크라프트 리그닌의 유동화제 사용을 위한 설포메틸레이션 반응 연구

학위논문 (석사)-- 서울대학교 대학원 : 농업생명과학대학 산림과학부, 2018. 2. 최인규.크라프트 펄핑 공정으로부터 생산되는 많은 양의 크라프트 리그닌은 연소과정을 통해 태워지고 있다. 그러나, 크라프트 리그닌의 고부가가치화의 가능성이 제시되고 있다. 설파이트 펄핑으로부터 생산되는 리그노설포네이트는 시멘트 첨가제로 사용되고 있지만, 설파이트 펄핑이 크라프트 펄핑으로 대체되고 있기 때문에 생산량이 한정적이다. 이러한 이유로 크라프트 리그닌의 화학적 개질을 통해 리그노설포네이트를 대체하려는 연구가 많이 진행되고 있다. 본 연구에서는 formaldehyde와 sodium sulfite를 사용하여 크라프트 리그닌의 sulfomethylation을 다양한 조건 하에 진행하였다. 용매는 sodium hydroxide를 사용하였다. 그 후에 최종 pH를 1M 황산용액을 사용하여 조절하였고, 12000 rpm으로 15분동안 원심분리를 하여 고상과 액상을 분리하였다. Sulfomethylation은 최종 pH (7, 5, 2), 반응온도(80, 100, 120℃), 반응시간(1, 3, 5, 8, 11시간), 리그닌 대비 투입 시약 비율(0.225, 0.45, 0.9, 1.2:1)에 따라 다르게 진행이 되었다. Particle charge detector와 적정제로 polydiallyldimethylammonium (PolyDADMAC)를 사용하여 sulfomethylation된 크라프트 리그닌의 전하밀도를 측정하였다. 그 후, 동결건조를 통해 건조된 시료를 얻었다. FT-IR 분석법으로 리그닌의 작용기변화를 확인하였고, guaiacyl과 syringyl 구조의 비율은 31P-NMR로 측정하였다. 또한, 설포네이트의 함량 비교를 위해 원소분석을 실시하였고, 이러한 분석을 통해 개질 조건에 따른 sulfomethylation의 특성을 비교하였다. 최대 전하밀도를 나타내는 조건은 최종pH 5, 반응온도 100℃, 반응시간 5시간, 리그닌 대비 투입 시약 비율 0.9:1이었다. 반면, 최종 pH 5, 반응온도 100℃, 반응시간 3시간, 리그닌 대비 투입 시약 비율 0.45:1일 때, 시멘트 유동성이 최대였다. 전하밀도가 증가할수록 시멘트 유동성이 증가할 것이라고 예상했지만, 전하밀도와 시멘트 유동성의 경향은 일치하지 않았다. 또한, 시료의 황 함량과 전하밀도, 시멘트 유동성과의 경향도 일치하지 않았다. 몇몇 연구에 따르면, 높은 분자량, 낮은 전하밀도, 비교적 긴 사실구조를 가진 polycarboxylate와 낮은 분자량과 높은 전하밀도를 가진 sulfonated naphthalene formaldehyde condensate(SNFC)과 비교하였다. 그 결과, 시멘트 유동성은 polycarboxylate를 사용하였을 때 더 좋았다. 더 나아가, 리그노설포네이트를 분자량마다 나누어 시멘트 유동성을 분석한 결과, 분자량과 시멘트 유동성은 비례하지 않았다. 전하밀도와 분자량이 시멘트 유동성과 비례관계가 아닌 것을 고려해보았을 때, 긴 사슬구조가 시멘트 유동성의 핵심 인자라고 사료된다. 리그닌 구성단위의 반응에 대한 영향을 조사하기 위해, 침엽수 크라프트 리그닌을 활엽수 크라프트 리그닌과 같은 반응 조건으로 sulfomethylation을 하였다. Sulfomethylation이 된 침엽수 크라프트 리그닌이 활엽수 크라프트 리그닌보다 더 높은 전하밀도와 시멘트 유동성을 나타내었다.The large amount of kraft lignin has been produced from kraft pulping and incinerated to be converted to energy. However, kraft lignin has a possibility to be used as more value-added material via chemical modification. Lignosulfonate produced by sulfite pulping is used as a superplasticizer, but the production of lignosulfonate has been dwindled because sulfite pulping has been substituted to kraft pulping. Therefore, there are a lot of efforts to substitute lignosulfonate to kraft lignin via a variety of chemical modification. In this study, sulfomethylation of kraft lignin was conducted by using formaldehyde and sodium sulfite in sodium hydroxide solvent with various reaction conditions. And then, final pH was adjusted with sulfuric acid (1 M) followed by centrifugation (12000 rpm, 15 min) to separate liquid and solid phases. Dried-solid sample was obtained by freeze-drying. Sulfomethylation of kraft lignin was conducted at final pH (7, 5 and 2), reaction temperature (80, 100 and 120℃), reaction time (1, 3, 5, 8 and 11 h), the dosage molar ratio of reagents (formaldehyde and sodium sulfite) to lignin (0.225, 0.45, 0.9 and 1.2:1). A particle charge detector (PCD) was utilized to measure charge density of the sulfomethylated kraft lignin by using a titrant (polydiallyldimethylammonium, PolyDADMAC). By fourier-transform infrared (FT-IR) spectroscopy analysis, the changed functional group on lignin could be examined, and the different ratio of guaiacyl and syringyl group could be investigated by phosphorus-31 nuclear magnetic resonance (31P-NMR). Furthermore, elementary analysis was utilized to