• Title/Summary/Keyword: cumulative exposure

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Heart Failure With Preserved Ejection Fraction and Frailty: From Young to Superaged Coexisting HFpEF and Frailty

  • Amina Rakisheva;Anzhela Soloveva;Anastasia Shchendrygina;Ilya Giverts
    • International Journal of Heart Failure
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    • v.6 no.3
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    • pp.93-106
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    • 2024
  • Being commonly diagnosed in elderly women and associated with comorbidities as well as ageing-related cardio-vascular changes, heart failure with preserved ejection fraction (HFpEF) has been recently considered as a distinct cardiogeriatric syndrome. Frailty is another frequent geriatric syndrome. HFpEF and frailty share common underlying mechanisms, often co-exist, and represent each other's risk factors. A threshold of 65 years old is usually used to screen patients for both frailty and HFpEF in research and clinical settings. However, both HFpEF and frailty are very heterogenous conditions that may develop at younger ages. In this review we aim to provide a broader overview on the coexistence of HFpEF and frailty throughout the lifetime. We hypothesize that HFpEF and frailty patients' profiles (young, elderly, superaged) represent a continuum of the common ageing process modified by cumulative exposure to risk factors resulting to a presentation of HFpEF and frailty at different ages. We believe, that suggested approach might stimulate assessment of frailty in HFpEF assessment and vice versa regardless of age and early implementation of targeted interventions. Future studies of pathophysiology, clinical features, and outcomes of frailty in HFpEF by age are needed.

Dose Assessment of the Eye of the Operator in the Field of Angiography and Interventional Radiography (혈관조영 및 중재적 시술 분야 내 종사자의 눈에 대한 선량평가)

  • Kim, Jung-hoon;Cho, Yong-In
    • Journal of the Korean Society of Radiology
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    • v.12 no.2
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    • pp.209-216
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    • 2018
  • In the field of angiography and interventional radiology, it is said that the risk of radiation exposure to the eyes is high due to the characteristics of work, but currently divided dose assessment and management are not carried out in reality. Therefore, in this study, in order to evaluate the dose of the operator in the surgical environment and to analyze the shields, firstly, we selected the point where the operator is mainly located, evaluated the exposure dose of the eye after attaching the pocket dosimeter to the lateral angle point of the head and neck phantom, and evaluate shielding effect when wearing lead glasses that is currently commercialized. Secondly, we evaluated the tendency of the exposure dose of the eye and the shielding effect through simulation in the same geometric structure as the actual measurement. As a result, in the case of measurement using a dosimeter, the cumulative dose increased with the increase of the fluoroscopic time, and the tendency was different according to the position of the operator. Simulation results show that the dose distribution of the eye lens in the mathematical phantom is about 1.1 ~ 1.3 times higher than that of the cornea. Also, The protective effect of the lead glasses showed a shielding effect of at least 3.7 ~ 21.4% in each eye.

In Vitro Pharmacodynamics of CKD-602 in HT-29 Cells

  • Park, In-Sook;Ahn, Mee-Ryung;Suh, Soo-Kyung;Choi, Hong-Serck;Sohn, Soo-Jung;Yang, Ji-Sun;Yoo, Tae-Moo;Kuh, Hyo-Jeong
    • Archives of Pharmacal Research
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    • v.25 no.5
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    • pp.718-723
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    • 2002
  • CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin) is a recently-developed synthetic camptothecin analogue and currently under clinical development by Chong Kun Dang Pharm (Seoul, Korea). CKD-602 showed potent topoisomerase inhibitory activity in vitro and broad antitumor activity against various human tumor cells in vitro and in vivo in animal models. This study describes the pharmacodynamics of the immediate and delayed cytotoxicity induced by CKD-602 in a human colorectal adenocarcinoma cell line, HT-29, and its intracellular drug accumulation by HPLC. The present study was designed to address whether the higher activity of CKD-602 with prolonged exposure is due to delayed exhibition of cytotoxicity and/or an accumulation of anti proliferative effect on continuous drug exposure. The drug uptake study was performed to determine whether the delayed cytotoxicity is due to a slow drug accumulation in cells. CKD-602 produced a cytotoxicity that was exhibited immediately after treatment (immediate effect) and after treatment had been terminated (delayed effect). Both the immediate and delayed effects of CKD-602 showed a time dependent decrease in 4IC_{50}$ values. Drug uptake was biphasic and the second equilibrium level was obtained as early as at 24hr, indicating that the cumulative and delayed antitumor effects of CKD-602 were not due to slow drug uptake. On the other hand, CKD-602 treatment was sufficient to induce delayed cytotoxicity after 4hr, however, longer treatment (>24hr) enhanced its cytotoxicity due to the intracellular accumulation of the drug, which requires 24hr to reach maximum equilibrium concentration. In addition, $C^n$$\times$T=h analysis (n=0.481) indicated that increased exposure times may contribute more to the overall antitumor activity of CKD-602 than drug concentration. Additional studies to determine the details of the intracellular uptake kinetics (e.g., concentration dependency and retention studies) are needed in order to identify the optimal treatment schedules for the successful clinical development of CKD-602.

