregates of human brain-derived neural stem cells (HB-NSC) were transplanted into a PD animal model and compared to previous report on transplantation of single-cell suspensions. Methods : Rats received an injection of 6-OHDA into the right medial forebrain bundle to generate the PD model and followed by injections of PBS only, or HB-NSC aggregates in PBS into the ipsilateral striatum. Behavioral tests, multitracer (2-deoxy-2-[$^{18}F$]-fluoro-D-glucose ([$^{18}F$]-FDG) and [$^{18}F$]-N-(3-fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane ([$^{18}F$]-FP-CIT) microPET scans, as well as immunohistochemical (IHC) and immunofluorescent (IF) staining were conducted to evaluate the results. Results : The stepping test showed significant improvement of contralateral forelimb control in the HB-NSC group from 6-10 weeks compared to the control group (p<0.05). [$^{18}F$]-FP-CIT microPET at 10 weeks posttransplantation demonstrated a significant increase in uptake in the HB-NSC group compared to pretransplantation (p<0.05). In IHC and IF staining, tyrosine hydroxylase and human ${\beta}2$ microglobulin (a human cell marker) positive cells were visualized at the transplant site. Conclusion : These results suggest that the HB-NSC aggregates can survive in the striatum and exert therapeutic effects in a PD model by secreting dopamine.

Recent Studies on the Edible Plant Vaccine for Prophylactic Medicine against Microorganism-Mediated Diseases (세균성 질병 예방을 위한 식물 경구 백신 연구 동향)

  • Hahn Bum-Soo;Jeong Young-Jae;Roh Kyung-Hee;Park Jong-Sug;Cho Kang-Jin;Kim Yong-Hwan;Kim Jong-Bum
    • Journal of Plant Biotechnology
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    • v.32 no.4
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    • pp.233-241
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    • 2005
  • Plants have considerable advantages for the production of antigenic proteins because they provide an inexpensive source of protein and an easy administration of vaccine. Since a publication describing edible plant vaccine of HBsAg in 1992, a number of laboratories around the world have studied the use of plants as the bioreactor to produce antigenic proteins of human or animal pathogens. Over the last ten years, these works have been mainly focused on three major strategies for the production of antigenic proteins in plants: stable genetic transformation of either the nuclear or plastid genome, or transient expression in plants using viral vectors. As many antigenic proteins have been expressed in tobacco, also several laboratories have succeeded to express genes encoding antigenic proteins in other crop plants: potato, tomato, maize, carrot, soybean and spinach. At present many works for the production of edible plant vaccine against bacteria-mediated diseases have mostly performed the studies of enterotoxins and adhesion proteins. Also the development of new-type antigens (pili, flagella, surface protein, other enterotoxin and exotoxin etc.) is required for various targets and more efficacy to immunize against microorganism pathogens. Many works mostly studied in experimental animals had good results, and phase I clinical trial of LTB clearly indicated its immunogenic ability. On the other hand, edible plant vaccines have still problems remained to be solved. In addition to the accumulation of sufficient antigen in plants, human health, environment and agriculture regulation should be proven. Also oral tolerance, the physiological response to food antigens and commensal flora is the induction of a state of specific immunological unresponsiveness, needs to be addressed before plant-derived vaccine becomes a therapeutic option.

Compound K improves skin barrier function by increasing SPINK5 expression

  • Park, No-June;Bong, Sim-Kyu;Lee, Sullim;Jung, Yujung;Jegal, Hyun;Kim, Jinchul;Kim, Si-Kwan;Kim, Yong Kee;Kim, Su-Nam
    • Journal of Ginseng Research
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    • v.44 no.6
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    • pp.799-807
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    • 2020
  • Background: The skin acts as a barrier to protect organisms against harmful exogenous agents. Compound K (CK) is an active metabolite of ginsenoside Rb1, Rb2 and Rc, and researchers have focused on its skin protective efficacy. In this study, we hypothesized that increased expression of the serine protease inhibitor Kazal type-5 (SPINK5) may improve skin barrier function. Methods: We screened several ginsenosides to increase SPINK5 gene promoter activity using a transactivation assay and found that CK can increase SPINK5 expression. To investigate the protective effect of CK on the skin barrier, RT-PCR and Western blotting were performed to investigate the expression levels of SPINK5, kallikrein 5 (KLK5), KLK7 and PAR2 in UVB-irradiated HaCaT cells. Measurement of transepidermal water loss (TEWL) and histological changes associated with the skin barrier were performed in a UVB-irradiated mouse model and a 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis-like model. Results: CK treatment increased the expression of SPINK5 and decreased the expression of its downstream genes, such as KLKs and PAR2. In the UVB-irradiated mouse model and the DNCB-induced atopic dermatitis model, CK restored increased TEWL and decreased hydration and epidermal hyperplasia. In addition, CK normalized the reduced SPINK5 expression caused by UVB or DNCB, thereby restoring the expression of the proteins involved in desquamation to a level similar to normal. Conclusions: Our data showed that CK contributes to improving skin-barrier function in UVB-irradiated and DNCB-induced atopic dermatitis-like models through SPINK5. These results suggest that therapeutic attempts with CK might be useful in treating barrier-disrupted diseases.

