• Title/Summary/Keyword: Dose loss

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Study on Development of Assessment Guideline and Endpoints for Clinical Trial with Antitumor Natural Products (천연물 항암제제 임상시험 평가지표 개발연구)

  • Namgung, Mi-Ae;Chang, Yoo-Sung;Jeong, Seung-Gi;Kim, Jin-Seung;Yoon, Sung-Woo;Jang, Ki-Young;Yoo, Hwa-Seung;Jung, Myeon-Woo;Lee, Sung-Ho;Kim, Sung-Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1678-1727
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    • 2006
  • This study was perfromed to develop the assessment guideline and endpoints for clinical trial with anticancer herbal medicine. The botanical products used to humans for long time may be applied to phase 3 clinical trial after submitting the evidences for safety and efficacy of them or completion of basic requirement of phase 1 and phase 2 for safety confirmation and dose determination. Syndrome improvement was chiefly evaluated by Zubrod and karnofsky(%) methods. We suggest the general clinical trial assessment with botanical products, by following assessment points, that is, tumor size for 50 points, survival fate for 10 points, major syndromes for 40 points. It is recommendable that the each symptom of Qi deficiency syndrome, blood deficiency syndrome and Qi stagnation syndrome was allocated by assessment points, Similarly, the each symptom was given the assessment points according to the severity of symptom, for example, slight for 3 points, moderate for 2 points and severe for 1 point in hepatocelluar carcinoma and lung cancer. Then, the efficacy of botanical products was evaluated by the difference between pre-treatment and post-treatment. Asking the neoplastic patients of questionnaire on physical, emotional, cognitive, social and role subjects availability, three more syndromes (Fatigue, Pain and Nausea/Vomit), quality of life(QOL) will be evaluated by GLM statistics. In addition, in case of lung cancer, 13 questions will be asked by the EORTC QLQ-C13 forms. As the assessment of endpoints for efficacy to reduce side effects induced by chemotherapy and radiotherapy, the data of image scanning and hemato-urinalysis can be usefully applied on immune response, weight loss, indigestion, hemopoietic damage and injury of liver and kidney, while the changes of syndromes of side effect can be evaluated by differentiation methods of Qi and blood and five viscera. However, it is still necessary to determine the ratio between scientific analytical method and Oriental differentiation method as well as confirm the Oriental assessment endpoints by clinical trial. In addition, we suggest the continuous development of assessment endpoints on other carcinomas except of hepatocelluar carcinoma and lung cancer in future.

A Comparison between Water and Ethanol Extracts of Rumex acetosa for Protective Effects on Gastric Ulcers in Mice

  • Bae, Ji-Yeong;Lee, Yoon-Seok;Han, Sun-Young;Jeong, Eun-Ju;Lee, Mi-Kyeong;Kong, Jae-Yang;Lee, Dong-Hoon;Cho, Kyeong-Jae;Lee, Haeng-Soon;Ahn, Mi-Jeong
    • Biomolecules & Therapeutics
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    • v.20 no.4
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    • pp.425-430
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    • 2012
  • Rumex acetosa is a perennial herb that is widely distributed across eastern Asia. Although the hot water extract of R. acetosa has been used to treat gastritis or gastric ulcers as a folk medicine, no scientific report exists for the use of this plant to treat gastric ulcers. Hence, the present study was undertaken to assess the anti-ulcer activity of water and 70% ethanol extracts obtained from R. acetosa, using an HCl/ethanol-induced gastric ulcer model in mice. Anti-inflammatory and free radical-scavenging activities of these two extracts were also evaluated and compared. As a result, the administration of R. acetosa extracts significantly reduced the occurrence of gastric ulcers. However, significant differences in protective activity against gastric ulcers were observed between the two samples. In the case of the group pretreated with an ethanol extract dosage of 100 mg/kg, the protective effect (90.9%) was higher than that of water extract (41.2%). Under histological evaluation, pretreatment with R. acetosa extracts reversed negative effects, such as inflammation, edema, moderate hemorrhaging and loss of epithelial cells, presented by HCl/ethanol-treated stomachs. Meanwhile, R. acetosa extracts showed potent DPPH radical-scavenging activity and decreased NO production in a murine macrophage cell line, RAW 264.7, in a dose-dependent manner without affecting cellular viability. The greater anti-ulcer and NO production inhibitory activities exhibited by ethanol extracts compared to water extracts could be ascribed to the higher emodin levels, a major anthraquinone component of this plant.

