• Title/Summary/Keyword: Systemic Model

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Chemical Risk Assessment Screening Tool of a Global Chemical Company

  • Tjoe-Nij, Evelyn;Rochin, Christophe;Berne, Nathalie;Sassi, Alessandro;Leplay, Antoine
    • Safety and Health at Work
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    • v.9 no.1
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    • pp.84-94
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    • 2018
  • Background: This paper describes a simple-to-use and reliable screening tool called Critical Task Exposure Screening (CTES), developed by a chemical company. The tool assesses if the exposure to a chemical for a task is likely to be within acceptable levels. Methods: CTES is a Microsoft Excel tool, where the inhalation risk score is calculated by relating the exposure estimate to the corresponding occupational exposure limit (OEL) or occupational exposure band (OEB). The inhalation exposure is estimated for tasks by preassigned ART1.5 activity classes and modifying factors. Results: CTES requires few inputs. The toxicological data, including OELs, OEBs, and vapor pressure are read from a database. Once the substance is selected, the user specifies its concentration and then chooses the task description and its duration. CTES has three outputs that may trigger follow-up: (1) inhalation risk score; (2) identification of the skin hazard with the skin warnings for local and systemic adverse effects; and (3) status for carcinogenic, mutagenic, or reprotoxic effects. Conclusion: The tool provides an effective way to rapidly screen low-concern tasks, and quickly identifies certain tasks involving substances that will need further review with, nevertheless, the appropriate conservatism. This tool shows that the higher-tier ART1.5 inhalation exposure assessment model can be included effectively in a screening tool. After 2 years of worldwide extensive use within the company, CTES is well perceived by the users, including the shop floor management, and it fulfills its target of screening tool.

Expression of prune dwarf Ilarvirus coat protein sequences in Nicotiana benthamiana plants interferes with PDV systemic proliferation

  • Raquel, Helena;Lourenco, Tiago;Moita, Catarina;Oliveira, M. Margarida
    • Plant Biotechnology Reports
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    • v.2 no.1
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    • pp.75-85
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    • 2008
  • Prune dwarf virus (PDV) is an Ilarvirus systemically infecting almond trees and other Prunus species and spreading through pollen, among other means. We have studied strategies based on coat protein (cp) gene to block PDV replication in host plant cells. A Portuguese isolate of PDV was obtained from infected almond leaves and used to produce the cDNA of the cp gene. Various constructs were prepared based on this sequence, aiming for the transgenic expression of the original or modified PDV coat protein (cpPDVSense and cpPDVMutated) or for the expression of cpPDV RNA (cpPDVAntisense and cpPDVwithout start codon). All constructs were tested in a PDV host model, Nicotiana benthamiana, and extensive molecular characterization and controlled infections were performed on transformants and their progenies. Transgenic plants expressing the coat protein RNA were able to block the proliferation of a PDV isolate sharing only 91% homology with the isolate used for cpPDV cloning, as evaluated by DAS-ELISA on newly developed leaves. With cp expression, the blockage of PDV proliferation in newly developed leaves was only achieved with the construct cpPDV Mutated, where the coat protein has a substitution in the 14th aa residue, with arginine replaced by alanine. This result points to a possible role of the mutated amino acid in the virus ability to replicate and proliferate. This work reveals the possibility of achieving protection against PDV through either coat protein RNA or mutated cp sequence.

Anti-inflammatory and anti-diabetic effects of brown seaweeds in high-fat diet-induced obese mice