An Analytic Study on the Effect of Carbon Disulfide on the Blood Pressure (이황화탄소 폭로가 혈압에 미치는 영향에 관한 분석적 연구)

  • Park, Jong-Tae;Kim, Hae-Joon;Yum, Yong-Tae;Paek, Do-Myung
    • Journal of Preventive Medicine and Public Health
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    • v.27 no.3 s.47
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    • pp.581-595
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    • 1994
  • To investigate the effect of carbon disulfide on blood pressure, the BP measurements in the periodic health examination results and the medical records of factory clinic were reviewed. The study subjects were composed of 1336 male and 544 female workers, who were categorized into three groups by the exposure status-highly exposed, moderately exposed and non-exposed group. The results of the study were as follows; 1. The age-adjusted mean systolic and diastolic BP of male workers were 122.35 mmHg/79.11 mmHg in highly exposed, 121.57mmHg/79.05mmHg in moderately exposed and 122.67mmHg/82.27mmHg in non-exposed group. For female workers, BPs were 115.13mmHg/74.49mmHg in moderately exposed and 113.48mmHg/74.30mmHg in non-exposed group. 2. In multiple regression analysis of maximum BP against Age and tenure, the slope coefficients of age and tenure on the systolic BP were 0.379, 0.667 respectively and those on the diastolic BP were 0.331, 0.405 respectively in highly exposed male workers. Tenure was a significant variable in this study. For female workers, however the slope coefficients of tenure on BP were significant only for systolic BP of moderately-exposed group. 3. In multiple regression analysis of Bp against age, cumulative exposure index (CEI), cholesterol, all the variables showed significant slope coefficients in male, but age and CEI on systolic BP were significant for female workers (p<0.05). 4. In the multiple analysis of the amount of Bp change and the velocity of Bp change among male workers, the slope coefficients of tenure tended to increase as exposure level increased. Among female workers, the slope coefficients of tenure were significant on the amount of Bp change and the velocity of Bp change in moderately exposed group.

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Selection of Representative Foods and 'Best-fit' Mapping of Other Foods for Estimation of a Comprehensive Exposure to Food Contaminants in a Korean Total Diet Study (한국인의 유해물질 식이 노출량 평가를 위한 대표식품 선정과 mapping)

  • Koh, Eun-Mi;Shin, Hye-Hyung;Yon, Mi-Yong;Nam, Eun-Jeong;Lee, Yoon-Na;Kim, Do-Hee;Lee, Jee-Yeon;Kim, Mee-Hye;Park, Sung-Kug;Choi, Hoon;Kim, Cho-Il
    • Korean Journal of Food Science and Technology
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    • v.43 no.6
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    • pp.773-782
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    • 2011
  • A food list representing the typical diet of Koreans was developed for a total diet study based on the 687 food items which appeared in the dietary intake data collected during the 2008 & 2009 Korea National Health & Nutrition Examination Survey. Food items included in 90% of the cumulative intake, items with a consumption frequency of 5% or higher and items contributing to 80% of cumulative fat intake were considered first. From the resulting 165 food items, 15 items were removed to avoid similar foods, while 10 distinct items were added to increase the efficiency of 'best-fit' mapping. Consequently, 160 items were selected as representative foods, which cover 90.93% of intake amount, 91.36% of energy intake and 89.05% of fat intake. Given that every food consumed by Koreans can't be analyzed for contaminants of interest, mapping other foods to the previously mentioned representative 160 foods is warranted because it enables a more comprehensive dietary exposure assessment that is close to reality.

Determination of Target Clean-up Level and Risk-Based Remediation Strategy (위해성에 근거한 정화목표 산정 및 복원전략 수립)

  • Ryu, Hye-Rim;Han, Joon-Kyoung;Nam, Kyoung-Phile
    • Journal of Soil and Groundwater Environment
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    • v.12 no.1
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    • pp.73-86
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    • 2007
  • Risk-based remediation strategy (RBRS) is a consistent decision-making process for the assessment and response to chemical release based on protecting human health and the environment. The decision-making process described integrates exposure and risk assessment practices with site assessment activities and remedial action selection to ensure that the chosen actions are protective of human health and the environment. The general sequences of events in Tier 1 is as follows: initial site assessment, development of conceptual site model with all exposure pathways, data collection on pollutants and receptors, and identification of risk-based screening level (RBSL). If site conditions do not meet RBSL, it needs further site-specific tier evaluation, Tier 2. In most cases, only limited number of exposure pathways, exposure scenarios, and chemicals of concern are considered the Tier 2 evaluation since many are eliminated from consideration during the Tier 1 evaluation. In spite of uncertainties due to the conservatism applied to risk calculations, limitation in site-specific data collections, and variables affecting the selection of target risk levels and exposure factors, RBRS provides us time- and cost-effectiveness of the remedial action. To ensure reliance of the results, the development team should consider land and resource use, cumulative risks, and additive effects. In addition, it is necessary to develop appropriate site assessment guideline and reliable toxicity assessment method, and to study on site-specific parameters and exposure parameters in Korea.

Chromosome Aberrations and Sister Chromatid Exchanges of Hospital Workers Exposed to Radiation (방사선취급 병원근무자들의 염색체이상 및 자매염색분체교환 빈도)

  • Cha, Ae-Ri;Kim, Mi-Sun;Hwang, In-Kyung;Lee, Su-Ill;Cho, Byung-Mann;Kim, Don-Kyoun
    • Journal of Preventive Medicine and Public Health
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    • v.31 no.4 s.63
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    • pp.616-627
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    • 1998
  • In order to evaluate the cytogenetic hazard among hospital workers potentially exposed to low dose of radiation, the analysis of chromosome aberrations(CA) and sister chromatid exchanges(SCE) in lymphocytes were performed in 79 hospital workers and 79 non-exposed workers. The mean frequency of chromosomal exchange and deletion(respectively, $0.20\times10^{-2}/cell\;and\;0.39\times10^{-2}/cell$) in the exposed group were significantly higher than those$(0.07\times10^{-2}/cell\;and\;0.23\times10^{-2}/cell)$ in control group. The frequency of sister chromatid exchanges was 5.04/cell in the control vs. 6.57/cell in the exposed group. There were also significant differences in the mean frequencies of CA and SCE adjusted for age, sex, smoking, drinking between two groups. There were no evidence of significant increase of CA and SCE according to the department or duration of employment. But the frequency of cells having chromosome aberration was significantly higher in the exposed group than in the control group related to duration of employment. There was no dose-effect relationship between the cumulative doses and the frequency of CA and SCE. But in the case of last 1 yr cumulative dose, there were evidence of significant dose-dependant increase of chromosome type CA and percentage of cells with aberration. The result suggest that there is cytogenetic hazard in risk group like hospital workers handling low dose radiation. And the analysis CA and SCE are useful biological indicators for the exposure of low dose level of radiation.

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The Characteristics and Survival Rates of Evergreen Broad-Leaved Tree Plantations in Korea (난대상록활엽수종 조림지 활착률과 영향인자)

  • Park, Joon-Hyung;Jung, Su-Young;Lee, Kwang-Soo;Lee, Ho-Sang
    • Journal of Korean Society of Forest Science
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    • v.108 no.4
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    • pp.513-521
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    • 2019
  • With rapid climate change and increasing global warming, the distribution of evergreen broad-leaved trees (EBLTs) is gradually expanding to the inland regions of Korea. The aim of the present study was to analyze the survival rate of 148 EBLT plantations measuring 180 ha and to determine the optimal plantation size that would help in coping with climate change in the warm, temperate climate zone of the Korean peninsula. For enhancing the reliability of our estimated survival model, we selected a set of 11 control variables that may have also influenced the survival rates of the EBLTs in the 148 plantations. The results of partial correlation analysis showed that the survival rate of 67.0±26.9 of the EBLTs in the initial plantation year was primarily correlated with plantation type by the crown closure of the upper story of the forest, wind exposure, and precipitation. For predicting the probability of survival by quantification theory, 148 plots were surveyed and analyzed with 11 environmental site factors. Survival rate was in the order of plantation type by the crown closure of upper story of the forest, wind exposure, total cumulative precipitation for two weeks prior to planting, and slope stiffness in the descending order of score range in the estimated survival model for the EBLTs with the fact that survival rate increased with shade rate of upper story to some extent.

