15 research outputs found

    Effect of changes in inspired oxygen fraction on oxygen delivery during cardiac surgery: a substudy of the CARROT trial

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    When hemoglobin (Hb) is fully saturated with oxygen, the additional gain in oxygen delivery (DO2) achieved by increasing the fraction of inspired oxygen (FiO2) is often considered clinically insignificant. In this study, we evaluated the change in DO2, interrogated by mixed venous oxygen saturation (SvO2), in response to a change in FiO2 of 0.5 during cardiac surgery. When patients were hemodynamically stable, FiO2 was alternated between 0.5 and 1.0 in on-pump cardiac surgery patients (pilot study), and between 0.3 and 0.8 in off-pump coronary artery bypass grafting patients (substudy of the CARROT trial). After the patient had stabilized, a blood gas analysis was performed to measure SvO2. The observed change in SvO2 (ฮ”SvO2) was compared to the expected ฮ”SvO2 calculated using Fick's equation. A total 106 changes in FiO2 (two changes per patient; total 53 patients; on-pump, n = 36; off-pump, n = 17) were finally analyzed. While Hb saturation remained near 100% (on-pump, 100%; off-pump, mean [SD] = 98.1% [1.5] when FiO2 was 0.3 and 99.9% [0.2] when FiO2 was 0.8), SvO2 changed significantly as FiO2 was changed (the first and second changes in on-pump, 7.7%p [3.8] and 7.6%p [3.5], respectively; off-pump, 7.9%p [4.9] and 6.2%p [3.9]; all P < 0.001). As a total, regardless of the surgery type, the observed ฮ”SvO2 after the FiO2 change of 0.5 was โ‰ฅ 5%p in 82 (77.4%) changes and โ‰ฅ 10%p in 31 (29.2%) changes (mean [SD], 7.5%p [3.9]). Hb concentration was not correlated with the observed ฮ”SvO2 (the first changes, r = - 0.06, P = 0.677; the second changes, r = - 0.21, P = 0.138). The mean (SD) residual ฮ”SvO2 (observed - expected ฮ”SvO2) was 0%p (4). Residual ฮ”SvO2 was more than 5%p in 14 (13.2%) changes and exceeded 10%p in 2 (1.9%) changes. Residual ฮ”SvO2 was greater in patients with chronic kidney disease than in those without (median [IQR], 5%p [0 to 7] vs. 0%p [- 3 to 2]; P = 0.049). DO2, interrogated by SvO2, may increase to a clinically significant degree as FiO2 is increased during cardiac surgery, and the increase of SvO2 is not related to Hb concentration. SvO2 increases more than expected in patients with chronic kidney disease. Increasing FiO2 can be used to increase DO2 during cardiac surgery.ope

    The Effect of Electrical Muscle Stimulation and In-bed Cycling on Muscle Strength and Mass of Mechanically Ventilated Patients: A Pilot Study

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    Background: Critically ill patients experience muscle weakness, which leads to functional disability. Both functional electrical stimulation (FES) and in-bed cycling can be an alternative measure for intensive care unit (ICU) patients who are not feasible for active exercise. The aim of this study was to examine whether FES and in-bed cycling have a positive effect on muscle mass in ICU patients. Methods: Critically ill patients who received mechanical ventilation for at least 24 hours were included. After passive range of motion exercise, in-bed cycling was applied for 20 minutes, and FES was applied for 20 minutes on the left leg. The right leg received in-bed cycling and the left leg received both FES and in-bed cycling. Thigh circumferences and rectus femoris cross-sectional area (CSA) were assessed with ultrasonography before and after the intervention. Muscle strength was assessed by Medical Research Council scale. Results: A total of 10 patients were enrolled in this study as a pilot study. Before and after the intervention, the CSA of right rectus femoris increased from 5.08 ยฑ 1.51 cm2 to 6.01 ยฑ 2.21 cm2 , which was statistically significant (P = 0.003). The thigh circumference was also increased and statistically significant (P = 0.006). There was no difference between left and right in regard to FES application. There is no significant change in muscle strength before and after the intervention (right and left, P = 0.317 and P = 0.368, respectively). Conclusions: In-bed cycling increased thigh circumferences rectus femoris CSA. Adding FES did not show differences.ope

    Combination of Static Echocardiographic Indices for the Prediction of Fluid Responsiveness in Patients Undergoing Coronary Surgery: A Pilot Study

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    We investigated the role of echocardiographic indices consisting of left ventricular end-diastolic area (LVEDA) in combination with Doppler-derived surrogates of diastolic compliance and filling (E/E', E'/S', E'/A'; early transmitral flow velocity (E), tissue Doppler-derived early (E') diastolic, late (A') diastolic, or peak systolic (S') velocity of the mitral annulus) in predicting fluid responsiveness in off-pump coronary surgery. Hemodynamic and echocardiographic variables were prospectively assessed under general anesthesia before and after a fluid challenge of 6 mL/kg during apnea at atmospheric pressure in 64 patients with LV ejection fraction โ‰ฅ40%. Forty patients (63%) were fluid responders (โ‰ฅ15% increase in stroke volume index). E/E' and E'/S' could predict fluid responsiveness with area under the receiver operating characteristic curve (AUROC) of 0.71 (95% confidence interval [CI], 0.56-0.85; p = 0.006) and 0.68 (95% CI, 0.54-0.82; p = 0.017), respectively. The combination of LVEDA and E/E' showed incremental predictive ability for fluid responsiveness compared with LVEDA (AUROC, 0.60; p = 0.170) or pulse pressure variation (AUROC, 0.70; p = 0.002), yielding the highest AUROC of 0.78 (95% CI, 0.66-0.90; p < 0.001). The combined index of echocardiographic variables reflecting LV dimension (LVEDA) and diastolic compliance and filling (E/E') is a potentially useful predictor of fluid responsiveness.ope

    Associations of creatinine/cystatin C ratio and postoperative pulmonary complications in elderly patients undergoing off-pump coronary artery bypass surgery: a retrospective study

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    Sarcopenia along with nutritional status are associated with postoperative pulmonary complications in various surgical fields. Recently, the creatinine/cystatin C ratio and CONtrolling NUTritional status score were introduced as biochemical indicators for sarcopenia and malnutrition, respectively. We aimed to investigate the associations among these indicators and postoperative pulmonary complications in elderly patients undergoing off-pump coronary artery bypass surgery. We reviewed the medical records of 605 elderly patients (aged โ‰ฅ 65 years) who underwent off-pump coronary artery bypass surgery from January 2010 to December 2019. Postoperative pulmonary complications (pneumonia, prolonged ventilation [> 24 h], and reintubation during post-surgical hospitalisation) occurred in 80 patients. A 10-unit increase of creatinine/cystatin C ratio was associated with a reduced risk of postoperative pulmonary complications (odds ratio: 0.80, 95% confidence interval: 0.69-0.92, P = 0.001); the optimal cut-off values for predicting postoperative pulmonary complications was 89.5. Multivariable logistic regression analysis revealed that age, congestive heart failure, and creatinine/cystatin C ratio < 89.5 (odds ratio 2.36, 95% confidence interval 1.28-4.37) were independently associated with the occurrence of postoperative pulmonary complications, whereas CONtrolling NUTritional status score was not. A low creatinine/cystatin C ratio was associated with an increased risk of developing postoperative pulmonary complications after off-pump coronary artery bypass surgery.ope

    Inhalation sedation for postoperative patients in the intensive care unit: initial sevoflurane concentration and comparison of opioid use with propofol sedation

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    Background: Although the use of volatile sedatives in the intensive care unit (ICU) is increasing in Europe, it remains infrequent in Asia. Therefore, there are no clinical guidelines available. This study investigates the proper initial concentration of sevoflurane, a volatile sedative that induces a Richmond agitation-sedation scale (RASS) score of -2 to -3, in patients who underwent head and neck surgery with tracheostomy. We also compared the amount of postoperative opioid consumption between volatile and intravenous (IV) sedation. Methods: We planned a prospective study to determine the proper initial sevoflurane concentration and a retrospective analysis to compare postoperative opioid consumption between volatile sedation and propofol sedation. Patients scheduled for head and neck surgery with tracheostomy and subsequent postoperative sedation in the ICU were enrolled. Results: In this prospective study, the effective dose 50 (ED50) of initial end-tidal sevoflurane concentration was 0.36% (95% confidence interval [CI], 0.20 to 0.60%), while the ED 95 was 0.69% (95% CI, 0.60 to 0.75%) based on isotonic regression methods. In this retrospective study, remifentanil consumption during postoperative sedation was significantly lower in the sevoflurane group (2.52ยฑ1.00 ยตg/kg/hr, P=0.001) than it was in the IV propofol group (3.66ยฑ1.30 ยตg/kg/hr). Conclusions: We determined the proper initial end-tidal concentration setting of sevoflurane for patients with tracheostomy who underwent head and neck surgery. Postoperative sedation with sevoflurane appears to be a valid and safe alternative to IV sedation with propofol.ope

    High Preoperative Serum Syndecan-1, a Marker of Endothelial Glycocalyx Degradation, and Severe Acute Kidney Injury after Valvular Heart Surgery