  • Oh, Ji-Hyun;Kim, Jaehoon;Lee, Yunkyoung
    • Nutrition Research and Practice
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    • v.10 no.1
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    • pp.42-48
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    • 2016
  • BACKGROUND/OBJECTIVES: Seaweeds have been reported to have various health beneficial effects. In this study, we investigated the potential anti-obesity and anti-inflammatory effects of four types of domestic brown seaweeds in a high-fat diet-induced obese mouse model and bone marrow-derived macrophages (BMDM). MATERIALS/METHODS: Male C57BL/6N mice were fed low-fat diet (LFD), high-fat diet (HFD) or HFD containing Undaria Pinnatifida, HFD containing Laminaria Japonica (LJ), HFD containing Sargassum Fulvellum, or HFD containing Hizikia Fusiforme (HF) for 16 weeks. RESULTS: Brown seaweed supplementation did not affect long-term HFD-associated changes in body weight or adiposity, although mice fed HFD + LJ or HFD + HF gained slightly less body weight compared with those fed HFD at the beginning of feeding. Despite being obese, mice fed HFD + LJ appeared to show improved insulin sensitivity compared to mice fed HFD. Consistently, we observed significantly reduced blood glucose concentrations in mice fed HFD + LJ compared with those of mice fed HFD. Although no significant differences in adipocyte size were detected among the HFD-fed groups, consumption of seaweeds decreased formation of HFD-induced crown-like structures in gonadal adipose tissue as well as plasma inflammatory cytokines. BMDM from mice fed HFDs with seaweeds showed differential regulation of pro-inflammatory cytokines such as IL-$1{\beta}$ and IL-6 compared with BMDM from mice fed HFD by LPS stimulation. CONCLUSION: Although seaweed consumption did not prevent long-term HFD-induced obesity in C57BL/6N mice, it reduced insulin resistance (IR) and circulation of pro-inflammatory cytokines. Therefore, seaweeds may ameliorate systemic inflammation and IR in obesity partially due to inhibition of inflammatory signaling in adipose tissue cells as well as bone marrow-derived immune cells.

Altered Pharmacokinetics and Hepatic Uptake of TBuMA in Ethynylestradio-Induced Cholestasis

  • Hong Soon-Sun;Choi Jong-Moon;Jin Hyo-Eon;Shim Chang-Koo
    • Archives of Pharmacal Research
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    • v.29 no.4
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    • pp.323-327
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    • 2006
  • The objective of this study was to examine the pharmacokinetics of organic cations in intrahepatic cholestatic rats. A pretreatment with $17{\alpha}$-ethynylestradiol was used to induce intrahepatic cholestasis, and tributylmethylammonium (TBuMA) was used as a representative model organic cation. When $[^3H]$TBuMA was intravenously administered, the AUC value for TBuMA was significantly increased by $79\%$ in cholestasis, and its total systemic clearance was consequently decreased by $46\%$. In addition, the in vivo hepatic uptake clearance of TBuMA from the plasma to the liver was decreased by $50\%$ in cholestasis. The concentration of bile salts in plasma was increased by 2.1 fold in cholestatic rats. Since TBuMA forms ion-pair complexes with anionic components such as bile salts, the decreased hepatic uptake of TBuMA in cholestasis may be due to a change in endogenous components, e.g., bile salts in the plasma. In isolated normal hepatocytes, the uptake clearance for TBuMA in the presence of cholestatic plasma was decreased by $20\%$ compared with normal plasma. Therefore, we conclude that the inhibition of the hepatic uptake process by the cholestasis may be in part due to the increased formation of ion-pair complexes of TBuMA with bile salts in the plasma.

Effect of a Sargassum serratifolium Extract on Neuroinflammation Induced by Lipopolysaccharides in Mice (LPS로 유도한 마우스의 급성신경염증에 대한 톱니모자반(Sargassum serratifolium) 추출물의 효과)

  • Choi, Min-Woo;Kim, Hyeung-Rak;Lee, Hyoung-Gon;Kim, Jae-Il
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.52 no.1
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    • pp.81-86
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    • 2019
  • The common hallmark of several neurodegenerative disorders, including Alzheimer's disease (AD), is the presence of chronic neuroinflammation, which contributes to the loss of neuronal structure and function. This study investigated the effects of an ethanolic extract of Sargassum serratifolium (SSE) in a lipopolysaccharides (LPS)-induced murine neuroinflammation model. Mice were administered SSE (100 mg/kg body weight) or vehicle for 5 days by oral gavage, and then treated with LPS or saline by intraperitoneal injection. Thereafter, the brain tissues were collected, and the expression of pro-inflammatory cytokines was analyzed by quantitative real-time RT-PCR. There was a marked increase in the spleen weight index in the LPS-treated groups, which indicated the induction of acute systemic inflammation. Based on significant increases in the levels of IL-1 and IL-6 expression, the induction of neuroinflammation was also evident in the cortex and hippocampus of the LPS-treated groups. The overall expression of IL-1 and IL-6 was decreased slightly by SSE administration, compared with the LPS group, and a marked change in IL-1 was observed in the cortex of the SSE-treated (SSE/LPS) group. These results suggest that SSE has potential as an anti-neuroinflammatory nutraceutical.

