• Journal of Pharmaceutical Investigation
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• 제39권4호
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• pp.263-267
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• 2009

The purpose of this study is to evaluate the efficacy of stipulated cleaning process, and the prohibition of cross-contamination and microbiological contamination, which inadequate cleaning in multi-production could occur, through cleaning validation of multi-purpose facility used to produce five biopharmaceutical products as sterile injection. After production of five biopharmaceutical products such as hGH, rhGCSF, rhEPO, rhFSH and rhIFN using vial filling machine, the cleaning validation such as residual analysis of active ingredients or human serum albumin, measurement of total organic carbon (TOC), residual analysis of detergent and microbiological contamination were carried out. In the case of rhGH and rhGCSF clean validations, drug residues were not detected. Furthermore, in the case of rhEPO, rhFSH and rhIFN clean validations, human serum albumin residues were not detected. At TOC (total organic carbon) analysis, all clean validations gave the TOC of about average 137.93%, not more than 150% of acceptance criteria. At sodium analysis for the checking of residues of cleaning agent, sodium residues were not detected. In sterility test, they showed no microbiological contamination of bacteria and fungi. Thus, this cleaning validation was determined as successful in protection of cross-contamination and induction of safety in multi-purpose facility.

• Bulletin of the Korean Chemical Society
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• 제28권5호
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• pp.730-736
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• 2007

The interaction of a polyoxometal (POM), K6SiW11Co(H2O)O39.10H2O (K6) as a Keggin, with human serum albumin (HSA) was studied by different methods and techniques. Binding studies show two sets of binding sites for interaction of POM to HSA. Binding analysis and isothermal calorimetery revealed that, the first set of binding site has lower number of bound ligand per mole of protein (ν), lower Hill constant (n), higher binding constant (K), more negative entropy (ΔS) and more electrostatic interaction in comparison to the second set of binding site. In addition, differential scanning calorimetery (DSC) and spectrophotometery data showed that, there are two energetic domains. The first domain is less stable (lower Tm and Cp) which corresponds to the tail segment of HSA and another with more stability is related to the head segment of HSA. Polyoxometal also decreases the stability of protein as Tm, secondary and tertiary structure as well as quenching of the fluorescence decrease. On other hand, perturbations in tertiary structure are more than secondary structure.

• 대한방사성의약품학회지
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• 제1권2호
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• pp.104-108
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• 2015

Human serum albumin (HSA) has potential for diagnosis and therapy in clinical setting. The purpose of experiments was to develop and evaluate $^{68}Ga$-HSA as a PET agent for diagnosis of acute inflammation. NOTA-HSA was synthesized by conjugating 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid to HSA in 0.1 M sodium carbonate buffer (pH 9.5) and then purified using a PD-10 size-exclusion column. NOTA-HSA was labeled with $^{68}Ga$ at room temperature for 10 min, and 8.4% sodium hydrogen carbonate buffer was added for neutralization. $^{68}Ga$-NOTA-HSA was purified using alumina N plus light cartridge and $0.22{\mu}m$ syringe filter. Labeling efficiency and radiochemical purity were determined by ITLC-SG with 0.1 M citric acid. Biodistribution study was performed in a male BALB/c mice model of Carrageenan-induced acute inflammation. Animal PET study was performed in acute inflammation mice model after tail vein injection of $^{68}Ga$-HSA. This radiotracer showed high labeling efficiency (>99%) around pH 7. Biodistribution study showed higher inflamed footpad uptake than control footpad uptake. Animal PET study revealed 2 times higher uptake on inflamed footpad compared to control footpad. In these experiments, we developed $^{68}Ga$-HSA for acute inflammation PET imaging and evaluated it in a mouse disease model. The results demonstrated that $^{68}Ga$-HSA has potential as a PET imaging agent for diagnosis of acute inflammation.

• 대한핵의학회지
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• 제27권1호
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• pp.88-97
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• 1993