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    Degradation of endothelial glycocalyx (EG) is associated with inflammation and endothelial dysfunction, which may contribute to the development of acute kidney injury (AKI). We investigated the association between a marker of EG degradation and AKI after valvular heart surgery. Serum syndecan-1 concentrations were measured at induction of anesthesia and discontinuation of cardiopulmonary bypass in 250 patients. Severe AKI was defined as Kidney Disease: Improving Global Outcomes Criteria Stage 2 or 3. Severe AKI occurred in 13 patients (5%). Receiver operating characteristic analysis of preoperative syndecan-1 to predict severe AKI showed area under curve of 0.714 (95% confidence interval (CI), 0.575-0.853; p = 0.009). The optimal cut-off value was 90 ng/mL, with a sensitivity of 61.5% and specificity of 78.5%. In multivariable analysis, both preoperative syndecan-1 โ‰ฅ 90 ng/mL and Cleveland Clinic Foundation score independently predicted severe AKI. Severe tricuspid regurgitation was more frequent (42.4% vs. 17.8%, p < 0.001), and baseline right ventricular systolic pressure (41 (33-51) mmHg vs. 33 (27-43) mmHg, p = 0.001) and TNF-ฮฑ (1.85 (1.37-2.43) pg/mL vs. 1.45 (1.14-1.92) pg/mL, p <0.001) were higher in patients with high preoperative syndecan-1. Patients with high preoperative syndecan-1 had longer hospital stay (16 (12-24) days vs. 13 (11-17) days, p = 0.001). In conclusion, a high preoperative syndecan-1 concentration greater than 90 ng/mL was able to predict severe AKI after valvular heart surgery and was associated with prolonged hospitalization.ope

    Risk factors for intensive care unit readmission after lung transplantation: a retrospective cohort study

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    Background: Lung transplantation (LT) is an accepted therapeutic modality for end-stage lung disease patients. Intensive care unit (ICU) readmission is a risk factor for mortality after LT, for which consistent risk factors have not been elucidated. Thus, we investigated the risk factors for ICU readmission during index hospitalization after LT, particularly regarding the posttransplant condition of LT patients. Methods: In this retrospective study, we investigated all adult patients undergoing LT between October 2012 and August 2017 at our institution. We collected perioperative data from electronic medical records such as demographics, comorbidities, laboratory findings, ICU readmission, and in-hospital mortality. Results: We analyzed data for 130 patients. Thirty-two patients (24.6%) were readmitted to the ICU 47 times during index hospitalization. At the initial ICU discharge, the Sequential Organ Failure Assessment (SOFA) score (odds ratio [OR], 1.464; 95% confidence interval [CI], 1.083-1.978; P=0.013) and pH (OR, 0.884; 95% CI, 0.813-0.962; P=0.004; when the pH value increases by 0.01) were related to ICU readmission using multivariable regression analysis and were still significant after adjusting for confounding factors. Thirteen patients (10%) died during the hospitalization period, and the number of ICU readmissions was a significant risk factor for in-hospital mortality. The most common causes of ICU readmission and in-hospital mortality were infection-related. Conclusions: The SOFA score and pH were associated with increased risk of ICU readmission. Early postoperative management of these factors and thorough posttransplantation infection control can reduce ICU readmission and improve the prognosis of LT patients.ope

    Equal Ratio Ventilation Reduces Blood Loss During Posterior Lumbar Interbody Fusion Surgery

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    Study design: A prospective randomized double-blinded study. Objective: The aim of this study was to compare the effect of two different ventilator modes (inspiratory to expiratory ratio [I:E ratio] of 1:1 and 1:2) on intraoperative surgical bleeding in patients undergoing posterior lumbar interbody fusion (PLIF) surgery. Summary of background data: During PLIF surgery, a considerable amount of blood loss is anticipated. In the prone position, engorgement of the vertebral vein increases surgical bleeding. We hypothesized that equal ratio ventilation (ERV) with I:E ratio of 1:1 would lower peak inspiratory pressure (PIP) in the prone position and consequentially decrease surgical bleeding. Methods: Twenty-eight patients were randomly assigned to receive either ERV (ERV group, n = 14) or conventional ventilation with I:E ratio of 1:2 (control group, n = 14). Hemodynamic and respiratory parameters were measured at 5 minutes after anesthesia induction, at 5 minutes after the prone position, at the time of skin closure, and at 5 minutes after turning to the supine position. Results: The amount of intraoperative surgical bleeding in the ERV group was significantly less than that in the control group (975.7 ยฑ 349.9 mL vs. 1757.1 ยฑ 1172.7 mL, P = 0.030). Among other hemodynamic and respiratory parameters, PIP and plateau inspiratory pressure (Pplat) were significantly lower and dynamic lung compliance (Cdyn) was significantly higher in the ERV group than those of the control group throughout the study period, respectively (all P < 0.05). Conclusion: Compared to conventional ratio ventilation, ERV provided lower PIP and reduced intraoperative surgical blood loss in patients undergoing PLIF surgery.Level of Evidence: 2.ope

    ๋งŒ์„ฑ ์—ผ์ฆ์„ฑ ๋นˆํ˜ˆ์—์„œ hepcidin ๋ณ€ํ™”์— ๊ด€ํ•œ ์—ฐ๊ตฌ: ์ฒ ๋ถ„์ œ ํˆฌ์•ฝ ํ›„ hepcidin ์กฐ์ ˆ ๊ธฐ์ „