Metabolic Syndrome Prediction Model for Koreans in Recent 20 Years: A Systematic review (최근 10년간 한국인 대상 대사증후군 예측 모델에 대한 체계적 문헌고찰)

  • Seong, Daikyung;Jeong, Kyoungsik;Lee, Siwoo;Baek, Younghwa
    • The Journal of the Korea Contents Association
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    • v.21 no.8
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    • pp.662-674
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    • 2021
  • Metabolic syndrome is closely associated with cardiovascular disease, there is increasing attentions in prevention of metabolic syndrome through prediction. The aim of this study was to systematically review the literature by collecting, analyzing, and synthesizing articles of predicting metabolic syndrome in Koreans. For systemic review, data search was conducted on Global journals Pubmed, WoS and domestic journals DBPia, KISS published in 2011-2020 year. Three keyword 'Metabolic syndrome', 'predict', and 'korea' were used for searching under AND condition. Total 560 articles were searched and the final 22 articles were selected according to the data selection criteria. The most useful variable was WHtR(AUC=0.897), most frequently used analysis method was logistic regression(63.6%), and most accurate analysis method was XGBOOST(AUC=0.879) for predicting metabolic syndrome. Prediction accuracy was slightly improved when sasang constitution types was used. Based on the results of this study, it is believed that various large-scale longitudinal studies for the prediction and management of the Metabolic syndrome in Korean should be followed in the future.

A Study on the Blood Sugar Improvement Effect and Safety of Galgunhwangryunhwanggum-tang for Type 2 Diabetes without Complications: A Systemic Review and Meta-Analysis (합병증을 동반하지 않은 2형 당뇨병에 대한 갈근황금황련탕의 혈당개선 효과와 안전성 연구 : 체계적 문헌고찰과 메타분석)

  • Shin, Jae-ik;Baek, Ji-soo;Cho, Chung-sik
    • The Journal of Internal Korean Medicine
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    • v.43 no.1
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    • pp.22-40
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    • 2022
  • Objectives: The purpose of this study is to assess the antidiabetic effect and safety of Galgunhwangryunhwanggum-tang for type 2 diabetes without complications by analyzing related research. Methods: For a systematic review and meta-analysis, we searched for the antidiabetic effect and safety of Galgunhwangryunhwanggum-tang for type 2 diabetes without complications in 10 databases up to September 2021. Only randomized controlled trials were chosen. Results: In the treatment effectiveness analysis and meta-analysis, Galgunhwangryunhwanggum-tang had significant improvement effects on fasting plasma glucose level, 2-hour postprandial glucose level, glycated hemoglobin, fasting insulin, and homeostasis model assessment for insulin resistance compared to the control group when treated in parallel with oral glycemic drugs. Conclusion: Galgunhwangryunhwanggum-tang is effective in improving blood sugar and insulin resistance in type 2 diabetes patients without complications and can especially be considered in parallel treatment with oral hypoglycemic drugs. A large-scale randomized controlled clinical trial is required to complement the limitations presented in this study in the future.

