• Title/Summary/Keyword: Pre-clinical strategy

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Multi-parametric MRIs based assessment of Hepatocellular Carcinoma Differentiation with Multi-scale ResNet

  • Jia, Xibin;Xiao, Yujie;Yang, Dawei;Yang, Zhenghan;Lu, Chen
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.13 no.10
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    • pp.5179-5196
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    • 2019
  • To explore an effective non-invasion medical imaging diagnostics approach for hepatocellular carcinoma (HCC), we propose a method based on adopting the multiple technologies with the multi-parametric data fusion, transfer learning, and multi-scale deep feature extraction. Firstly, to make full use of complementary and enhancing the contribution of different modalities viz. multi-parametric MRI images in the lesion diagnosis, we propose a data-level fusion strategy. Secondly, based on the fusion data as the input, the multi-scale residual neural network with SPP (Spatial Pyramid Pooling) is utilized for the discriminative feature representation learning. Thirdly, to mitigate the impact of the lack of training samples, we do the pre-training of the proposed multi-scale residual neural network model on the natural image dataset and the fine-tuning with the chosen multi-parametric MRI images as complementary data. The comparative experiment results on the dataset from the clinical cases show that our proposed approach by employing the multiple strategies achieves the highest accuracy of 0.847±0.023 in the classification problem on the HCC differentiation. In the problem of discriminating the HCC lesion from the non-tumor area, we achieve a good performance with accuracy, sensitivity, specificity and AUC (area under the ROC curve) being 0.981±0.002, 0.981±0.002, 0.991±0.007 and 0.999±0.0008, respectively.

Commonly Used Surfactant, Tween 80, Improves Absorption of P-Glycoprotein Substrate, Digoxin, in Rats

  • Zhang, Hongjian;Yao, Ming;Morrison, Richard-A.;Chong, Sae-Ho
    • Archives of Pharmacal Research
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    • v.26 no.9
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    • pp.768-772
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    • 2003
  • Tween 80 (Polysorbate 80) is a hydrophilic nonionic surfactant commonly used as an ingredient in dosing vehicles for pre-clinical in vivo studies (e.g., pharmacokinetic studies, etc.). Tween 80 increased apical to basolateral permeability of digoxin in Caco-2 cells suggesting that Tween 80 is an in vitro inhibitor of P-gp. The overall objective of the present study was to investigate whether an inhibition of P-gp by Tween 80 can potentially influence in vivo absorption of P-gp substrates by evaluating the effect of Tween 80 on the disposition of digoxin (a model P-gp substrate with minimum metabolism) after oral administration in rats. Rats were dosed orally with digoxin (0.2 mg/kg) formulated in ethanol (40%, v/v) and saline mixture with and without Tween 80 (1 or 10%, v/v). Digoxin oral AUC increased 30 and 61% when dosed in 1 % and 10% Tween 80, respectively, compared to control (P<0.05). To further examine whether the increase in digoxin AUC after oral administration of Tween 80 is due, in part, to a systemic inhibition of digoxin excretion in addition to an inhibition of P-gp in the GI tract, a separate group of rats received digoxin intravenously (0.2 mg/kg) and Tween 80 (10% v/v) orally. No significant changes in digoxin IV AUC was noted when Tween 80 was administered orally. In conclusion, Tween 80 significantly increased digoxin AUC and Cmax after oral administration, and the increased AUC is likely to be due to an inhibition of P-gp in the gut (i.e., improved absorption). Therefore, Tween 80 is likely to improve systemic exposure of P-gp substrates after oral administration. Comparing AUC after oral administration with and without Tween 80 may be a viable strategy in evaluating whether oral absorption of P-gp substrates is potentially limited by P-gp in the gut.

Protective Effects of Individual Extract and Mixture of Forsythia Fructus and Corydalis Tuber on Chronic Pancreatitis in Mice (마우스 만성 췌장염 모델에서 연교(連翹)와 현호색(玄胡索) 단일 추출물 및 추출 혼합물의 보호 효과)