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    ๋งŒ์„ฑ ์—ผ์ฆ์„ฑ ๋นˆํ˜ˆ(anemia of chronic inflammation, ACI)์€ ํ™˜์ž์˜ ๋ถ€์ •์  ์˜ˆํ›„์™€ ์—ฐ๊ด€๋œ ๊ฒƒ์œผ๋กœ ์•Œ๋ ค์ ธ ์žˆ๋‹ค. Hepcidin์€ ์ฒด๋‚ด์˜ ์ฒ  ํ•ญ์ƒ์„ฑ์„ ์กฐ์ ˆํ•˜๋Š” ์ฃผ์š” ์กฐ์ ˆ ์ธ์ž๋กœ, ์ฃผ๋กœ ๊ฐ„์—์„œ ์ƒ์„ฑ๋œ๋‹ค. ๋งŒ์„ฑ ์—ผ์ฆ ์ƒํƒœ์—์„œ๋Š” hepcidin์ด ์ฆ๊ฐ€ํ•˜์—ฌ ์ฒด๋‚ด์˜ ์ฒ ์ด ํ™œ์šฉ ๋ถˆ๊ฐ€๋Šฅํ•œ ferritin์˜ ํ˜•ํƒœ๋กœ ์„ธํฌ ๋‚ด์— ์ €์žฅ๋˜๋Š”๋ฐ, ์ด๋กœ ์ธํ•ด ์ฒด๋‚ด์— ์ถฉ๋ถ„ํ•œ ์ฒ  ์ €์žฅ๋Ÿ‰์ด ์žˆ์Œ์—๋„ ๋ถˆ๊ตฌํ•˜๊ณ  ์ฒ ์˜ ์ด์šฉ์— ์ œํ•œ์ด ๋ฐœ์ƒํ•˜์—ฌ ์ ํ˜ˆ๊ตฌ ์ƒ์„ฑ์ด ์–ด๋ ค์›Œ์ง€๊ณ , ๋นˆํ˜ˆ์ด ๋ฐœ์ƒํ•˜๊ฒŒ ๋œ๋‹ค. ์ž„์ƒ์—์„œ๋Š” ๋ชจ๋“  ์ข…๋ฅ˜์˜ ๋นˆํ˜ˆ์„ ์ฒ ๋ถ„ ๋ณด์ถฉ์œผ๋กœ ์น˜๋ฃŒํ•˜๊ณค ํ•˜๋Š”๋ฐ, ACI์˜ ๊ทผ๋ณธ์ ์ธ ์›์ธ์„ ๊ณ ๋ คํ•˜์˜€์„ ๋•Œ ์ด๊ฒƒ์€ ์ ์ ˆํ•˜์ง€ ๋ชปํ•œ ์น˜๋ฃŒ๋ฒ•์ผ ๊ฐ€๋Šฅ์„ฑ์ด ์žˆ๋‹ค. ๋”ฐ๋ผ์„œ, ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” ์ž„์ƒ๊ณผ ์œ ์‚ฌํ•œ ACI ์ฅ ๋ชจ๋ธ์„ ํ™•๋ฆฝํ•˜๊ณ , ์ •๋งฅ ๋‚ด ์ฒ ๋ถ„์„ ํˆฌ์—ฌํ•œ ํ›„ ๋‹จ๊ธฐ๊ฐ„์— ๊ฑธ์ณ ๊ฐ„์—์„œ hepcidin ๋ฐ ๊ทธ ์กฐ์ ˆ ๊ฒฝ๋กœ์˜ ๋ณ€ํ™”๋ฅผ ์•Œ์•„๋ณด๋Š” ๊ฒƒ์„ ์ฃผ์š” ์—ฐ๊ตฌ ๋ชฉํ‘œ๋กœ ํ•˜์˜€๋‹ค. ๋˜ํ•œ ์ฒ ๋ถ„ ํˆฌ์—ฌ๋กœ ์ธํ•ด ๋ฐœ์ƒ ๊ฐ€๋Šฅํ•œ ์‚ฐํ™” ์ŠคํŠธ๋ ˆ์Šค๋ฅผ ํ‰๊ฐ€ํ•˜๊ณ , ์‹ ์žฅ์—์„œ์˜ erythropoietin (EPO) ๋ฐœํ˜„ ๋ฐ erythroferrone (ERFE) ๋ณ€ํ™”๋ฅผ ํ•จ๊ป˜ ์‚ดํŽด๋ณด๊ณ ์ž ํ•˜์˜€๋‹ค. ๋™์‹œ์—, knockdown HepG2 ์„ธํฌ์— ์ฒ ์„ ์ฒ˜๋ฆฌํ•˜๋Š” ์‹คํ—˜์„ ํ†ตํ•ด hepcidin ์กฐ์ ˆ ๊ฒฝ๋กœ๋ฅผ ํ™•์ธํ•˜๊ณ ์ž ํ•˜์˜€๋‹ค. ACI๋Š” Complete Freundโ€™s Adjuvant (CFA)๋ฅผ 2์ฃผ๊ฐ„ 3ํšŒ ๋ณต๊ฐ• ๋‚ด ํˆฌ์—ฌํ•˜์—ฌ ์œ ๋ฐœํ•˜์˜€๋‹ค. ์ˆ˜์ปท Sprague-Dawley ์ฅ (n = 30)๋Š” ๋‹ค์Œ์˜ 3๊ฐœ ๊ทธ๋ฃน์œผ๋กœ ๋‚˜๋ˆ„์–ด ๋ฐฐ์ •๋˜์—ˆ๋‹ค: ๋Œ€์กฐ-์‹์—ผ์ˆ˜๊ตฐ (n = 10), CFA-์‹์—ผ์ˆ˜๊ตฐ (n = 10), CFA-์ฒ ๋ถ„๊ตฐ (n = 10). CFA ํˆฌ์•ฝ ์‹œ์ž‘ 2์ฃผ ๋’ค, ํ˜ˆ์ƒ‰์†Œ ์ˆ˜์น˜๊ฐ€ ๊ธฐ์ €์น˜์— ๋น„ํ•ด >2 g/dL ๊ฐ์†Œํ•œ ๊ฒฝ์šฐ ACI๊ฐ€ ์œ ๋ฐœ๋œ ๊ฒƒ์œผ๋กœ ๋ณด์•˜๋‹ค. ACI ์ฅ๋Š” ์ •๋งฅ์œผ๋กœ ์ฒ ๋ถ„ (iron isomaltoside, 20mg/kg) ๋˜๋Š” ๋™๋Ÿ‰์˜ ์‹์—ผ์ˆ˜๋ฅผ ํˆฌ์—ฌ ๋ฐ›์•˜๋‹ค. ํˆฌ์•ฝ 3์ผ ํ›„, ํ˜ˆ์•กํ•™์  ๋ณ€์ˆ˜, ์—ผ์ฆ ํ‘œ์ง€์ž, iron profile๊ณผ ํ•จ๊ป˜ ๊ฐ„์—์„œ์˜ hepcidin ๋ฐ ๊ทธ ์ „์‚ฌ ์กฐ์ ˆ ๊ฒฝ๋กœ๋ฅผ ํ™•์ธํ•˜์˜€๋‹ค. ACI ์ฅ์—์„œ๋Š” ๋นˆํ˜ˆ๊ณผ ํ•จ๊ป˜ ์—ผ์ฆ ํ‘œ์ง€์ž์™€ ํ™œ์„ฑ ์‚ฐ์†Œ์˜ ์ฆ๊ฐ€๊ฐ€ ํ™•์ธ๋˜์—ˆ๋‹ค. ์ •๋งฅ ์ฒ ๋ถ„ ํˆฌ์—ฌ 3์ผ ๋’ค, ํ˜ˆ์ƒ‰์†Œ ์ˆ˜์น˜์—๋Š” ๋ณ€ํ™”๊ฐ€ ์—†์—ˆ์œผ๋‚˜, ๊ฐ„ ๋ฐ ํ˜ˆ์ฒญ์—์„œ hepcidin ๋†๋„๊ฐ€ ์ฆ๊ฐ€ํ•˜์˜€๊ณ , ๊ฐ„์—์„œ์˜ ferritin ์ฆ๊ฐ€๋„ ํ™•์ธ๋˜์—ˆ๋‹ค. ์ฒ ๋ถ„ ํˆฌ์•ฝ์€ ๊ฐ„์—์„œ ROS-generating NADPH oxidase-2 (NOX-2), NOX-4 ๋ฐ superoxide dismutase (SOD)์˜ ์ฆ๊ฐ€๋ฅผ ์œ ๋ฐœํ•˜์˜€๋‹ค. ACI ์ฅ์˜ ๊ฐ„์—์„œ interleukin-6/signal transducer and activator of transcription-3 (IL-6/STAT-3) ๊ฒฝ๋กœ์™€ bone morphogenetic protein/Sma mothers against decapentaplegic (BMP/SMAD) ๊ฒฝ๋กœ ํ™œ์„ฑํ™”๊ฐ€ ํ™•์ธ๋˜์—ˆ์œผ๋ฉฐ, ์ •๋งฅ ์ฒ ๋ถ„ ํˆฌ์—ฌ๋Š” IL-6์˜ ์ฆ๊ฐ€ ์—†์ด ACI ์กฐ๊ฑด ํ•˜์—์„œ ํ™œ์„ฑํ™” ๋˜์–ด ์žˆ๋˜ SMAD1/5์™€ STAT-3๋ฅผ ๋” ํ™œ์„ฑํ™”์‹œ์ผฐ๋‹ค. ์ฒ ์„ ์ฒ˜๋ฆฌํ–ˆ์„ ๋•Œ HepG2 ์„ธํฌ์—์„œ๋„ SMAD1/5์™€ STAT-3๊ฐ€ ๋ชจ๋‘ ํ™œ์„ฑํ™” ๋˜์—ˆ์œผ๋ฉฐ, ์†Œ๊ฐ„์„ญ RNAs (short interfering RNAs, siRNAs)๋ฅผ ์ด์šฉํ•œ STAT-3์™€ SMAD1/5์˜ knockdown์„ ์‹œํ–‰ํ–ˆ์„ ๋•Œ ์ฒ  ์ฒ˜๋ฆฌ๋กœ ์ธํ•œ hepcidin ์ „์‚ฌ ์ฆ๊ฐ€ ์ •๋„๊ฐ€ ์–ต์ œ๋จ์„ ํ™•์ธํ•˜์˜€๋‹ค. ์ •๋งฅ ์ฒ ๋ถ„ ํˆฌ์—ฌ๋Š” ์‹ ์žฅ์—์„œ EPO mRNA ๋ฐœํ˜„๋Ÿ‰์„ ๊ฐ์†Œ์‹œ์ผฐ์œผ๋ฉฐ, ์ด๋Š” ํ˜ˆ์ฒญ์—์„œ์˜ ERFE ๋†๋„ ๊ฐ์†Œ์™€ ๋™๋ฐ˜๋˜์—ˆ๋‹ค. ๊ฒฐ๋ก ์ ์œผ๋กœ, ACI ์ฅ ๋ชจ๋ธ์—์„œ ์ •๋งฅ ์ฒ ๋ถ„์„ ํˆฌ์—ฌํ•˜๊ณ  3์ผ ๋’ค ํ˜ˆ์ƒ‰์†Œ ์ˆ˜์น˜๊ฐ€ ํ˜ธ์ „๋˜์ง€ ์•Š์•˜๋Š”๋ฐ, ์ด๋Š” ๋งŒ์„ฑ ์—ผ์ฆ ์ƒํƒœ์—์„œ ์ฆ๊ฐ€ํ•ด ์žˆ๋˜ hepcidin์ด ์ฒ ๋ถ„ ํˆฌ์•ฝ์œผ๋กœ ์ธํ•ด ๋” ์ฆ๊ฐ€ํ•œ ๊ฒƒ๊ณผ ์—ฐ๊ด€๋˜์–ด ์žˆ์„ ์ˆ˜ ์žˆ๋‹ค. ์‹ค์ œ๋กœ ์ฒ ๋ถ„ ํˆฌ์•ฝ ํ›„ ๊ฐ„์—์„œ hepcidin ๋ฐ ferritin์˜ ์œ ์˜ํ•œ ์ฆ๊ฐ€๊ฐ€ ํ™•์ธ๋˜์—ˆ๋‹ค. ์ฒ ๋ถ„ ํˆฌ์•ฝ ํ›„ hepcidin์˜ ๋ฐœํ˜„ ์ฆ๊ฐ€๋Š” SMAD1/5 ์™ธ์— STAT-3 ๊ด€๋ จ ๊ฒฝ๋กœ์˜ ํ™œ์„ฑํ™”์™€๋„ ๊ด€๋ จ์ด ์žˆ์Œ์„ ๊ด€์ฐฐํ•  ์ˆ˜ ์žˆ์—ˆ๋Š”๋ฐ, ์ฒ ๋ถ„ ํˆฌ์—ฌ๋กœ ์‚ฐํ™” ์ŠคํŠธ๋ ˆ์Šค ์ง€ํ‘œ๋“ค์ด ์ฆ๊ฐ€ํ•œ ๊ฒƒ๊ณผ ์—ฐ๊ด€์„ฑ์ด ์žˆ์„ ๊ฒƒ์œผ๋กœ ์ƒ๊ฐ๋œ๋‹ค. ์ฒ ๋ถ„ ํˆฌ์•ฝ ํ›„ ์‹ ์žฅ EPO ๋ฐœํ˜„ ๋ฐ ํ˜ˆ์ฒญ ERFE ๋†๋„๊ฐ€ ๋™์‹œ์— ๊ฐ์†Œํ•˜๋Š” ๊ฒƒ์€ ACI ์กฐ๊ฑด ํ•˜์—์„œ ์ถฉ๋ถ„ํ•œ ์ฒ ๋ถ„ ๋ณด์ถฉ์—๋„ ๋ถˆ๊ตฌํ•˜๊ณ  ํšจ๊ณผ์ ์ธ ์กฐํ˜ˆ ์ž‘์šฉ์„ ๋ฐฉํ•ดํ•˜๋Š” ์ ํ˜ˆ๊ตฌ ์กฐ์ ˆ ์ธ์ž๋“ค์˜ ๋ณต์žกํ•œ ์ƒํ˜ธ์ž‘์šฉ์ด ๋ฐœ์ƒํ•จ์„ ๋ณด์—ฌ์ค€๋‹ค. ์ด๋Ÿฌํ•œ ๊ฒฐ๊ณผ๋“ค์„ ๊ณ ๋ คํ•  ๋•Œ ๋งŒ์„ฑ ์—ผ์ฆ ์ƒํƒœ์—์„œ ์ •๋งฅ ์ฒ ๋ถ„์ œ ํˆฌ์•ฝ์œผ๋กœ ๋นˆํ˜ˆ์„ ํšจ์œจ์ ์œผ๋กœ ์น˜๋ฃŒํ•˜๊ธฐ ์œ„ํ•ด์„œ๋Š” hepcidin๊ณผ EPO ์กฐ์ ˆ์„ ํ•จ๊ป˜ ๊ณ ๋ คํ•˜๋Š” ๊ฒƒ์ด ๋„์›€์ด ๋  ๊ฒƒ์œผ๋กœ ์ƒ๊ฐํ•œ๋‹ค. Anemia of chronic inflammation (ACI), also known as anemia of chronic disease, is the second most frequent form of anemia in hospitalized patients and a harbinger of adverse health outcomes. Hepcidin, the master regulator of iron homeostasis, is expressed mainly in the liver and induces the degradation of ferroportin, the sole iron exporter. Chronic