The Effect of Jeju Wild Ginseng Extracts on Skin Barrier via Serine-Palmitoyltransferase (제주산양산삼이 세린-팔미토일 전이효소(Serine-Palmitoyltransferase)를 통해 피부 장벽에 미치는 효과에 대한 연구)

  • Kim, Hyo Min;Lee, Jung No;Kim, Jae Moon;Kim, Sung Kyu;Park, Sung-Min
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.2
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    • pp.119-126
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    • 2016
  • Skin is the largest organ that protects the body from the external environmental factors such as smog, cigarette smoke, UV. Protective skin barrier is composed with keratinizational keratinocytes and intercellular lipids such as ceramides, cholesterols and fatty acids combined by the lamellar liquid crystal structure. In this research, we confirmed that the Jeju wild ginseng (JWG) extracts dose-dependently increased the expression of serine-palmitoyltransferase (SPT) protein which is associated with ceramide biosynthesis. In addition, emulsion containing 5% JWG extract was applied on skin of human volunteers for 2 weeks and then significantly reduced transepidermal water loss (TEWL) compared to that of control group. As a results, JWG extract increased the biosynthesis of ceramides that is the key components of the skin lipid through enhancing expression of SPT. In addition, JWG extract reduced TEWL resulting in improvement of skin barrier function. In this context, we suggest that JWG extract could be used as a skin barrier enhancer and moisturing agents in cosmetic fileds.

The effects of zoledronic acid on the progression of experimental periodontitis in rats: histological and microtomographic analyses

  • de Marcelos, Priscylla Goncalves Correia Leite;da Cruz Perez, Danyel Elias;Soares, Diego Moura;de Araujo, Samuel Silva;Evencio, Liriane Baratella;Pontual, Maria Luiza dos Anjos;Ramos-Perez, Flavia Maria de Moraes
    • Journal of Periodontal and Implant Science
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    • v.51 no.4
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    • pp.264-275
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    • 2021
  • Purpose: Periodontitis is considered a local risk factor for medication-related osteonecrosis of the jaws (MRONJ). However, little is known about the progression of periodontitis in the presence of zoledronic acid (ZOL). The aim of this study was to evaluate the effects of the systemic use of ZOL on the progression of experimental periodontitis (EP) in rats, as ZOL could modulate the progression of periodontitis and concomitantly cause MRONJ in individuals with periodontitis. Methods: Forty-eight male Wistar rats were randomly distributed in 6 groups (n=8 each). To induce EP, ligatures were placed around the right first mandibular molars. Three groups were treated with ZOL (0.15 mg/kg/week, intraperitoneal), and 3 with 0.9% saline solution (controls). In the ZOL/Lig30 and ZOL/Lig 15 groups, after 4 weeks of treatment with ZOL, EP was induced and euthanasia was performed after 30 and 15 days of EP induction, respectively. In both groups, the animals continued to receive ZOL after EP until the end of the experiment. In the Lig/ZOL group, EP was induced first, and 15 days later, ZOL was administered for 8 weeks, with euthanasia 1 week after the last dose. After euthanasia, the mandibles were evaluated using micro-computed microtomography (micro-CT) and histomorphometry. Bone loss was measured, and the presence of osteonecrosis was evaluated histologically. The data were evaluated using the Student t-test and the Mann-Whitney test, with a significance level of 5%. Results: In the Lig/ZOL group, micro-CT revealed less alveolar bone resorption in the distal root (P<0.01) than in the control group (Lig/Con). Histomorphometric analysis confirmed less alveolar bone resorption in the Lig/ZOL group (P=0.001). Histologically, osteonecrosis was more common in the ZOL groups. Conclusion: ZOL decreased alveolar bone resorption in rats with EP. However, it presented a higher risk for MRONJ.