Anterior abdominal scintigraphy after intravenous injection of $^{99m}Tc$-human serum albumin ($^{99m}Tc$-HSA 20 mCi) was done in 16 patients with connective tissue diseases and 15 healthy control patients. Patients with proteinuria or hepatopathy were excluded. 1) 7 (44%) patients among 16 connective tissue disease patients without the apparent evidence of external protein loss showed abnormal intestinal accumulation of albumin. 6 patients with positive albumin scintigraphy showed bypoalbuminemia. 2) There was no false positive scintigraphic finding in control group. 3) The serum albumin level in connective tissue disease patients ($3.1{\pm}0.6 g/dl$, n=16) was lower than control patients ($3.9{\pm}0.3 g/dl$, n=15) (p<0.0001). 4) The serum albumin level was lower in connective tissue disease patients with positive $^{99m}Tc$-HSA scan ($2.8{\pm}0.6 g/dl$, n=7) than the connective tissue disease patients with negative scan ($3.3{\pm}0.3 g/dl$, n=9) (p<0.05). 5) The hemoglobin level in connective tissue disease patients with positive nan ($10.6{\pm}2.91 g/dl$) was lower than that of the control group ($13.6{\pm}1.5 g/dl$) (p<0.05). Mypoalbuminemia is frequently involved in chronic connective tissue diseases. Protein losing enteropathy (PLE) is also responsible for the majority of the bypoalbuminemia in these patients. But it has been ignored because the conventional method for the diagnosis of PLE was difficult to perform. $^{99m}Tc$-HSA scan also must be validated by more extended study and comparison with the quantitative study such as stool ${\alpha}-1$ antitrypsin measurement. There must be a reevaluation of PLE in various diseases especially in connective tissue diseases with easy, fast, economical, and non-invasive method.

• Clinical and Experimental Reproductive Medicine
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• 제22권2호
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• pp.171-181
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• 1995

Ovarian hyperstimulation syndrome(OHSS) is one of the well-known complication of controlled ovarian hyperstimulation(COH). Though there have been numerous measures to prevent the occurrence of OHS, it has not been completely preventable until now. The fluid shift from the intravascular space to the third space is due to decreased oncotic pressure of the serum. The objective of this study was to evaluate if IV administration of 20% albumin in those patients with OHSS risk can make prevention of severe OHSS. We retrospectively analysed 70 patients undergoing IVF-ET who had serum peak estradiol($E_2$) level of >2,500 pg/ml and/or the number of oocytes retrieved over 20. The treatment group(n=39) received albumin while the control group(n=31) did not. After 40 grams of human albumin diluted in 1,000 ml of 0.9% sodium chloride solution, the treatment group received half of the fluid during oocyte retrieval, the remainder in the recovery suite. The results were as follows; There were significant differences in the levels of serum peak $E_2$ and number of oocytes retrieved between the two groups(p<0.05). However, there were no significant differences in the incidence of OHSS and pregnancy rate or multifetal pregnancy rate. In conclusion, administration of albumin to OHSS risk patients did not reduce the rate of OHSS in IVF-ET. However, if we consider the fact that there were differences in the level of peak serum $E_2$ and oocyte numbers, further prospective study may be needed.

• Journal of the Optical Society of Korea
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• 제7권4호
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• pp.240-244
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• 2003

Simultaneous determination of concentrations for four major components in human blood serum was investigated using a Fourier-transform mid-infrared spectroscopy. Infrared spectra of human blood serum were measured in 8.404 ∼ 10.25 ${\mu}m$ range where the highest absorption peaks of glucose are located. A partial least square (PLS) algorithm was utilized to establish a calibration model for determining total protein, albumin, globulin and glucose levels which are commonly measured metabolites. The standard error of cross validation obtained from our multivariate calibration model was 0.24 g/dL for total protein, 0.15 g/dL for albumin, 0.17 g/dL for globulin, and 6.68 mg/dL for glucose, which are comparable with or meet the criteria for clinical use. The results indicate that the infrared absorption spectroscopy can be used to predict the concentrations of clinically important metabolites without going through a chemical process with a reagent.

• BMB Reports
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• 제43권11호
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• pp.766-771
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• 2010

The biological evaluation of a new synthesized Pt(II)-complex, 2,2'-bipyridin Butylglycinato Pt(II) nitrate, an anti-tumor component, was studied at different temperatures by fluorescence and far UV circular dichroism (CD) spectroscopic methods. Human serum albumin (HSA) and human tumor cell line K562 were as targets. The Pt(II)-complex has a strong ability to quench the intrinsic fluorescence of HSA. Binding and thermodynamic parameters of the interaction were calculated by fluorescence quenching method. Far-UV-CD results showed that Pt(II)-complex induced increasing in content of $\alpha$ helical structure of the protein and stabilized it. The 50% cytotoxic concentration ($Cc_{50}$) of complex was determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay at different incubation times. Also, fluorescence staining with DAPI (4,6-diamidino-2-phenylindole) revealed some typical nuclear changes, which are characteristic of apoptosis. Above results suggest that Pt (II) complex is a promising anti-proliferative agent and should execute its biological effects by inducing apoptosis.