compare the content of sulfonate. Through these analyses, the characteristics of sulfomethylated lignin under different reaction conditions were compared. As a result of this study, the reaction condition for the highest charge density was determined as pH 5 for final pH, 100℃ for reaction temperature, 5 h for reaction time and 0.9:1 for the dosage molar ratio of reagents to lignin. On the other hand, the maximum fluidity of cement was obtained at pH 5 for final pH, 100℃ for reaction temperature, 3 h for reaction time and 0.45:1 for the dosage molar ratio of reagents to lignin. It was anticipated that more charge density made workability of cement increase, but the tendency between charge density and fluidity of cement was not corresponded. Moreover, there was not proportional tendency among the content of sulfur, charge density and fluidity of cement. According to similar studies, polycarboxylate which had high molecular weight, low charge density and longer chain structure was compared to sulfonated naphthalene formaldehyde condensate (SNFC), which had low molecular weight and high charge density. As a result, cement fluidity was better in case of polycarboxylate. Moreover, the separation of lignosulfonate with different molecular weight was carried out, and viscosity of cement paste was not proportional to molecular weight. Considering charge density and molecular weight were not in proportional relation with fluidity of cement, longer chain structure may have been regarded as the key factor for high fluidity of cement. To investigate the influence of constituent unit of lignin in sulfomethylation, softwood kraft lignin (SKL) was sulfomethylated in same reaction condition and compared to hardwood kraft lignin (HKL). SKL which had more guaiacyl group indicated higher charge density and fluidity of cement than HKL.1. Introduction 1 1.1. Lignin & technical lignin 1 1.2. Lignin as a superplasticizer 4 1.3. Obstacles of technical lignin 6 1.4. Objectives 7 2. Literature reviews 9 2.1. Precipitation of kraft lignin 9 2.2. Modification of kraft lignin 10 2.3. Sulfomethylation & sulfonation of technical lignin for a superplasticizer 11 3. Materials & methods 13 3.1. Materials 13 3.2. Sulfomethylation of kraft lignin 13 3.3. The measurement of fluidity of cement 15 3.4. Characteristics of sulfomethylated kraft lignin 15 3.4.1. Charge density analysis 15 3.4.2. Solubility of sulfomethylated kraft lignin in water 16 3.4.3. FT-IR spectrometer 16 3.4.4. Gel permeation chromatography (GPC) 16 3.4.5. 31P-NMR analysis 17 3.4.6. Elementary analysis 17 4. Results & discussion 19 4.1. Analysis of salts produced by side reaction 19 4.1.1. Comparison between SHKL with and without dialysis 19 4.1.2. The analysis of unreacted salts 25 4.2. Effect of each factor to charge density 27 4.2.1. Fianl precipitating pH 27 4.2.2. Reaction temperature 31 4.2.3. Reaction time 33 4.2.4. The dosage molar ratio of reagents to lignin 35 4.3. The reaction condition for the highest fluidity of cement 37 4.4. The relation among sulfur content, charge density and fluidity of cement 42 4.5. Comparison between SKL & HKL 48 4.5.1. Analysis of unreacrted SKL & HKL 48 4.5.2. Comparison of unreacted and sulfomethylated SKL & HKL 53 4.6. Comparison between SHKL & commercial lignosulfonate 57 5. Conclusion 61 6. References 63Maste