Intraoperative Neurophysiological Monitoring and Neuromuscular Anesthesia Depth Monitoring (수술 중 신경계 추적 감시 검사와 근 이완 마취 심도의 측정)

  • Kim, Sang-Hun;Park, Soon-Bu;Kang, Hyo-Chan;Park, Sang-Ku
    • Korean Journal of Clinical Laboratory Science
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    • v.52 no.4
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    • pp.317-326
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    • 2020
  • Deep blocking of consciousness alone does not prevent a reaction to severe stimuli, and copious amounts of pain medication do not guarantee unconsciousness. Therefore, anesthesia must satisfy both: the loss of consciousness as well as muscle relaxation. Muscle relaxants improve the intra-bronchial intubation, surgical field of vision, and operating conditions, while simultaneously reducing the dose of inhalation or intravenous anesthesia. Muscle relaxants are also very important for breathing management during controlled mechanical ventilation during surgery. Excessive dosage of such muscle relaxants may therefore affect neurological examinations during surgery, but an insufficient dosage will result in movement of the patient during the procedure. Hence, muscle relaxation anesthesia depth and neurophysiological monitoring during surgery are closely related. Using excessive muscle relaxants is disadvantageous, since neurophysiological examinations during surgery could be hindered, and eliminating the effects of complete muscle relaxation after surgery is challenging. In the operation of neurophysiological monitoring during the operation, the anesthesiologist administers muscle relaxant based on what standard, it is hoped that the examination will be performed more smoothly by examining the trends in the world as well as domestic and global trends in maintaining muscle relaxant.

Artifact Reduction in Sparse-view Computed Tomography Image using Residual Learning Combined with Wavelet Transformation (Wavelet 변환과 결합한 잔차 학습을 이용한 희박뷰 전산화단층영상의 인공물 감소)

  • Lee, Seungwan
    • Journal of the Korean Society of Radiology
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    • v.16 no.3
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    • pp.295-302
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    • 2022
  • Sparse-view computed tomography (CT) imaging technique is able to reduce radiation dose, ensure the uniformity of image characteristics among projections and suppress noise. However, the reconstructed images obtained by the sparse-view CT imaging technique suffer from severe artifacts, resulting in the distortion of image quality and internal structures. In this study, we proposed a convolutional neural network (CNN) with wavelet transformation and residual learning for reducing artifacts in sparse-view CT image, and the performance of the trained model was quantitatively analyzed. The CNN consisted of wavelet transformation, convolutional and inverse wavelet transformation layers, and input and output images were configured as sparse-view CT images and residual images, respectively. For training the CNN, the loss function was calculated by using mean squared error (MSE), and the Adam function was used as an optimizer. Result images were obtained by subtracting the residual images, which were predicted by the trained model, from sparse-view CT images. The quantitative accuracy of the result images were measured in terms of peak signal-to-noise ratio (PSNR) and structural similarity (SSIM). The results showed that the trained model is able to improve the spatial resolution of the result images as well as reduce artifacts in sparse-view CT images effectively. Also, the trained model increased the PSNR and SSIM by 8.18% and 19.71% in comparison to the imaging model trained without wavelet transformation and residual learning, respectively. Therefore, the imaging model proposed in this study can restore the image quality of sparse-view CT image by reducing artifacts, improving spatial resolution and quantitative accuracy.