Inhalation of Bacterial Cellulose Nanofibrils Triggers an Inflammatory Response and Changes Lung Tissue Morphology of Mice

  • Silva-Carvalho, Ricardo;Silva, Joao P.;Ferreirinha, Pedro;Leitao, Alexandre F.;Andrade, Fabia K.;da Costa, Rui M. Gil;Cristelo, Cecilia;Rosa, Morsyleide F.;Vilanova, Manuel;Gama, F. Miguel
    • Toxicological Research
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    • v.35 no.1
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    • pp.45-63
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    • 2019
  • In view of the growing industrial use of Bacterial cellulose (BC), and taking into account that it might become airborne and be inhaled after industrial processing, assessing its potential pulmonary toxic effects assumes high relevance. In this work, the murine model was used to assess the effects of exposure to respirable BC nanofibrils (nBC), obtained by disintegration of BC produced by Komagataeibacter hansenii. Murine bone marrow-derived macrophages ($BMM{\Phi}$) were treated with different doses of nBC (0.02 and 0.2 mg/mL, respectively 1 and $10{\mu}g$ of fibrils) in absence or presence of 0.2% Carboxymethyl Cellulose (nBCMC). Furthermore, mice were instilled intratracheally with nBC or nBCMC at different concentrations and at different time-points and analyzed up to 6 months after treatments. Microcrystaline $Avicel-plus^{(R)}$ CM 2159, a plant-derived cellulose, was used for comparison. Markers of cellular damage (lactate dehydrogenase release and total protein) and oxidative stress (hydrogen peroxidase, reduced glutathione, lipid peroxidation and glutathione peroxidase activity) as well presence of inflammatory cells were evaluated in brochoalveolar lavage (BAL) fluids. Histological analysis of lungs, heart and liver tissues was also performed. BAL analysis showed that exposure to nBCMC or CMC did not induce major alterations in the assessed markers of cell damage, oxidative stress or inflammatory cell numbers in BAL fluid over time, even following cumulative treatments. $Avicel-plus^{(R)}$ CM 2159 significantly increased LDH release, detected 3 months after 4 weekly administrations. However, histological results revealed a chronic inflammatory response and tissue alterations, being hypertrophy of pulmonary arteries (observed 3 months after nBCMC treatment) of particular concern. These histological alterations remained after 6 months in animals treated with nBC, possibly due to foreign body reaction and the organism's inability to remove the fibers. Overall, despite being a safe and biocompatible biomaterial, BC-derived nanofibrils inhalation may lead to lung pathology and pose significant health risks.

FARFARAE FLOS INHIBITS HISTAMINE-INDUCED CONTRACTILE RESPONSES OF AIRWAY SMOOTH MUSCLE (관동화전탕액(款冬花煎湯液)이 기관지평골근(氣管支平滑筋)에 미치는 영향(影響))

  • Han, Jong-Hyun;Kang, Sung-Yong;Yu, Kwang-Suk;Jin, Sang-Sik;Ha, Kyung-Hwa;Lee, Kyung-Ja
    • The Journal of Internal Korean Medicine
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    • v.17 no.1
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    • pp.210-217
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    • 1996
  • Farfarae Flos, a traditional herb medicine, has been used in Korea and China for many centuries as a treatment for respiratory disease. The purpose of the present study was to determine the effect of Farfarae Flos on histamine-induced tracheal smooth muscle contraction in rats. Guinea pigs(500g, female) were killed by CO2 exposure and a segment (8-10mm) of the thoracic trachea from each guinea pig was cut into equal segments and mounted 'in pairs' in a tissue bath. Contractile force was measured with force displacement transducers under 0.5g loading tension. The dose of histamine which evoked 50% of maximal response (ED50) was obtained from cumulative dose response curves for histamine (10-7-10-4M). Contractions evoked by histamine(ED50) were inhibited significantly by Farfarae Flos. The mean percent inhibition was 8.7% after 1.5mg/ml Farfarae Flos, and 33.5% (p<0.05) after 5.0mg/ml Farfarae Flos. Propranolol (10-7M) slightly but significantly attenuated the inhibitory effects of Farfarae Flos. Following treatment with propranolol, the mean percent inhibition caused by 5.0mg/ml Farfarae Flos. Indomethacin and methylene blue (10-7M) did not significantly alter the inhibitory effect of Farfarae Flos. These results indicate that Farfarae Flos can relax histamine-induced contraction of guinea pig tracheal smooth muscle, and that this inhibition involves, in part, symphathetic nerve system.

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