Antiasthmatic effects on Pinellia ternate Breitenbach(PTB) water extracts against airway inflammation and hyperresponsiveness induced by diesel exhaust particles with ovalbumin sensitization in BALB/c mice (생쥐에서 ovalbumin과 디젤배기가스 입자로 유도된 기도염증과 기도 과민성에 대한 반하 물 추출물의 항천식 효과)

  • Kim, Seung Hyung;Lim, Heung Bin
    • The Korea Journal of Herbology
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    • v.28 no.1
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    • pp.65-71
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    • 2013
  • Objectives : Asthma is a chronic, complex respiratory disease, caused by airway obstruction, airway eosinophilic inflammation(AEI), and airway hyperresponsiveness(AHR). This study was conducted to determine whether oral administration of crude water extracts of Pinellia ternate Breitenbach(PTB) has an antiasthmatic potential in the treatment of asthma in mice. Methods : Asthmatic AEI and AHR were induced by systemic sensitization to ovalbumin(OVA) by intratracheal instillation with 0.1 mg/mL suspension of diesel exhaust particles(DEP) once a week for 10 weeks in BALB/c mice. Crude PTB water extracts(50 mg/kg and 200 mg/kg) were orally administered 5 times a week for 10 weeks. Cyclosporin(10 mg/kg) was administrered the same manner as a positive control. Results : Long-term treatment with crude PTB water extracts suppressed the infiltration of inflammatory cells, including eosinophils, into airways from blood. It also reduced asthmatic AEI and AHR by attenuating the increase in the levels of cytokines such as interleukin(IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid(BALF), as well as the levels of histamine and OVA-specific IgE in blood. However, the effect of crude PTB water extracts(200 mg/kg) was not likely to be stronger than that of cyclosporin(10 mg/kg). Conclusion : These results suggest that crude PTB water extracts have inhibitory effects on AEI and AHR in a mouse model of asthma and may act as a potential Th2 cytokine antagonist, and have a therapeutic effect on allergic asthma.

Clinical outcomes of direct-acting oral anticoagulants compared to warfarin in patients with non-valvular atrial fibrillation (비판막성심방세동 환자에서 직접작용 경구용 항응고제 임상적 효과와 부작용 연구)

  • Hong, Jiwon;Jung, Minji;Lee, Sukhyang
    • Korean Journal of Clinical Pharmacy
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    • v.32 no.1
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    • pp.37-46
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    • 2022
  • Background: Non-valvular atrial fibrillation (NVAF) is associated with ischemic stroke risk in the aging population. Observational studies have indicated beneficial effects of direct-acting oral anticoagulant (DOAC) against ischemic stroke compared to warfarin. This study aimed to investigate ischemic stroke incidence and bleeding risk in patients on DOAC therapy. Methods: Using the database of Korean Health Insurance Review and Assessment-Aged Patient Sample 2015, we conducted a retrospective cohort study. Study subjects with NVAF diagnosis and prescribed anticoagulants were enrolled. Propensity score (PS) matching by age, sex, comorbidities, and medications were used. The clinical outcomes were major adverse cerebro-cardiovascular events (MACCEs, ischemic stroke/systemic embolism, myocardial infarction, cardiac death) and bleeding events. A cox proportional hazard model analysis was performed to compare the outcomes with hazard ratio (HR) and 95% confidence interval (CI). Results: Total 4,773 elderly patients with NVAF were initially included. Four PS-matched groups including rivaroxaban vs. warfarin-only (n=1,079), dabigatran vs. warfarin-only (n=721), rivaroxaban vs. dabigatran (n=721), and switchers of warfarin to rivaroxaban vs. warfarin-only (n=287) were analyzed. Every group showed statistically similar results of MACCEs and bleeding events, except for the group of rivaroxaban vs. dabigatran. Rivaroxaban users showed higher risks of bleeding events than dabigatran users (HR 2.25, 95% CI 1.01-4.99). Conclusion: In the elderly patients with NVAF, efficacy and safety outcomes among oral anticoagulants including DOACs and warfarin were similar, while rivaroxaban are more likely to have higher bleeding risks than dabigatran. Further research using large size sample is needed.

Critical Adjuvant Influences on Preventive Anti-Metastasis Vaccine Using a Structural Epitope Derived from Membrane Type Protease PRSS14

  • Ki Yeon Kim;Eun Hye Cho;Minsang Yoon;Moon Gyo Kim
    • IMMUNE NETWORK
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    • v.20 no.4
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    • pp.33.1-33.19
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    • 2020
  • We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both TH1 and TH2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces TH2 and TH17 responses but reduces TH1 and Treg responses regardless of adjuvant type, whereas CFA but not alum increased follicular TH response. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.