The role of metastasis-directed therapy and local therapy of the primary tumor in the management of oligometastatic prostate cancer

Oligometastasis has been proposed as an intermediate stage of cancer spread between localized disease and widespread metastasis. Oligometastatic malignancy is now being diagnosed more frequently as the result of improvements in diagnostic modalities such as functional imaging. The importance of oligometastasis in managing metastatic prostate cancer is that it is possible to treat with a curative aim by metastasis-directed or local therapy in selected patients. Many studies have shown that these aggressive treatments lead to improved survival in other oligometastatic malignancies. However, few studies have shown definitive benefits of metastasis-directed or local therapy in oligometastatic prostate cancer. Review of the available studies suggests that stereotactic radiotherapy (RT) of metastatic lesions in oligorecurrent disease is a feasible and safe modality for managing oligometastatic prostate cancer. Also, stereotactic RT can delay the start of androgen deprivation therapy. Many retrospective studies of metastatic prostate cancer have shown that patients undergoing local therapy seem to have superior overall and cancer-specific survival compared with patients not receiving local therapy. Ongoing prospective randomized trials would be helpful to evaluate the role of local therapy in oligometastatic prostate cancer.ope

Recent global trends in testicular cancer incidence and mortality

Testicular cancer (TCa) has a relatively rare incidence and mortality, but has not been thoroughly evaluated. We analyzed global variations and recent trends in TCa incidence and mortality.Age-standardized rates (ASRs) of TCa incidence and mortality were retrieved from the GLOBOCAN 2012 database. Temporal patterns were assessed using data obtained from the Cancer Incidence in Five Continents (volumes I-X) and World Health Organization Mortality databases. The incidence and mortality trends over the last 10 years were analyzed using join point analysis.Western and Northern Europe had the highest incidence of TCa (ASR = 8.7 and 7.2, respectively), with most countries showing an increase in incidence rates except for China, which had a stable incidence. Incidence rates were markedly increased in Southern European countries (average annual percent change of 6.8% in Croatia and 6.1% in Spain) but were attenuated in western Europe. The highest mortality rates were observed in western Asia (ASR = 0.7), with most countries showing a decrease in mortality.While the incidence of TCa has increased, mortality from TCa has decreased in most countries. More socioeconomically developed countries had a higher incidence of TCa with lower mortality.ope

Nephron-Sparing Approaches in Upper Tract Urothelial Carcinoma: Current and Future Strategies

Upper tract urothelial carcinoma (UTUC) is a relatively rare cancer, and much of the approach to treatment has been derived from strategies employed in treating bladder cancer. Radical nephroureterectomy (RNU) is regarded as the gold standard treatment for UTUC. However, due to potential complications, such as renal function impairment, that can affect oncologic outcomes, the demand for nephron-sparing treatment to effectively treat cancer while preserving renal function has increased. As a result, various treatment methods for low-grade, low-volume UTUC, such as segmental ureterectomy, endoscopic resection, and intraluminal therapy, have been attempted and reported. Although these treatment modalities have exhibited acceptable oncological results, further studies are required. In the future, the introduction of new technologies, such as improved diagnostic and surgical equipment, and new drug delivery systems, could enhance the effectiveness of nephron-sparing strategies in the treatment of UTUC. Additionally, understanding the biological and genetic characteristics of UTUC that distinguish it from those of bladder cancer will also aid in establishing strategies for nephron-sparing.ope

Effect of prophylactic continuous infusion of isosorbide dinitrate on myocardial protection and hemodynamics in patients undergoing off-pump coronary bypass surgery.