  • Shin, Joon Yeon;Choi, Ji-Won;Kim, Dong-Uk;Zhou, Ziqi;Kweon, Bitna;Bae, Gi-Sang;Song, Ho-Joon;Park, Sung-Joo
    • The Korea Journal of Herbology
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    • v.36 no.1
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    • pp.59-66
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    • 2021
  • Objectives : Forsythiae Fructus has been reported to have anti-inflammatory effects in many diseases, and Corydalis Tuber has been used as a pain suppressor in Eastern Asia. However, the protective effects of individual water extract of Forsythiae Fructus (FF) and Corydalis Tuber (CT) and the mixture of FF and CT (FC) on chronic pancreatitis (CP) were not well-investigated. Therefore, we investigated the protective effects of FF, CT, and FC on CP in mice. Methods : To induce CP, cerulein was injected 6 times a day, 4 times a week for 3 weeks. 1 h before the every cerulein injection, 200 mg/kg of FF, CT, or FC was intraperitoneally injected to mice. Histological analysis of pancreas was examined by hematoxylin and eosin stain and collagen deposition was examined by Masson's trichrome stain. Fibrogenic parameters such as α-smooth muscle actin (α-SMA), extracellular matrix (ECM) deposition, and fibrotic cytokines such as transforming growth factor (TGF)-β1 and platelet-derived growth factor (PDGF) were also analyzed by immunofluorescence stain and real-time PCR. Results : Histological damages in pancreas were inhibited by pre-treatment of FF or FC but not CT. α-SMA and ECM in pancreas were inhibited by pre-treatment of CT or FC but not FF. Moreover, the expression of TGF-β1 and PDGF in pancreas were inhibited by FF, CT or FC. Conclusions : Our results suggest that FC have protective effect on CP in mice through inhibition of α-SMA, ECM, TGF-β1 and PDGF in pancreas, and these findings could suggest new clinical strategy for CP.

Development and Evaluation of Patient Safety Reporting Promoting Education Program (환자안전보고 촉진 교육프로그램의 개발 및 평가)

  • Kim, Myoung-Soo;Kim, Yun-Hee
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.13 no.1
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    • pp.284-295
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    • 2012
  • The purpose of this study was to develop and evaluate patient safety reporting promoting strategy for nurses to improve nursing care quality. The process included three phase - construction, implementation and evaluation phase. Before the construction phase has two kinds of subcategories as analysis and verification. Analysis phase was consisted of literature review and field study, and verification was conducted by two specialist. At the construction phase, patient safety reporting system, educational materials, planning for public relation, and reward preparation were developed. After implementation during 12 weeks, we evaluated pre-post scores of satisfaction, stress of conscience, job performances. The participants were 51 nurses working for a hospitals. The program was developed and then administered to the experimental group for 12 weeks. One group pretest-posttest design was used for this study. Data were analyzed using descriptive analysis, paired t-test with the SPSS WIN 18.0 program. After the intervention, job performance scores improved significantly from 3.62 to 3.75(t=2.653, p=.009). But job stress didn't changed significantly(t=.785, p=.434). These strategy can be applied to many clinical setting that will be helpful to promote patient safety reporting for nurses.

Clinical Comparison of Low-dose and High-dose Steroid in Pediatric Cardiac Surgery with Cardiopulmonary Bypass