Hepatoprotective Effects of Hovenia dulcis Extract on Acute and Chronic Liver Injuries induced by Alcohol and Carbon Tetrachloride (알코올 및 사염화탄소에 의해 유발된 급만성 간손상에 대한 지구자 열수추출물의 보호효과)

  • Kim, Young-Sik;Park, Juyeon;Kwon, Yongbeom;Lim, Dong Wook;Song, MiKyung;Choi, Ho-Young;Kim, Hocheol
    • The Korea Journal of Herbology
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    • v.28 no.4
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    • pp.25-32
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    • 2013
  • Objectives : The purpose of this study was to evaluate the hepatoprotective effect of Hovenia dulcis extract on acute and chronic liver injuries induced by alcohol and $CCl_4$ in mice and rats. Methods : In acute alcohol-induced liver injury, mice were administered Hovenia dulcis extracts (60 and 200 mg/kg) orally before and after alcohol administration. In chronic alcohol-induced liver injury, mice were administered alcohol containing liquid diet for 4 weeks. The mice were administered H. dulcis extracts (60 and 200 mg/kg) mixed with the liquid diet. In acute $CCl_4$-induced liver injury, rats received a single dose of $CCl_4$ (2 mL/kg in olive oil, intraperitoneally). Rats were administered H. dulcis extracts (30, 100 and 300 mg/kg) before and after $CCl_4$ administrations. After the ends of the administrations, the serum levels of AST and ALT were measured using chemical analyzer, and ${\gamma}$-GTP levels were measured using spectrophotometer. Results : In acute alcohol-induced liver injury, H. dulcis extracts treated group showed significant reduction in ALT levels compared to those of control group. In chronic alcohol-induced liver injury, it inhibited weight-loss compared to normal group and showed significant reduction in AST, ALT and ${\gamma}$-GTP levels compared to control group. In acute $CCl_4$-induced liver injury, it also showed significant reduction in AST, ALT levels compared to control group. Conclusions : The results show that H. dulcis extract has hepatoprotective effect in acute and chronic alcohol-induced liver injury and acute $CCl_4$-induced liver injury. These findings suggest that H. dulcis could be a potent hepatoprotective agent.

Phosphodiesterase-5 Inhibitor Attenuates Anxious Phenotypes and Movement Disorder Induced by Mild Ischemic Stroke in Rats

  • Yu, Yeon Hee;Kim, Seong-Wook;Kang, Juhyeon;Song, Yejin;Im, yHyuna;Kim, Seo Jeong;Yoo, Dae Young;Lee, Man-Ryul;Park, Dae-Kyoon;Oh, Jae Sang;Kim, Duk-Soo
    • Journal of Korean Neurosurgical Society
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    • v.65 no.5
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    • pp.665-679
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    • 2022
  • Objective : Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil (SIL), a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects. In this study, we investigated the efficacy of PDE5i in the emotional and behavioral abnormalities in rats with mild ischemic stroke. Methods : We divided the rats into four groups as follows (n=20, respectively) : group 1, naïve; group 2, middle cerebral artery occlusion (MCAo30); group 3, MCAo30+SIL-pre; and group 4, MCAo30+SIL-post. In the case of drug administration groups, single dose of PDE5i (sildenafil citrate, 20 mg/kg) was given at 30-minute before and after reperfusion of MCAo in rats. After surgery, we investigated and confirmed the therapeutic effect of sildenafil on histology, immunofluorescence, behavioral assays and neural oscillations. Results : Sildenafil alleviated a neuronal loss and reduced the infarction volume. And results of behavior task and immunofluorescence shown possibility that anti-inflammation process and improve motor deficits sildenafil treatment after mild ischemic stroke. Furthermore, sildenafil treatment attenuated the alteration of theta-frequency rhythm in the CA1 region of the hippocampus, a known neural oscillatory marker for anxiety disorder in rodents, induced by mild ischemic stroke. Conclusion : PDE5i as effective therapeutic agents for anxiety and movement disorders and provide robust preclinical evidence to support the development and use of PDE5i for the treatment of mild ischemic stroke residual disorders.