BACKGROUND: Multi-vessel off-pump coronary bypass surgery (OPCAB) imposes cumulative myocardial ischemia/reperfusion injury, which may be attenuated by continuous infusion of nitrate. However, nitrate infusion and consequent decrease in preload may be hazardous during heart displacement which causes restrictive filling of the ventricles. Therefore, we evaluated the effect of nitrate infusion on myocardial protection and hemodynamics in patients undergoing OPCAB, in a prospective, randomized and controlled trial. METHODS: Fifty patients with stable angina and left ventricular ejection fraction >40% undergoing elective, isolated, multivessel OPCAB were enrolled. Patients were randomized equally to either continuous infusion of isosorbide dinitrate 0.5microg/kg/min or same amount of normal saline during the surgery. Operative data including hemodynamic variables, intraoperative ST segment changes and postoperative cardiac enzyme release (creatine kinase-MB, troponin T) were compared. RESULTS: Patients characteristic and operative data including ST segment changes and use of vasopressors were similar between the groups except the total amount of infused crystalloid during the surgery which was significantly higher in the nitrate group. Postoperative variables including cardiac enzyme release were also similar between the groups. CONCLUSIONS: Prophylactic continuous infusion of nitrate during OPCAB exerted no additional benefit in terms of myocardial protection. It also, was not associated with accentuated decrease in cardiac output during heart displacement, and the decrease in preload seems to have been nullified by modest increase in fluid therapy.ope

Heparin responsiveness during off-pump coronary artery bypass graft surgery: predictors and clinical implications

Aim:To evaluate the clinical impact of reduced heparin responsiveness (HR(reduced)) on the incidence of myocardial infarction (MI) following off-pump coronary artery bypass graft surgery (OPCAB), and to identify the predictors of HR(reduced).Methods:A total of 199 patients scheduled for elective OPCAB were prospectively enrolled. During anastomosis, 150 U/kg of heparin was injected to achieve an activated clotting time (ACT) of ≥ 300 s, and the heparin sensitivity index (HSI) was calculated. HSIs below 1.0 were considered reduced (HR(reduced)). The relationships between the HSI and postoperative MI, cardiac enzyme levels and preoperative risk factors of HR(reduced) were investigated.Results:There was no significant relationship between the HSI and cardiac enzyme levels after OPCAB. The incidence of MI after OPCAB was not higher in HR(reduced) patients. HR(reduced) occurred more frequently in patients with low plasma albumin concentrations and high platelet counts.Conclusion:HR(reduced) was not associated with adverse ischemic outcomes during the perioperative period in OPCAB patients, which seemed to be attributable to a tight prospective protocol for obtaining a target ACT regardless of the presence of HR(reduced).ope

Gene Expression Analysis of Aggressive Clinical T1 Stage Clear Cell Renal Cell Carcinoma for Identifying Potential Diagnostic and Prognostic Biomarkers

The molecular characteristics of early-stage clear cell renal cell carcinomas (ccRCCs) measuring ≤7 cm associated with poor clinical outcomes remain poorly understood. Here, we sought to validate genes associated with ccRCC progression and identify candidate genes to predict ccRCC aggressiveness. From among 1069 nephrectomies performed on patients, RNA sequencing was performed for 12 ccRCC patients with aggressive characteristics and matched pairs of 12 ccRCC patients without aggressive characteristics. Using a prospective cohort (ClinicalTrials.gov Identifier: NCT03694912), the expression levels of nine genes (PBRM1, BAP1, SETD2, KDM5C, FOXC2, CLIP4, AQP1, DDX11, and BAIAP2L1) were measured by reverse-transcription polymerase chain reaction from frozen tissues, and their relation to Fuhrman grade was investigated in 70 patients with small ccRCC (≤4 cm). In total, 251 genes were differentially expressed and presented fold changes with p-values < 0.05; moreover, 10 genes with the greatest upregulation or downregulation in aggressive ccRCC remained significant even after adjustment. We validated previously identified genes that were associated with ccRCC progression and identified new candidate genes that reflected the aggressiveness of ccRCC. Our study provides new insight into the tumor biology of ccRCC and will help stratify patients with early-stage ccRCC by molecular subtyping.ope

Digital Videoscopic Retrograde Intrarenal Surgeries for Renal Stones: Time-to-Maximal Stone Length Ratio Analysis