inflammatory conditions lead to an increase in the levels of hepcidin, resulting in a sequestration of iron inside cells in the form of ferritin, and this hinders iron utilization for erythropoiesis despite sufficient iron stores in the body. However, anemia is often clinically treated with iron supplementation, regardless of the underlying cause, with varying results in patients with ACI. Changes in hepcidin levels and activity in ACI patients have not been fully elucidated, and understanding them may provide new insights for planning treatment strategies. Thus, the primary aim of this study was to establish an animal model of ACI that resembled clinical ACI and use it to investigate changes in hepcidin and upstream regulatory pathways in the liver after intravenous (IV) iron supplementation. Additionally, we examined whether oxidative stress and concomitant changes in the major erythropoiesis-stimulating pathways involving erythropoietin (EPO) and erythroferrone (ERFE), was induced by iron supplementation. We also aimed to identify the role of signaling pathways upstream of hepcidin in HepG2 cells treated with iron using short interfering RNAs. ACI was induced in rats by intraperitoneal administration of Complete Freundโ€™s Adjuvant (CFA, 0.2 mg in oil, 3 times/2 weeks). Male Sprague Dawley rats (n = 30) were randomly assigned to 3 groups: control-saline (n = 10), CFA-saline (n = 10), and CFA-IV iron (n = 10). Rats showing a decline in hemoglobin (Hb) levels >2 g/dL from baseline at 2 weeks after CFA administration were designated as ACI rats. ACI rats received iron (20 mg/kg of iron isomaltoside, CFA-IV iron) or vehicle (CFA-saline) intravenously. Three days after which changes in hematologic parameters, inflammatory cytokine levels, iron profiles, expression of proteins involved in signaling pathways upstream of hepcidin transcription, and iron metabolism gene expression were evaluated in the liver. ACI rats with anemia showed a concomitant increase in the expression of inflammatory mediators (i.e., interleukin [IL]-1ฮฒ, IL-6, tumor necrosis factor-ฮฑ [TNF-ฮฑ]) and reactive oxygen species (ROS). Three days after IV iron administration, Hb levels in ACI rats did not fully recover to the corresponding baseline values. Hepcidin levels in the liver of ACI rats were upregulated with a concomitant increase in ferritin levels in the liver compared to those in CFA-saline rats. Iron supplementation also induced an increase in ROS-generating NADPH oxidase (NOX)-2, NOX-4, and superoxide dismutase in the liver compared to those in CFA-saline rats. In ACI rats, activity of the IL-6/signal transducer and activator of transcription-3 (IL-6/STAT-3) pathway and the bone morphogenetic protein/Sma mothers against decapentaplegic (BMP/SMAD) pathway were increased in the liver compared to those in vehicle treated rats. IV iron supplementation further increased SMAD1/5 phosphorylation and STAT-3 phosphorylation in CFA-IV iron rats compared to those in CFA-saline rats, while there was no difference in IL-6 expression between both groups. Iron caused phosphorylation of STAT-3 and SMAD1/5 in HepG2 cells, and knockdown of STAT-3 and SMAD1/5 using short interfering RNAs in HepG2 cells was found to be associated with diminished iron-induced upregulation in hepcidin transcription compared to that in the corresponding control cells. IV iron supplementation was also associated with decrease in EPO mRNA expression in the kidney and serum ERFE concentration in CFA-IV iron rats compared to those in control-saline rats. In conclusion, in this rat model of ACI, IV iron administration did not effectively ameliorate anemia within 3 days despite an increase in ferritin levels in the liver, which might be related to an additional increase in hepcidin levels that was already upregulated under chronic inflammatory conditions. Both STAT-3 and SMAD1/5 phosphorylation were found to be associated with hepcidin upregulation after IV iron treatment, and this is potentially linked to iron-induced oxidative stress. Concurrent reductions in renal EPO expression and serum ERFE activity after IV iron supplementation imply a complex interplay between erythroid regulatory molecules that hinders effective erythropoiesis despite sufficient iron supplementation under ACI conditions. These results provide primary evidence regarding the importance of hepcidin regulation and EPO availability in increasing the efficacy of IV iron supplementation for the treatment of anemia under chronic inflammatory conditions.open๋ฐ•