  • Choi Seok-Cheol;Kim Song-Myung;Kim Yang-Weon
    • Biomedical Science Letters
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    • v.12 no.3
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    • pp.289-301
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    • 2006
  • Cardiopulmonary bypass (CPB) for cardiac surgery triggers the production and release of numerous chemotactic substances and cytokines, ensuing systemic inflammatory response that leads to postoperative major organ dysfunction. Traditionally, corticosteroids (steroid) have been administered to patients undergoing cardiac surgery to ward off these detrimental physiologic alterations. However, the majority of the studies have been performed on adult patients with high-dose steroid. We carried out a randomized, prospective, double-blind study to compare the efficacy of low-dose steroid with that of high-dose steroid and to determine the adequate dose of pretreated-steroid for prophylactic effects in pediatric cardiac surgery. Thirty pediatric patients scheduled for elective cardiac surgery were randomly assigned to two groups; fifteen patients received low-dose methylprednisolone (10mg/kg intravenously, n=15, low-dose group) and the others received high-dose methylprednisolone (30mg/kg intravenously, n=15, high-dose group) 1 hour prior to CPB. Arterial blood samples were taken before CPB (Pre-CPB), 10 minutes after start of CPB (CPB-10), and immediately after CPB-end (CPB-OFF) for measuring total leukocyte counts (T-WBC) and diff-counts, platelet counts, interleukin-6 (IL-6), myeloperoxidase (MPO), total antioxidant (TAO), neuron-specific enolase (NSE), troponin I (TNI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and blood urea nitrogen (BUN) levels. Other parameters such as volumes of urine output, pulmonary index $(PI,\;PaO_2/FiO_2)$, mechanical ventilating period, intensive care unit (ICU)-staying period, postoperative complications (fever, wound problem), postoperative 24 hrs and total volumes in blood loss, and hospitalized days were also assessed. All parameters were compared between two groups. There were no significant differences in T-WBC counts, monocyte fraction, platelet counts, TA levels, NSE levels, creatinine levels, BUN levels, the volumes of total urine output, PI, the incidences of fever and wound problem, postoperative 24hrs- and total-blood loss volumes and ICU-staying period between two groups (P>0.05). At CPB-OFF, neutrophil fraction, MPO level, TNI level, and AST level were higher in the high-dose group than in the low-dose group (P<0.05). IL-6 level at CPB-10 was higher in the high dose-group than in the low-dose group (P<0.05). Furthermore, mechanical ventilating periods and hospitalized days of the high-dose group were significantly longer than those of low-dose group (P<0.05). The high-dose group had significantly low lymphocyte fi-action at CPB-OFF compared with the low-dose group (P<0.001). These findings suggest that pretreatment of high-dose steroid is not superior to that of low-dose steroid regrading its potential benefits in pediatric cardiac surgery. Therefore, the conventional strategy of steroid treatment, high-dose pretreatment, should be modified in the cardiac surgery with CPB. However, further studies must be performed on the larger number of patients in as much as small number of patients in this study.

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Treat-to-Target Strategy for Asian Patients with Early Rheumatoid Arthritis: Result of a Multicenter Trial in Korea

  • Song, Jason Jungsik;Song, Yeong Wook;Bae, Sang Cheol;Cha, Hoon-Suk;Choe, Jung-Yoon;Choi, Sung Jae;Kim, Hyun Ah;Kim, Jinseok;Kim, Sung-Soo;Lee, Choong-Ki;Lee, Jisoo;Lee, Sang-Heon;Lee, Shin-Seok;Lee, Soo-Kon;Lee, Sung Won;Park, Sung-Hwan;Park, Won;Shim, Seung Cheol;Suh, Chang-Hee;Yoo, Bin;Yoo, Dae-Hyun;Yoo, Wan-Hee
    • Journal of Korean Medical Science
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    • v.33 no.52
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    • pp.346.1-346.11
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    • 2018
  • Background: To evaluate the therapeutic benefits of the treat-to-target (T2T) strategy for Asian patients with early rheumatoid arthritis (RA) in Korea. Methods: In a 1-year, multicenter, open-label strategy trial, 346 patients with early RA were recruited from 20 institutions across Korea and stratified into 2 groups, depending on whether they were recruited by rheumatologists who have adopted the T2T strategy (T2T group) or by rheumatologists who provided usual care (non-T2T group). Data regarding demographics, rheumatoid factor titer, anti-cyclic citrullinated peptide antibody titer, disease activity score of 28 joints (DAS28), and Korean Health Assessment Questionnaire (KHAQ) score were obtained at baseline and after 1 year of treatment. In the T2T group, the prescription for disease-modifying antirheumatic drugs was tailored to the predefined treatment target in each patient, namely remission (DAS28 < 2.6) or low disease activity (LDA) ($2.6{\leq}DAS28$ < 3.2). Results: Data were available for 163 T2T patients and 162 non-T2T patients. At the end of the study period, clinical outcomes were better in the T2T group than in the non-T2T group (LDA or remission, 59.5% vs. 35.8%; P < 0.001; remission, 43.6% vs. 19.8%; P < 0.001). Compared with non-T2T, T2T was also associated with higher rate of good European League Against Rheumatism response (63.0% vs. 39.8%; P < 0.001), improved KHAQ scores (-0.38 vs. -0.13; P = 0.008), and higher frequency of follow-up visits (5.0 vs. 2.0 visits/year; P < 0.001). Conclusion: In Asian patients with early RA, T2T improves disease activity and physical function. Setting a pre-defined treatment target in terms of DAS28 is recommended.