The Influence of How the Trauma Care System Is Applied at the Trauma Center: The Initial Experience at Single Trauma Center (외상 센터에서의 외상 진료 시스템 도입에 따른 변화: 단일 외상 센터에서의 초기 경험)

  • Kim, Hyung Won;Hong, Tae Hwa;Lee, Seung Hwan;Jung, Myung Jae;Lee, Jae Gil
    • Journal of Trauma and Injury
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    • v.28 no.4
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    • pp.241-247
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    • 2015
  • Purpose: To evaluate the influence of how the trauma care system is applied on the management of trauma patients. Methods: We divided the patients into a pre-trauma system group and a post-trauma system group according to the time when we began to apply the trauma care system in our institution. We compared the general characteristics, injury severity score, initial response time to the trauma patients, number of preventable deaths, and clinical outcomes between the two groups. Results: The numbers of patients in the pre-trauma system group and the post-trauma system group were 188 and 257, respectively. No differences in the patient's median ages, trauma scores (ISS, RTS, TRISS) and proportions of severe trauma patients (ISS>15) were observed between the two groups. The number and the proportion of patients who were admitted to our hospital were increased in the post-trauma system group. The time interval from trauma CP activation to emergency surgery or angio-embolization, and the patient's time spent in emergency room were shortened in the post-trauma system group. However, the lengths of the ICU stay and the hospital stay, and the number of in-hospital mortalities were not improved in the post-trauma system group. In severe trauma patients (ISS>15), there were no differences between the two groups in the number and the proportion of admitted patients, and the time interval from trauma CP activation to performing a diagnostic and therapeutic procedure was not shortened in the post-trauma system group. Conclusion: Application of the trauma care system has shortened the time between the initial response and patient management. However, this improvement was not enough to result in better clinical outcomes. More trauma physicians, multidisciplinary cooperation, and a well-organized trauma management process will be needed if the maximum efficacy of the trauma system is to be achieved.

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Factors Affecting Mental Health and Behavioral Problems in High School Students: Based on a Social Cognitive Career Theory (고등학생의 정신건강 및 문제행동에 영향을 미치는 요인: 사회인지진로이론에 근거하여)

  • Son, Hae Kyoung;Lee, Hyejung;Kim, Miyoung
    • Child Health Nursing Research
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    • v.20 no.4
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    • pp.314-321
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    • 2014
  • Purpose: This study was conducted to identify factors affecting mental health and behavioral problems among high school students through the lens of a Social Cognitive Career Theory. Methods: A descriptive study was carried out with 384 high school students in Seoul, Korea. A self-administrative questionnaire was used. It consisted of items on person background variables, career-related variables including career barriers, learning experiences, self-efficacy, outcome expectations, and career indecision, and mental health and behavioral problems. Descriptive statistics, correlation analysis and multiple regression analysis were performed using the SPSS 21.0 program. Results: The results showed that perceived stress (t=5.12, p<.001), perceived health status (t=-4.08, p=.002), and school record (t=5.46, p<.001) were statistically significant variables. Also, career barriers (t=10.57, p<.001) was a significant factor influencing mental health and behavioral problems. Conclusion: These findings indicate that among career-related variables, career barrier needs to be considered for preventive and therapeutic approach to mental health and behavioral problems in adolescents. Furthermore, the results suggest that career-related stress level should be assessed in high school students on a regular basis.

The Effects of Pulsatilla Koreana for Anti - Inflammatory and Cellular Activity of Periodontal Tissue (백두옹 추출물의 치주조직 세포에 활성도 및 항염 효과에 관한 연구)

  • Jung, Jin-Gwang;Chung, Chin-Hyung;Lim, Sung-Bin;Kim, Jung-Keun;So, Eun-Hee
    • Journal of Periodontal and Implant Science
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    • v.31 no.1
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    • pp.149-165
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    • 2001
  • This study was performed to define the cytotoxicity and the anti-inflammatory action of Pulsatilla koreana extracts. To analyze cytotoxic effects, gingival and periodontal ligament fibroblasts were used, and anti-inflammatory actions related to reduction of $IL-1{\beta}$ and $PGE_2$ production were performed in vitro, for the suggestion of efficacy and safety on periodontal therapeutic use of Pulsatilla koreana extracts. We extracted ethylacetate and butylalcohol from well-dried and ground Pulsatilla koreana throughout multiple processing, then used different concentration solution(0.1 %, 0.2 %, 0.4 %, 0.01 %, 0.02 %, 0.04 %, 1 %, 2 %) of ethylacetate and butylalcohol extracts to examine eytotoxic effects and anti-inflammatory actions Cytotoxic effects were examined by ELISA reader using MTT(Methyl Thiazol-2-YL-2, 5-diphenyl Tetrazolium bromide)solution following culture of human gingival and periodontal ligament fibroblasts. Synthesis of $IL-1{\beta}$was examined by $IL-1{\beta}$ enzyme-immunoassay(EIA)system after separation and culture of monocyte, and $PGE_2$ was examined by $PGE_2EIA$ system after culture of gingival fibroblasts. The results were as follows: 1. In the MTT test of gingival fibroblasts, the change of optical density was decreased significantly at 2 % of butylalcohol extracts and 0.04 %, 0.1 %, 0.2 %, 0.4 %, 1 %, 2 % of ethylacetate extracts.(p<0.05) 2. In the MTT test of periodontal ligament cells, the change of optical density were not differ significantly. but butylalcohol and ethylacetate extracts except from butylalcohol 0.01 % showed high cell cytotoxity. 3. Both ethylacetate and butylalcohol extracts from Pulsatilla koreana inhibited the synthesis of $IL-1{\beta}$and inhibition effect of ethylacetate extracts were higher than butylalcohol extracts. 4. Both ethylacetate and butylalcohol extracts from Pulsatilla koreana inhibited the synthesis of $PGE_2$, and ethylacetate extracts were higher than butylalcohol extracts. In conclusion, ethylacetate and butylalcohol extracts from Pulsatilla koreana showed little cell cytotoxity for gingival and periodontal ligament fibroblasts, and the inhibition of $IL-1{\beta}$ and $PGE_2$ sysnthesis, therefore it is considered that these extracts can be developed as the therapeutics of the periodontal disease.

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