    A Case of an apartment Village community under transformation and its resident participation structure

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ํ™˜๊ฒฝ๋Œ€ํ•™์› : ํ™˜๊ฒฝ๋Œ€ํ•™์› ํ™˜๊ฒฝ๊ณ„ํšํ•™๊ณผ ๋„์‹œ๋ฐ์ง€์—ญ๊ณ„ํš ์ „๊ณต, 2016. 2. ๊น€๊ด‘์ค‘.๋ณธ ์—ฐ๊ตฌ๋Š” ๊ณต๋™์ฒด์˜ ํ•ด์ฒด, ๋„์‹œ ๋ฌธ์ œ์˜ ๋ฐœ์ƒ, ์ „ํ†ต์  ๋„์‹œ ๊ด€๋ฆฌ ๋ฐฉ์‹์˜ ๋ณ€ํ™” ๋“ฑ์˜ ๋Œ€์•ˆ์œผ๋กœ ๋“ฑ์žฅํ•œ ๋งˆ์„๊ณต๋™์ฒด๋ฅผ ๋‹ค๋ฃฌ๋‹ค. ๋งˆ์„๊ณต๋™์ฒด๋Š” ๊ทธ ๊ฒƒ์ด ๊ฐ€์ง„ ๊ธฐ๋Œ€ํšจ๊ณผ์™€ ๊ฒฐ๊ณผ์ ์ธ ์ธก๋ฉด์—์„œ ์ฃผ๋ชฉ๋ฐ›์•„์™”๋‹ค. ๋ฐ˜๋ฉด ๋งˆ์„๊ณต๋™์ฒด๊ฐ€ ์ด๋ฃจ์–ด์ง€๋Š” ๊ณผ์ •์€ ์ƒ๋Œ€์ ์œผ๋กœ ๋งŽ์€ ๊ด€์‹ฌ์„ ๋ฐ›์ง€ ๋ชปํ•ด์™”๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ๋งˆ์„๊ณต๋™์ฒด๋Š” ๊ทธ ์ž์ฒด๊ฐ€ ๊ฒฐ๊ณผ์ด๊ธฐ ๋ณด๋‹ค๋Š” ์ด๋ฃจ์–ด์ง€๋Š” ๊ณผ์ •์ด ์ž์—ฐ์Šค๋Ÿฝ๊ฒŒ ๊ฒฐ๊ณผ๋ฅผ ์ˆ˜๋ฐ˜ํ•œ๋‹ค. ๋ณธ ์—ฐ๊ตฌ๋Š” ๊ฒฝ๊ธฐ๋„ ํ’€์žŽ์‹œ์˜ ์†Œ๋‚˜๋ฌด๋งˆ์„๊ณต๋™์ฒด๋ฅผ ์‚ฌ๋ก€๋กœ ๋งˆ์„๊ณต๋™์ฒด์˜ ์‹œ๊ฐ„๋ณ„ ์ „๊ฐœ๊ณผ์ •๊ณผ ํ˜„์žฌ ํ™œ๋™์—์„œ ๋“œ๋Ÿฌ๋‚˜๋Š” ์ฐธ์—ฌ์˜ ํ˜•ํƒœ์™€ ํŠน์ง•, ๊ทธ๋ฆฌ๊ณ  ๊ตฌ์กฐ์— ๋Œ€ํ•ด ๋‹ค๋ฃจ๊ณ ์ž ํ•œ๋‹ค. ๋ง๋ถ™์—ฌ ํ˜„์žฌ์˜ ์†Œ๋‚˜๋ฌด ๋งˆ์„๊ณต๋™์ฒด๊ฐ€ ์–ด๋– ํ•œ ๋„์‹œ ๊ณ„ํš์  ํ•จ์˜๋ฅผ ์ œ์‹œํ•˜๋Š” ์ง€ ๋ฐœ๊ฒฌํ•ด๋ณด๋ ค๊ณ  ํ•œ๋‹ค. ๋จผ์ € ์†Œ๋‚˜๋ฌด๋งˆ์„๊ณต๋™์ฒด ์ฃผ๋ฏผ ์ง‘๋‹จ ๊ตฌ์„ฑ์˜ ๋ณ€ํ™”๊ฐ€ ์‹œ๊ธฐ์™€ ๊ด€๊ณ„์—†์ด ๋งˆ์„์— ๊ฐœ์ž…ํ•˜๋Š” ์ •์ฑ…์˜ ๋ณ€ํ™”๋กœ ์ด์–ด์ง์„ ๋ฐœ๊ฒฌํ•˜์—ฌ ์ด๋ฅผ ์ค‘์‹ฌ์œผ๋กœ ์ „๊ฐœ๊ณผ์ •์„ ๊ธฐ์ˆ ํ•˜์˜€๋‹ค. 1๊ธฐ์—๋Š” ํ‰์ƒํ•™์Šต์‹œ๋ฒ”๋งˆ์„ ์‚ฌ์—…์„ ์ •์„ ํ†ตํ•ด ์ค‘๊ฐ„์ง€์›๋‹จ์ฒด๊ฐ€ ๋งˆ์„๊ณต๋™์ฒด๋ฅผ ํ˜•์„ฑ์„ ์ถ”์ง„ํ–ˆ๋‹ค. ์ผ๋ถ€ ๋งˆ์„ ์ฃผ๋ฏผ์ด ๋ฆฌ๋”๋กœ์„œ ๋งˆ์„์ง€๋„์ž๋กœ ์œก์„ฑ๋œ๋‹ค. 2๊ธฐ๋Š” ์‚ฌ์—… ์ง€์›์ด ์ข…๋ฃŒ๋˜์–ด 1๊ธฐ์˜ ์ฃผ์ถ•์œผ๋กœ ์ฐธ์—ฌํ•œ ์ฃผ๋ฏผ์ด ๋ชจ๋‘ ํ™œ๋™์„ ๊ทธ๋งŒ๋‘๋Š” ๋Œ€์‹  ๋งˆ์„ ๊ฐ•์‚ฌ ์ฃผ๋ฏผ ๋ช‡๋ช‡์„ ์ค‘์‹ฌ์œผ๋กœ ํ™œ๋™์ด ์ด๋ฃจ์–ด ์กŒ๋‹ค. ์ •์ฑ…์˜ ์ง€์›์€ ์—†์—ˆ๋‹ค. 3๊ธฐ๋Š” 2๊ธฐ์— ์ฐธ์—ฌํ•œ ์ฃผ๋ฏผ์˜ ํ™œ๋™์ด ์–ด๋ ค์›€์— ๋ด‰์ฐฉํ•˜์—ฌ 1๊ธฐ์— ์ฐธ์—ฌํ•œ ๋งˆ์„ ์ง€๋„์ž ์ฃผ๋ฏผ ๊ทธ๋ฃน์˜ ์ผ๋ถ€๊ฐ€ ๋ณต๊ท€ํ•˜์˜€๋‹ค. ์ด๋“ค์€ ์ ๊ทน์ ์œผ๋กœ ๋งˆ์„ ์‚ฌ์—…๊ณต๋ชจ์— ์ง€์›ํ•˜์—ฌ ๋งˆ์„๊ณต๋™์ฒด ํ™œ๋™์„ ์ง€์†ํ•˜๋ ค๊ณ  ํ•œ๋‹ค. 4๊ธฐ๋Š” ์ง€์› ์‚ฌ์—…์„ ํ†ตํ•ด ํ˜•์„ฑ๋œ ์ฃผ๋ฏผ ์†Œ๋ชจ์ž„์ด ๊ธฐ์กด์˜ ๋งˆ์„๊ณต๋™์ฒด ์ฐธ์—ฌ ์ง‘๋‹จ์— ํ•ฉ๋ฅ˜ํ•˜๊ฒŒ ๋˜์–ด ๋งˆ์„๊ณต๋™์ฒด์˜ ๊ทœ๋ชจ๊ฐ€ ํ™•์žฅ๋œ ์‹œ๊ธฐ์ด๋‹ค. ๋‹ค์Œ์œผ๋กœ๋Š” ๋งˆ์„ํšŒ์˜์™€ ์ถ•์ œ, ์—๋„ˆ์ง€ ์†Œ๋“ฑํ–‰์‚ฌ๋ฅผ ๊ด€์ฐฐํ•˜๊ณ  ๊ธฐ์ˆ ํ•˜์˜€์œผ๋ฉฐ, ๋งˆ์„ ์ฃผ๋ฏผ์˜ ์ฐธ์—ฌ์— ๋Œ€ํ•œ ์„ธ ๊ฐ€์ง€ ํŠน์ง•์„ ๋ถ„์„ํ•˜์˜€๋‹ค. ๋จผ์ € ๋งˆ์„๊ณต๋™์ฒด๋Š” ๋งˆ์„์—์„œ ์ •์ฑ…์˜ ์ง€์›์œผ๋กœ ๋งˆ์„ ํ™˜๊ฒฝ ๊ฐœ์„  ํ™œ๋™์„ ํ•˜๋Š” ํ˜น์€ ๊ทธ์— ๊ด€์‹ฌ์ด ์žˆ๋Š”, ์ผ๋ถ€์˜ ์ฃผ๋ฏผ์ด ์ฐธ์—ฌํ•˜๋Š” ๋งˆ์„ ์†Œ์ง‘๋‹จ์ด๋‹ค. ๋งˆ์„๊ณต๋™์ฒด๊ฐ€ ๋ณธ๋ž˜ ๋œปํ•˜๋Š” ๋ฐ”์™€ ๋‹ฌ๋ฆฌ ๋งˆ์„ ๋ฒ”์œ„์˜ ์ฃผ๋ฏผ ์ „์ฒด๋ฅผ ํฌ๊ด„ํ•˜์ง€ ์•Š๋Š”๋‹ค๊ณ  ๋ณด์ธ๋‹ค. ๊ทธ๋Ÿฌ๋ฏ€๋กœ ์†Œ๋‚˜๋ฌด ์•„ํŒŒํŠธ์˜ ๊ฑฐ์ฃผ๋ฏผ์€ ๋งˆ์„๊ณต๋™์ฒด ํ™œ๋™์„ ํ•˜๋Š” ๋งˆ์„๊ณต๋™์ฒด ๊ตฌ์„ฑ์›๊ณผ ๊ทธ๋ ‡์ง€ ์•Š์€ ์ฃผ๋ฏผ์œผ๋กœ ๊ตฌ๋ถ„ํ•ด ๋ณผ ์ˆ˜ ์žˆ๋‹ค. ๋‘ ๋ฒˆ์งธ ๋งˆ์„๊ณต๋™์ฒด ํ™œ๋™์„ ๊ด€์ฐฐํ•œ ๊ฒฐ๊ณผ ํ•˜๋‚˜์˜ ํ–‰์‚ฌ์—์„œ ๊ตฌ์„ฑ์›๋“ค์€ ๊ฐœ๋ณ„์ ์œผ๋กœ ๋‹ค๋ฅธ ์—ญํ• ์„ ๋งก๊ณ  ์žˆ์—ˆ๊ณ , ์ด๋Ÿฌํ•œ ์—ญํ• ์€ ๋‹ค๋ฅธ ํ–‰์‚ฌ์—์„œ๋„ ๋ฐ˜๋ณต์ ์œผ๋กœ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ํ™œ๋™์—์„œ ์ง‘๋‹จ ๋‚ด๋ถ€ ์—ญํ•  ๋ถ„๋‹ด์ด ์žˆ๋‹ค๊ณ  ๋ณด์˜€์œผ๋‚˜, ๋ช…์‹œ์ ์œผ๋กœ ์ •ํ•ด์ง„ ๊ฒƒ์€ ์•„๋‹ˆ๋‹ค. ์ด๋Š” ์ผ์˜ ์™„์ˆ˜๋ฅผ ์œ„ํ•˜์—ฌ ๊ตฌ์„ฑ์› ๊ฐ„ ์—ญํ• ์ด ๋ถ„ํ™”(ๅˆ†ๅŒ–)๋จ์„ ์˜๋ฏธํ•œ๋‹ค. ์„ธ ๋ฒˆ์งธ ๋งˆ์„๊ณต๋™์ฒด ๊ตฌ์„ฑ์›์€ ๋งˆ์„๊ณต๋™์ฒด์—์„œ ํ•˜์œ„์ง‘๋‹จ์„ ๊ตฌ์„ฑํ•˜๊ณ  ์žˆ๋‹ค. ๋ณธ ํ•˜์œ„์ง‘๋‹จ์€ ์—ญํ• , ํŠน์ง•, ์˜์‚ฌ๊ฒฐ์ •์—์˜ ์˜ํ–ฅ๋ ฅ์ด ๋ชจ๋‘ ์ƒ์ดํ•˜๊ฒŒ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ์ด์™€ ๋”๋ถˆ์–ด ์—ฐ๊ตฌ์ž๋Š” ๋งˆ์„๊ณต๋™์ฒด ํ™œ๋™์—์„œ ์ฃผ๋ฏผ์˜ ์ฐธ์—ฌ๊ฐ€ ๊ฐœ์ธ๋งˆ๋‹ค ๋‹ค๋ฅด๊ฒŒ ๋‚˜ํƒ€๋‚จ์— ์ฃผ๋ชฉํ•˜์˜€๋‹ค. ํ–‰์œ„๊ฐ€ ๋‘๋“œ๋Ÿฌ์ง€๊ฒŒ ๊ตฌ๋ถ„๋˜์–ด ๋‚˜ํƒ€๋‚œ ์ฃผ๋ฏผ์„ ๋Œ€์ƒ์œผ๋กœ ์ด๋“ค์˜ ์ฐธ์—ฌ๋ฅผ ์ดํ•ดํ•˜๊ณ ์ž ์‹ฌ์ธต ๋ฉด๋‹ด์„ ์ง„ํ–‰ํ•˜์˜€๋‹ค. ๊ทธ ๊ฒฐ๊ณผ ํŠน์ •ํ•œ ์—ญํ• ์„ ํ•˜๋Š” ๊ฐœ์ธ์ด ๋งˆ์„๊ณต๋™์ฒด ํ™œ๋™ ์ฐธ์—ฌ์— ๋ถ€์—ฌํ•˜๋Š” ์˜๋ฏธ๋Š” ๋ชจ๋‘ ๋‹ฌ๋ž๋Š”๋ฐ, ์ด๋Š” ๋งˆ์„๊ณต๋™์ฒด์˜ ์ฐธ์—ฌ์ •๋„ ๋ฐ ๋‚ด๋ถ€์˜ ์—ญํ• ๊ณผ ๊ด€๊ณ„๊ฐ€ ์žˆ๋‹ค๊ณ  ๋ณด์˜€๋‹ค. ๊ทธ๋Ÿผ์—๋„ ๋งˆ์„๊ณต๋™์ฒด์˜ ๊ตฌ์„ฑ์›์€ ๊ณตํ†ต์ ์œผ๋กœ ๋งˆ์„ํ™œ๋™์—์˜ ์ฐธ์—ฌ๋ฅผ ๋ด‰์‚ฌ๋กœ์„œ ์ƒ๊ฐํ•˜๊ณ  ์žˆ์Œ์„ ๋ฐœ๊ฒฌํ•˜์˜€๋‹ค. ์œ„์™€ ๊ฐ™์ด ๋งˆ์„ ํ™œ๋™๊ณผ ์‹ฌ์ธต ๋ฉด๋‹ด์—์„œ ๋„์ถœ๋œ ํŠน์ง•์„ ๋ฐ”ํƒ•์œผ๋กœ ์ฃผ๋ฏผ์˜ ์ฐธ์—ฌ๋ฅผ ์ƒˆ๋กญ๊ฒŒ ๊ตฌ์กฐํ™”ํ•˜์˜€๋‹ค. ๋งˆ์„๊ณต๋™์ฒด ์ฐธ์—ฌํ–‰์œ„์™€ ๋งก์€ ์—ญํ• ์„ ๊ธฐ์ค€์œผ๋กœ ์‚ผ์•„ ์ฃผ๋ฏผ ์ง‘๋‹จ์„ ๋Œ€ํ‘œ์ž, ์‹ค๋ฌด์ž, ์˜นํ˜ธ์ž, ์ด์šฉ์ž, ๋น„์ฐธ์—ฌ์ž์˜ ๋‹ค์„ฏ ์ธต์œ„๋กœ ๊ตฌ๋ถ„ํ–ˆ๋‹ค. ๋Œ€ํ‘œ์ž๋Š” ๋งˆ์„ํ•™๊ต์žฅ, ์—๋„ˆ์ง€์ ˆ์•ฝ๋งˆ์„์œ„์›์žฅ์œผ๋กœ ์ดˆ๊ธฐ ๋‹จ๊ณ„ ๋งˆ์„ ํ™œ๋™์„ ์ œ์•ˆ ๋ฐ ๋ฐœ์˜ํ•˜๋ฉฐ, ์ค‘์š”ํ•œ ์˜์‚ฌ๊ฒฐ์ •์„ ๋‚ด๋ฆฐ๋‹ค. ์‹ค๋ฌด์ž๋Š” ์ฝ”๋””๋„ค์ดํ„ฐ์™€ ๋ถ„๊ณผ์žฅ์œผ๋กœ ์ œ์•ˆ๋œ ์‚ฌ์—…์„ ๋ฐ”ํƒ•์œผ๋กœ ์‹ค์ œ ํ™œ๋™์„ ๊ธฐํšํ•˜๊ณ  ์šด์˜ํ•˜๋Š” ์ง‘๋‹จ์œผ๋กœ ์‹ค๋ฌด๋ฅผ ๋‹ด๋‹นํ•œ๋‹ค. ์˜นํ˜ธ์ž๋Š” ๋ด‰์‚ฌ์ž์™€ ๋งˆ์„๊ฐ•์‚ฌ๋กœ ๋ด‰์‚ฌํ™œ๋™์„ ํ†ตํ•ด ๋…ธ๋™๋ ฅ์„ ์ œ๊ณตํ•˜๋ฉฐ, ์‹ค๋ฌด์ž ์ง‘๋‹จ์˜ ํ™œ๋™์„ ์ง€์ง€ํ•œ๋‹ค. ์ด์šฉ์ž๋Š” ์ผํšŒ์ ์œผ๋กœ ๋งˆ์„๊ณต๋™์ฒด ํ™œ๋™์— ์ฐธ๊ฐ€ํ•˜๊ฑฐ๋‚˜, ๋งˆ์„๊ณต๋™์ฒด์— ์˜ํ•ด ๊ธฐํš๋œ ํ™œ๋™์„ ์ด์šฉํ•˜๋Š” ์•„ํŒŒํŠธ ๊ฑฐ์ฃผ๋ฏผ์ด๋‹ค. ๊ฐ ์ง‘๋‹จ์€ ๊ตฌ์„ฑ์› ์ˆ˜, ๋งˆ์„๊ณต๋™์ฒด์—์„œ์˜ ์—ญํ• , ์˜์‚ฌ๊ฒฐ์ •์— ๋ฏธ์น˜๋Š” ์˜ํ–ฅ๋ ฅ์˜ ์ •๋„, ์‹ค์ œ ํ–‰์œ„ ๋“ฑ์—์„œ ์ฐจ์ด๋ฅผ ๋ณด์ธ๋‹ค. ํ•œํŽธ ์ •์ฑ…์—์„œ ๋งˆ์„๊ณต๋™์ฒด๋Š” ๋‹ค์–‘ํ•œ ์˜๋ฏธ๋ฅผ ํฌ๊ด„ํ•œ๋‹ค. ํฌ๊ฒŒ ๋ณธ๋ž˜์  ์˜๋ฏธ์ธ ๊ตฌ์„ฑ์›์˜ ํ˜ธํ˜œ๊ด€๊ณ„ ์ถ”๊ตฌ๋ฟ๋งŒ ์•„๋‹ˆ๋ผ ๋งˆ์„ ํ™˜๊ฒฝ ๊ฐœ์„ ์„ ๋œปํ•˜๋Š” ๋งˆ์„๋งŒ๋“ค๊ธฐ์™€ ์ƒํ–ฅ์‹์˜ ๋„์‹œ ๊ด€๋ฆฌ ๋ฐ ์ฃผ๋ฏผ์ฐธ์—ฌ ๊ฑฐ๋ฒ„๋„Œ์Šค๋ฅผ ๋œปํ•˜๋Š” ์˜๋ฏธ๋กœ์„œ๋„ ์‚ฌ์šฉ๋œ๋‹ค. ๊ทธ๋Ÿฌ๋ฏ€๋กœ ํ˜„์žฌ ๋งˆ์„๊ณต๋™์ฒด ์‚ฌ์—…์˜ ์˜ˆ์‚ฐ ์ง€์› ๋Œ€์ƒ์ด ๋˜๋Š” ๋งˆ์„๊ณต๋™์ฒด์˜ ํ™œ์„ฑํ™”๋ฅผ ๋…ผํ•˜๊ธฐ ์œ„ํ•ด์„œ๋Š” ๊ทธ ๊ฒƒ์ด ํฌ๊ด„ํ•˜๋Š” ์˜๋ฏธ๋ฅผ ๊ตฌ๋ถ„ํ•˜์—ฌ ๊ฐ๊ฐ์— ๋งž๋Š” ๋ชฉ์ ์ด ๋‹ฌ์„ฑ๋˜๋Š” ์ง€ ํ™•์ธํ•จ์ด ํ•„์š”ํ•˜๋‹ค. ๋งˆ์„์—์„œ ๋งˆ์„๊ณต๋™์ฒด์˜ ํ™œ์„ฑํ™”๋Š” ํ˜ธํ˜œ๊ด€๊ณ„ ํ˜•์„ฑ๊ณผ ๋งˆ์„๋งŒ๋“ค๊ธฐ ๋‹ฌ์„ฑ์˜ ์ธก๋ฉด์—์„œ ์„ธ ๊ฐ€์ง€๋กœ ๊ฐœ๋…ํ™”ํ•˜์—ฌ ์‚ดํŽด๋ณด๋ ค๊ณ  ํ•œ๋‹ค. ์ฒซ ๋ฒˆ์งธ๋Š” ๊ณต๋™์ฒด ๋‚ด๋ถ€์—์„œ์˜ ํ™œ์„ฑํ™”, ๋‘ ๋ฒˆ์งธ๋Š” ๊ณต๋™์ฒด ๊ทœ๋ชจ์˜ ํ™•์žฅ์„ ํ†ตํ•œ ํ™œ์„ฑํ™”, ์„ธ ๋ฒˆ์งธ๋Š” ๋น„๊ตฌ์„ฑ์› ๊ฑฐ์ฃผ๋ฏผ ์ง‘๋‹จ์—์„œ์˜ ๋‹ฌ์„ฑ์„ ํ†ตํ•œ ํ™œ์„ฑํ™”์ด๋‹ค. ํ˜ธํ˜œ๊ด€๊ณ„ ์ธก๋ฉด์—์„œ ๋งˆ์„๊ณต๋™์ฒด๋Š” ๊ตฌ์„ฑ์› ์‚ฌ์ด์˜ ํ˜ธํ˜œ์„ฑ์„ ํ˜•์„ฑํ•œ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ๊ทœ๋ชจ์˜ ํ™•์žฅ์„ ํ†ตํ•œ ํ˜ธํ˜œ์„ฑ์˜ ํ™œ์„ฑํ™”๋Š” ์ž˜ ์ด๋ฃจ์–ด์ง€์ง€ ์•Š์œผ๋ฉฐ, ๋น„๊ตฌ์„ฑ์›์˜ ๊ฒฝ์šฐ ์ด๋ฒคํŠธ์„ฑ ์ผํšŒ์  ์ฐธ๊ฐ€๋กœ ์ฐธ์—ฌ๊ฐ€ ๊ธฐํš๋œ๋‹ค๋Š” ์ ์—์„œ ํ˜ธํ˜œ๊ด€๊ณ„ ํ˜•์„ฑ์˜ ์–ด๋ ค์›€์„ ๊ฒช๋Š”๋‹ค. ์ด์ œ ๋งˆ์„ ๋ฌธ์ œ ํ•ด๊ฒฐ์˜ ์ธก๋ฉด์—์„œ ๋ณด์ž. ๋งˆ์„๊ณต๋™์ฒด์˜ ๊ตฌ์„ฑ์›์€ ๋งˆ์„๋งŒ๋“ค๊ธฐ๋ฅผ ํ•œ๋‹ค. ๊ธฐ์กด์—๋Š” ๋งˆ์„๋งŒ๋“ค๊ธฐ์˜ ํ™œ์„ฑํ™”์— ๋Œ€ํ•ด ๋Œ€๊ฐœ ๋งˆ์„ ํ™œ๋™์—์„œ ๋ฆฌ๋”์˜ ์ค‘์š”์„ฑ์„ ๊ฐ•์กฐํ•ด ์™”๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ๋งˆ์„์—์„œ๋Š” ๋ฆฌ๋”๋ฟ๋งŒ ์•„๋‹ˆ๋ผ ๋ฆฌ๋”์˜ ์ง€๋„๋ฅผ ๋”ฐ๋ฅด๋Š” ์‹ค๋ฌด์ž์™€ ์˜นํ˜ธ์ž ์ง‘๋‹จ์˜ ํŒ”๋กœ์›Œ์‹ญ์ด ๋งˆ์„๊ณต๋™์ฒด ํ™œ๋™์— ๋งŽ์€ ๊ธฐ์—ฌ๋ฅผ ํ•˜๊ณ  ์žˆ์—ˆ๋‹ค. ํ•œํŽธ ๋งˆ์„๊ณต๋™์ฒด ๊ทœ๋ชจ์˜ ํ™•์žฅ์„ ํ†ตํ•œ ๋งˆ์„๋งŒ๋“ค๊ธฐ ํ™œ์„ฑํ™”๋Š” ์•ž์„  ์‚ฌ๋ก€์ฒ˜๋Ÿผ ์‰ฝ๊ฒŒ ๋‹ฌ์„ฑ๋˜์ง€ ์•Š๋Š”๋‹ค. ๋น„๊ตฌ์„ฑ์›์˜ ๋ณ€ํ™”๋ฅผ ํ†ตํ•œ ๋งˆ์„๋งŒ๋“ค๊ธฐ ํ™œ์„ฑํ™” ๋˜ํ•œ ์ผํšŒ์  ์ฐธ๊ฐ€์— ๋จธ๋ฌด๋ฅด๋Š” ๊ฒฝ์šฐ๊ฐ€ ๋งŽ์•„ ๋‹ฌ์„ฑ๋˜๊ธฐ ์–ด๋ ต๋‹ค๊ณ  ๋ณด์ธ๋‹ค. ๋งˆ์ง€๋ง‰์œผ๋กœ ์ฃผ๋ฏผ ์ฐธ์—ฌ๋ฅผ ์ด๋ฃจ๋Š” ๊ฑฐ๋ฒ„๋„Œ์Šค์˜ ์ถ•์œผ๋กœ์„œ ๋งˆ์„๊ณต๋™์ฒด๊ฐ€ ์ง€์†ํ•˜๊ณ  ์„ฑ์žฅํ•˜๋Š” ์ง€ ํ˜„์žฌ ์ƒํ™ฉ์„ ๋ฐ”ํƒ•์œผ๋กœ ์ดํ•ดํ•˜๋ ค๊ณ  ํ•œ๋‹ค. ๋งˆ์„๊ณต๋™์ฒด๊ฐ€ ์ž๋ฐœ์ ์œผ๋กœ ํ™œ๋™ํ•˜๋Š” ์ฃผ๋ฏผ์„, ์ฃผ๋ฏผ์˜ ์‹œ๋ฏผ์„ฑ ํ–ฅ์ƒ์„ ์ด๋ฃจ์–ด๋‚ด๋Š”๊ฐ€. ๋งˆ์„ ์ฃผ๋ฏผ์€ ๋งˆ์„๊ณต๋™์ฒดํ™œ๋™ ์ฐธ์—ฌ๋ฅผ ๋ด‰์‚ฌ๋กœ์„œ ์ธ์‹ํ•œ๋‹ค. ๋ด‰์‚ฌ๋Š” ๊ทธ ๊ฒƒ์˜ ๋Œ€์ƒ์ด ์กด์žฌํ•  ๋•Œ ์ด๋ฃจ์–ด์ง„๋‹ค. ๊ทธ๋Ÿฌ๋ฏ€๋กœ ๋งˆ์„ ์ฃผ๋ฏผ์€ ๋งˆ์„ ์‚ฌ์—…์„ ์ˆ˜๋ฐ˜ํ•œ ๋งˆ์„๊ณต๋™์ฒด ํ™œ๋™์„ ๋งˆ์„์„ ์œ„ํ•œ ํฌ์ƒ, ํ—Œ์‹ ์˜ ๊ด€์ ์—์„œ ์ดํ•ดํ•œ๋‹ค๊ณ  ๋ณด์ธ๋‹ค. ๋‹ค์‹œ ๋งํ•˜๋ฉด ๋ด‰์‚ฌ์˜ ๋Œ€์ƒ์œผ๋กœ์„œ ์˜ˆ์‚ฐ ์ง€์›์ด ์ข…๋ฃŒ๋  ๊ฒฝ์šฐ ์ฃผ๋ฏผ์˜ ํ™œ๋™์€ ์ž์—ฐ์Šค๋Ÿฝ๊ฒŒ ๋์„ ๋งบ๊ธฐ๋„ ํ•œ๋‹ค. ์†Œ๋‚˜๋ฌด๋งˆ์„์—์„œ๋Š” ๋งˆ์„ ๋‚ด ๊ฐˆ๋“ฑ, ์—ญ๋Ÿ‰์˜ ๋ถ€์กฑ ๋“ฑ ๋„๋“œ๋ผ์ง€๋Š” ๋ถ„๋ช…ํ•œ ๋ฌธ์ œ๋Š” ์กด์žฌํ•˜์ง€ ์•Š์•˜์œผ๋ฉฐ, ํ™œ๋™์˜ ์ข…๋ฃŒ๋Š” ์ž์—ฐ์Šค๋Ÿฌ์šด ์ˆ˜์ˆœ์œผ๋กœ ์ดํ•ด๋˜์—ˆ๋‹ค. ๊ทธ๋Ÿผ์—๋„ ๋งˆ์„๊ณต๋™์ฒด ํ™œ๋™์ด ์ง€์†๋˜๋Š” ๋™์ธ์€ ๋งˆ์„๊ณต๋™์ฒด ํ™œ๋™์ด ์ฐธ์—ฌ์ž์˜ ๊ฐœ์ธ์  ์„ฑ์žฅ๊ณผ ์ดํ•ด๊ด€๊ณ„์— ๋งŽ์€ ์˜ํ–ฅ์„ ์ค„ ๋•Œ๋ผ๊ณ  ๋ณด์ธ๋‹ค. ๋‚˜์•„๊ฐ€ ๋ณธ ์—ฐ๊ตฌ๋Š” ๋งˆ์„๊ณต๋™์ฒด๋Š” ์˜๋ฏธ๊ฐ€ ๋ช…๋ฃŒํ•˜๊ฒŒ ๊ตฌ๋ถ„๋˜์–ด ์ดํ•ด๋  ํ•„์š”๊ฐ€ ์žˆ์œผ๋ฉฐ, ๋งˆ์„๊ณต๋™์ฒด ํ™œ๋™์—์„œ ์ฃผ๋ฏผ์˜ ์ง€์†์ ์ธ ์ฐธ์—ฌ๋ฅผ ์œ„ํ•ด์„œ๋Š” ์ผํšŒ์  ์„ฑ๊ฒฉ์˜ ์ฐธ๊ฐ€๋Š” ํšจ๊ณผ๋ฅผ ๊ฑฐ๋‘๊ธฐ ์–ด๋ ต๋‹ค๋Š” ์ ์„ ๋งํ•œ๋‹ค. ๋˜ํ•œ ๋งˆ์„๊ณต๋™์ฒด ๋ฆฌ๋” ์™ธ ์‹ค๋ฌด์žยท์˜นํ˜ธ์ž ๋“ฑ ๋ฆฌ๋”๊ฐ€ ์•„๋‹Œ ์ฃผ๋ฏผ์˜ ์—ญํ• ๊ณผ ๊ทธ๋“ค์˜ ์ค‘์š”์„ฑ์— ์ฃผ๋ชฉํ•  ํ•„์š”๊ฐ€ ์žˆ์Œ์„ ๋ฐํžŒ๋‹ค. ๋”๋ถˆ์–ด ์ฃผ๋ฏผ์˜ ๋งˆ์„๊ณต๋™์ฒด ํ™œ๋™ ์ค‘๋‹จ์€ ํŠน์ •ํ•œ ๊ณ„๊ธฐ์— ๊ธฐ์ธํ•˜์ง€ ์•Š๊ณ  ์ง€์› ์‚ฌ์—… ๊ธฐ๊ฐ„์— ๋งž์ถ˜ ์ž์—ฐ์Šค๋Ÿฌ์šด ํ–‰๋™์ด๋ผ๋Š” ์ ์„ ๋‹ค๋ฃฌ ๋ฐ์„œ ๋ณธ ์—ฐ๊ตฌ์˜ ์˜๋ฏธ๊ฐ€ ์žˆ๋‹ค.โ… . ์„œ๋ก  1 1. ์—ฐ๊ตฌ์˜ ๋ฐฐ๊ฒฝ ๋ฐ ๋ชฉ์  1 2. ์—ฐ๊ตฌ์˜ ๋Œ€์ƒ์ง€ 3 1) ์†Œ๋‚˜๋ฌด์•„ํŒŒํŠธ 3 2) ์†Œ๋‚˜๋ฌด๋งˆ์„๊ณต๋™์ฒด 6 3. ์—ฐ๊ตฌ์˜ ๋ฐฉ๋ฒ• 10 1) ์ฐธ์—ฌ๊ด€์ฐฐ 10 2) ์‹ฌ์ธต๋ฉด๋‹ด 12 โ…ก. ์„ ํ–‰์—ฐ๊ตฌ ๊ฒ€ํ†  14 1. ๋งˆ์„๊ณต๋™์ฒด ๊ฐœ๋…์˜ ํ˜ผ๋ž€ 14 1) ๊ณต๋™์ฒด๋Š” ๋ฌด์—‡์ธ๊ฐ€ 15 2) ๋งˆ์„์€ ๋ฌด์—‡์ธ๊ฐ€ 18 3) ๋งˆ์„๊ณต๋™์ฒด์˜ ์˜๋ฏธ 19 2. ํ˜„ ์ •์ฑ…์—์„œ์˜ ๋งˆ์„๊ณต๋™์ฒด 20 1) ํ˜ธํ˜œ๊ด€๊ณ„์˜ ํ˜•์„ฑ 20 2) ๋งˆ์„๋งŒ๋“ค๊ธฐ 22 3) ์ฃผ๋ฏผ์ฐธ์—ฌ๊ฑฐ๋ฒ„๋„Œ์Šค 24 3. ์ฐธ์—ฌ์™€ ๋ด‰์‚ฌ์˜ ๊ฐœ๋… 25 1) ์ฐธ์—ฌ์˜ ๊ฐœ๋…๊ณผ ๊ตฌ๋ถ„ 25 2) ๋ด‰์‚ฌ์˜ ๊ฐœ๋… 27 โ…ข. ์†Œ๋‚˜๋ฌด ๋งˆ์„๊ณต๋™์ฒด์˜ ์ „๊ฐœ๊ณผ์ • 29 1. ์†Œ๋‚˜๋ฌด ๋งˆ์„๊ณต๋™์ฒด์˜ ์ „๊ฐœ๊ณผ์ • 31 1) 1๊ธฐ : ์ •๋ถ€ ์ฃผ๋„์˜ ๋งˆ์„๊ณต๋™์ฒด ์œก์„ฑ๊ณผ ๋งˆ์„์ง€๋„์ž ์ฃผ๋ฏผ 31 2) 2๊ธฐ : ์ž๋ฐœ์  ๋งˆ์„ํ•™๊ต ์šด์˜๊ณผ ๋งˆ์„๊ฐ•์‚ฌ ์ฃผ๋ฏผ 38 3) 3๊ธฐ : ๋งˆ์„์ง€๋„์ž ์ฃผ๋ฏผ์˜ ๋ณต๊ท€์™€ ์ง€์›์‚ฌ์—… ๊ณต๋ชจ 44 4) 4๊ธฐ : ์ƒˆ๋กœ์šด ์ฃผ๋ฏผ ์ง‘๋‹จ์˜ ํ˜•์„ฑ๊ณผ ์ฐธ์—ฌ 49 โ…ฃ. ์†Œ๋‚˜๋ฌด ๋งˆ์„๊ณต๋™์ฒด ์ฃผ๋ฏผ์˜ ์ฐธ์—ฌ ํ–‰์œ„ 58 1-1. ์†Œ๋‚˜๋ฌด ๋งˆ์„๊ณต๋™์ฒด์˜ ์ฐธ์—ฌ 58 1) ๋งˆ์„ ํšŒ์˜์˜ ์ฐธ์—ฌ 58 2) ๋งˆ์„ ์ถ•์ œ์˜ ์ฐธ์—ฌ 60 3) ์—๋„ˆ์ง€ ์†Œ๋“ฑํ–‰์‚ฌ์˜ ์ฐธ์—ฌ 65 1-2. ์†Œ๋‚˜๋ฌด ๋งˆ์„๊ณต๋™์ฒด ์ฃผ๋ฏผ์˜ ์ฐธ์—ฌ 68 1) ์—๋„ˆ์ง€์ ˆ์•ฝ๋งˆ์„์œ„์›์žฅ๋งˆ์„ํ•™๊ต ๊ต์žฅ ์™•๋Œ€ํ‘œ 68 2) ๋งˆ์„ํ•™๊ต ์ฝ”๋””๋„ค์ดํ„ฐ ํ™์ฝ”๋”” 72 3) ์—๋„ˆ์ง€์ ˆ์•ฝ๋งˆ์„ ์ฝ”๋””๋„ค์ดํ„ฐ ์ •์‹ ์ž… 77 4) ๋ถ์นดํŽ˜ ๋ด‰์‚ฌ์ž ๊น€๋„์„œ 81 5) ๋งˆ์„ํ•™๊ต ํ”„๋กœ๊ทธ๋žจ ์ˆ˜๊ฐ•์ž ๋ฐ•์„œ๋ฆผ 86 2. ์†Œ๋‚˜๋ฌด ๋งˆ์„์—์„œ์˜ ์ฐธ์—ฌ๊ตฌ์กฐ 89 1) ์†Œ๋‚˜๋ฌด ๋งˆ์„๊ณต๋™์ฒด ํ™œ๋™์˜ ํŠน์ง• 89 2) ์ฃผ๋ฏผ์˜ ์ฐธ์—ฌ๊ตฌ์กฐ 95 โ…ค. ์†Œ๋‚˜๋ฌด๋งˆ์„ ์ฃผ๋ฏผ์˜ ์ฐธ์—ฌ ํ•ด์„ 99 1. ์ •์ฑ…์—์„œ์˜ ์†Œ๋‚˜๋ฌด ๋งˆ์„๊ณต๋™์ฒด 99 1) ํ˜ธํ˜œ๊ด€๊ณ„ ํ˜•์„ฑ 99 2) ์ปค๋ฎค๋‹ˆํ‹ฐ ํ™˜๊ฒฝ์˜ ๊ฐœ์„  104 3) ์ฃผ๋ฏผ์ฐธ์—ฌ ๊ฑฐ๋ฒ„๋„Œ์Šค 109 โ…ฅ. ๊ฒฐ๋ก  111 1. ์—ฐ๊ตฌ์˜ ์š”์•ฝ ๋ฐ ๊ฒฐ๋ก  111 ์ฐธ๊ณ ๋ฌธํ—Œ 115 Abstract 119Maste
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