Factors to Predict Successful Harvest during Autologous Peripheral Hematopoietic Stem Cell Collection

  • Kim, Mun-Ja;Jin, Soo-He;Lee, Duk-Hee;Park, Dae-Weon;Koh, Sung-Ae;Lee, Kyung-Hee;Hyun, Myung-Soo;Kim, Min-Kyoung
    • Biomedical Science Letters
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    • v.18 no.2
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    • pp.131-138
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    • 2012
  • Autologous peripheral blood stem cell transplantation (PBSCT) has been used as a major treatment strategy for hematological malignancies. The number of CD34 positive cells in the harvested product is a very important factor for achieving successful transplantation. We studied the factors that can predict the number of CD34 positive cells in the harvested product of acute myelocytic leukemia (AML), multiple myeloma (MM) and Non-Hodgkin's lymphoma (NHL) patients after mobilizing them with chemotherapy plus G-CSF. A total of 73 patients (AML 19 patients, MM 28 patients, NHL 26 patients) with hematological malignancies had been mobilized with chemotherapy and granulocyte colony-stimulating growth factor from April, 2000 to February, 2012. Group's characteristics, checkup opinion of pre-peripheral blood on the day of harvest & outcome of PBSC were analyzed and evaluated using SPSS statistics program after grouping patients as below; group 1: CD34 cell counts < $2{\times}10^6/kg$ (n=16); group 2: $2{\times}10^6/kg{\leq}CD34$ cell counts < $6{\times}10^6/kg$ (n=32); group 3: CD34 cell counts ${\geq}6{\times}10^6/kg$ (n=25). We analyzed the clinical characteristics, the peripheral blood (PB) parameters and the number of CD34 positive cells in the PB and their correlation with the yield of CD34 positive cells collected from the mobilized patients. The total number of leukapheresis sessions was 263 (mean: 3.55 session per patient), and the mean number of harvested CD34 positive cells per patient was $7.37{\times}10^6/kg$. The number of CD34 positive cells in product was significantly correlated with the number of platelet and CD34 positive cells in peripheral blood (P<0.05). The number of PB CD34 positive cells was the best significant factor for the quantity of harvested CD34 positive cells on the linear regression analysis (P<0.05). Many factors could influence the mobilization of peripheral blood stem cells. Platelet count and PB CD34 positive cells count were the two variables which remained to be significant in multivariate analysis. Therefore, the number of platelet and CD34 positive cells in peripheral blood on the day of harvest can be used as an accurate predictor for successful peripheral blood stem cell collection.

Upregulation of Carbonyl Reductase 1 by Nrf2 as a Potential Therapeutic Intervention for Ischemia/Reperfusion Injury during Liver Transplantation

  • Kwon, Jae Hyun;Lee, Jooyoung;Kim, Jiye;Kirchner, Varvara A.;Jo, Yong Hwa;Miura, Takeshi;Kim, Nayoung;Song, Gi-Won;Hwang, Shin;Lee, Sung-Gyu;Yoon, Young-In;Tak, Eunyoung
    • Molecules and Cells
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    • v.42 no.9
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    • pp.672-685
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    • 2019
  • Currently, liver transplantation is the only available remedy for patients with end-stage liver disease. Conservation of transplanted liver graft is the most important issue as it directly related to patient survival. Carbonyl reductase 1 (CBR1) protects cells against oxidative stress and cell death by inactivating cellular membrane-derived lipid aldehydes. Ischemia-reperfusion (I/R) injury during living-donor liver transplantation is known to form reactive oxygen species. Thus, the objective of this study was to investigate whether CBR1 transcription might be increased during liver I/R injury and whether such increase might protect liver against I/R injury. Our results revealed that transcription factor Nrf2 could induce CBR1 transcription in liver of mice during I/R. Pre-treatment with sulforaphane, an activator of Nrf2, increased CBR1 expression, decreased liver enzymes such as aspartate aminotransferase and alanine transaminase, and reduced I/R-related pathological changes. Using oxygen-glucose deprivation and recovery model of human normal liver cell line, it was found that oxidative stress markers and lipid peroxidation products were significantly lowered in cells overexpressing CBR1. Conversely, CBR1 knockdown cells expressed elevated levels of oxidative stress proteins compared to the parental cell line. We also observed that Nrf2 and CBR1 were overexpressed during liver transplantation in clinical samples. These results suggest that CBR1 expression during liver I/R injury is regulated by transcription factor Nrf2. In addition, CBR1 can reduce free radicals and prevent lipid peroxidation. Taken together, CBR1 induction might be a therapeutic strategy for relieving liver I/R injury during liver transplantation.