Hair Growth Effect of TS-SCLF from Schisandra chinensis Extract Fermented with Lactobacillus plantarum

  • Young Min, Woo;Jae Yong, Seo;Soo-ya, Kim;Ji Hyun, Cha;Hyun Dae, Cho;Young Kwon, Cha;Ju Tae, Jeong;Sung Min, Park;Hwa Sun, Ryu;Jae Mun, Kim;Moon Hoy, Kim;Hee-Taek, Kim;Yong-Min, Kim;Kwang Sik, Joo;Sun Mi, Lee;JungNo, Lee;Andre, Kim
    • Microbiology and Biotechnology Letters
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    • v.50 no.4
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    • pp.533-547
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    • 2022
  • This study investigated the hair growth effect of Schisandra chinensis extract (TS-SC) and TS-SC fermented by Lactobacillus plantarum (TS-SCLF) on human dermal papilla cells (hDPCs). The production of vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), keratinocyte growth factor/fibroblast growth factor 7 (KGF/FGF-7) and hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGF-β1) were examined. The secretion rates of VEGF and KGF/FGF-7 were high in TS-SC, and the secretion rates of IGF-1 and HGF were high in TS-SCLF. TGF-β1 was inhibited in a concentration-dependent manner in all samples. Gene expression of VEGF, IGF-1, KGF, HGF and alkaline phosphatase, relevant to hair growth, were examined. The data revealed that TS-SC and TS-SCLF successfully promoted hair growth in hDPCs. The IGF-1 gene was expressed in a dose-dependent manner in TS-SCLF. These results indicate that TS-SC and TS-SCLF fermented extract effectively promoted hair growth and gene expression relevant to hair growth in hDPCs. Used in clinical trials the test substance 'CMK-LPF01' showed a statistically significant increase in the number of hairs at 8 weeks, 16 weeks, and 24 weeks compared to before product use, and a change in hair growth, a secondary efficacy evaluation variable. Through additional research in the future, it is expected that "CMK-LPF01" can be developed as a functional material that can help alleviate symptoms of hair loss.

Neuroprotective Effects of Bunsimgieum (분심기음(分心氣飮)의 도파민 세포 보호 효과)

  • Kim, Ro-Sa;Lee, Chang-Hoon;Lee, Jin-Moo;Cho, Jung-Hoon;Jang, Jun-Bock;Lee, Kyung-Sub
    • The Journal of Korean Obstetrics and Gynecology
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    • v.22 no.2
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    • pp.119-131
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    • 2009
  • Purpose: The depression accompanied with menopuase shows the relation with the dopamine secretion. These studies were undertaken to evaluate the anti- oxidative and neuroprotective effects of Bunsimgieum(BSGE) on dopaminergic neurons. Methods: To estimate the antioxidant effects, we carried out 1.1-diphenyl-2- picrylhydrazyl (DPPH) free radical scavenging assay, 2,2'-azinobis-(3-ethylbenzothiazoline -6-sulfonic acid (ABTS) radical cation decolorization assay, and measurement of total polyphenolic content. To evaluate neuroprotective effect of BSGE in vitro, We performed thiazolyl blue tetrazolium bromide (MTT) assay, reactive oxygen species (ROS) creation in SH-SY5Y. Tyrosine hydroxylase (TH) immunocytochemistry, nitric oxide (NO) assay, and TNF-${\alpha}$ assay in primary rat mesencephalic dopaminergic neurons. Results: The DPPH free radical and the ABTS radical cation inhibition activities were increased at a dose dependent manner. Total polyphenolic content was 0.83%. In SH-SY5Y culture, BSGE significantly increased the decreased cell viability by 6-OHDA at the concentrations of 10${\mu}$g/m${\ell}$ in pre-treatment group, 0.1-200${\mu}$g/m${\ell}$ in post-treatment group. The production of ROS induced by 6-OHDA was significantly inhibited in BSGE treated group. In mesencephalic dopaminergic cell culture, the BSGE group reduced the dopaminergic cell loss against 6-OHDA toxicity and the production of No and TNF-${\alpha}$ at the concentration of 5${\mu}$g/m${\ell}$. Conclusion: These results shows that BSGE has antioxidant and neuroprotective effects in the dopaminergic cells through decreasing the production of ROS, NO and TNF-${\alpha}$ which can cause many neurodegenerative changes in brain cell. We suggest that BSGE could be useful for the treatment of postmenopausal depression related with the decrease of dopamine.