PURPOSE: To investigate 100 consecutive cases of videoscopic retrograde intrarenal surgery (RIRS) by a single surgeon and to evaluate factors associated with stone-free status and the learning curve thereof. MATERIALS AND METHODS: We analyzed the results of videoscopic RIRS in 100 patients who underwent primary treatment for renal stones from January 2015 to August 2016. Videoscopic RIRS were performed with URF-V and URF-V2 flexible video uteroscopes (Olympus) or a Flex-Xc flexible ureterorenoscope (KARL STORZ). Non-contrast computed tomography was taken at 3 months postoperatively to confirm the absence of stones. The stone characteristics included the location, maximal stone length (MSL), stone heterogeneity index (SHI), and mean stone density (MSD). Fragmentation efficacy was calculated as operative time (min) divided by removed MSL (mm), and was evaluated in the sequential order of operations. RESULTS: The mean age of the total patient was 60.0+/-14.0 years. The mean MSL was 13.1+/-6.2 mm. The average MSD was 734.2+/-327.6 Hounsfield unit (HU) and the SHI was 241.0+/-120.0 HU. The mean operation time was 65.1+/-45.7 min considering each renal unit. The stone-free rate at 3 months post-surgery was 87%. The estimated cut-off of the time-to-MSL ratio below 5 min/mm was 50. Multivariate analyses indicated a lower MSD [odds ratio (OR): 0.998; 95% confidence interval (CI): 0.996-0.999; p=0.047) and the last 50 cases (OR: 5.408, 95% CI: 1.337-30.426; p=0.030) as independent predictors of stone-free status after videoscopic RIRS. CONCLUSION: Low MSDs and the last 50 cases were significant predictors of stone-free rate in videoscopic RIRS.ope

Systemic Injection of Oncolytic Vaccinia Virus Suppresses Primary Tumor Growth and Lung Metastasis in Metastatic Renal Cell Carcinoma by Remodeling Tumor Microenvironment

Immune checkpoint inhibitors and tyrosine kinase inhibitors are the first-line treatment for metastatic renal cell carcinoma (mRCC), but their benefits are limited to specific patient subsets. Here, we aimed to evaluate the therapeutic efficacy of JX-594 (pexastimogene devacirepvec, Pexa-vec) monotherapy by systemic injection in comparison with sunitinib monotherapy in metastatic orthotopic RCC murine models. Two highly metastatic orthotopic RCC models were developed to compare the treatment efficacy in the International Metastatic RCC Database Consortium favorable-risk and intermediate- or poor-risk groups. JX-594 was systemically injected through the peritoneum, whereas sunitinib was orally administered. Post-treatment, tumor microenvironment (TME) remodeling was determined using immunofluorescence analysis. Systemic JX-594 monotherapy injection demonstrated therapeutic benefit in both early- and advanced-stage mRCC models. Sunitinib monotherapy significantly reduced the primary tumor burden and number of lung metastases in the early-stage, but not in the advanced-stage mRCC model. Systemic JX-594 delivery remodeled the primary TME and lung metastatic sites by increasing tumor-infiltrating CD4/8+ T cells and dendritic cells. Systemic JX-594 monotherapy demonstrated significantly better therapeutic outcomes compared with sunitinib monotherapy in both early- and advanced-stage mRCCs by converting cold tumors into hot tumors. Sunitinib monotherapy effectively suppressed primary tumor growth and lung metastasis in early-stage mRCC.ope

A Comparative Study of Laparoendoscopic Single-Site Surgery Versus Conventional Laparoscopy for Upper Urinary Tract Malignancies

PURPOSE: The proper indication for laparoendoscopic single-site surgery (LESS) in urology is still under debate, especially for malignant diseases. We compared the perioperative outcomes between LESS and conventional laparoscopy (CL) for upper urinary tract malignancies. MATERIALS AND METHODS: We reviewed the records of 75 patients who underwent radical nephrectomy, nephroureterectomy with bladder cuff excision, or partial nephrectomy with the LESS or CL approach between December 2008 and December 2010. We compared characteristics and perioperative outcomes between patients who underwent LESS or CL. All operations were performed by three surgeons using the transperitoneal approach. RESULTS: For all three surgery types, no differences in patient characteristics, estimated blood losses, transfusion rates, or durations of hospital stay were found between the two groups. No complications were found between the two groups in those who underwent nephroureterectomy with bladder cuff excision; however, significantly more complications were found in the LESS group than in the CL group in those who underwent radical nephrectomy or partial nephrectomy. Most of the complications with LESS radical nephrectomy occurred in the early introduction period of the technique. CONCLUSIONS: No significant differences in perioperative outcomes were found between the LESS and CL groups in those who underwent radical nephrectomy or nephroureterectomy with bladder cuff excision. Therefore, the use of LESS in these cases is expected to expand as surgeons gain more experience with this technique and as other technical advances in laparoscopic instruments occur. However, partial nephrectomy with LESS should be performed restrictively considering the current level of surgical skill.ope