• Journal of Chest Surgery
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• 제24권11호
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• pp.1058-1067
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• 1991

High potassium cardioplegia is a widely accepted procedure to enhance myocardial protection from ischemic injuries associated with open heart surgery. Maintaining optimum osmolarity of the cardioplegic solution is one of the required conditions for an ideal cardioplegic solution Albumin is an frequently added component for maintaining optimum osmolarity of clinically used cardioplegic solutions. But the source of albumin is human blood so that the supply is limited and the cost of manufacturing is relatively high. Recently there are moves to minimized the use of blood product for fear of blood-associated infections or immunological disorders. In this experiment, we substituted mannitol or glucose for albumin added to the cardioplegic solution which has been used at the Wonju Medical College, To determine whether addition of mannitol or glucose instead of albumin in the cardioplegic solution can produce satisfactory myocardial protection during ischemia, three different groups of isolated rat heart perfused by modified Langendorff technique were studied. Wonju Cardioplegic Solution was selected as a standard high potassium[18mEq/L of K+] cardioplegic solution. Three kinds of cardioplegic solution were made by modifying the composition maintaining the same osmolarity[339$\pm$1mOsm/Kg] Isolated rat heart were perfused initially with retrograde nonworking mode and then changed to working mode. After measuring the heart rate, systolic aortic pressure, aortic flow, coronary flow, ischemic arrest by aorta cross clamp and cardioplegia was made maintaining the temperature of water jacket at 10oC. The heart was rewarmed and reperfused after 60min of ischemic arrest with intermittent cardioplegia at the 30min interval. The time to return of heart beat and the time required to get. Regular heart beat were observed after reperfusion. The recovery rate of the functional variables-heart rate, systolic aortic pressure, aortic flow, coronary flow and cardiac output were calculated and compared among the three groups of different cardioplegia-albumin, mannitol, and glucose. The wet weight and dry weight was measured and the water content of the heart as figured out for comparison. The time to return of heart beat was fastest in the albumin group, The functional recovery rates were best in the albumin group also. In the above conditions, albumin was the best additive to the cardioplegic solution compared to the mannitol or glucose.

• Childhood Kidney Diseases
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• 제4권2호
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• pp.102-110
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• 2000

목 적 : 고농도 인알부민은 신증후군성 부종의 치료에 효과적으로 사용되어 왔으나 고혈압, 심부전등의 위험이 있고 알부민 투여에 따른 고단백 부하가 병적인 사구체 상피세포의 손상을 가중시켜 신증후군의 임상적 경과에 나쁜 영향을 끼칠 수 있는 것으로 보고되었다. 이에 저자들은 신증후군 환아에서 인알부민 투여가 신증후군의 임상 결과에 미치는 영향을 관찰하기 위하여 전향적인 연구를 시행하였다. 방 법 : 1997년 3월부터 1999년 9월까지 이화의대 부속 목동병원 소아과에 신증후군으로 입원한 환아중 신조직 검사상 미세변화형이었으나 재발하였거나 임상적으로 미세변화형에 합당하였던 환아에게 무작위로 20$\%$ 알부민 1 g/kg과 furosemide 2 mg/kg를 1-3일간 정맥 투여하였다. 이중 표준 스테로이드 치료(prednisolone 2 mg/kg 또는 calcort-한독약품 2.4 mg/kg)에 8주 내에 반응을 보이고 1년 이상 추적 관찰이 가능했던 스테로이드 반응성 신증후군 환아 26명 (알부민 투여군 13명, 대조군 13명)을 대상으로 임상경과를 비교하였다. 결 과 : 1) 완전 관해까지의 스테로이드 치료기간은 알부민 투여군에서 $13.7{\pm}6.4$일의 대조군의 $7.5{\pm}2.8$일보다 유의하게 길었다 (P<0.05). 2) 첫 재발까지의 기간은 알부민 투여군에서 $94{\pm}63.5$일로 대조군의 $190{\pm}106.4$일에 비하여 유의하게 짧았다 (P<0.05). 완전 관해후 1년내 재발율은 알부민 투여군에서 77$\%$ (10/13)로 대조군의 46$\%$(6/13)보다 높았으나 두군간에 유의한 차이는 없었다 (P>0.05). 완전 관해후 1년간 재발 횟수는 알부민 투여군이 $1.9{\pm}0.8$회로 대조군의 $1.5{\pm}0.5$회와 유의한 차이는 없었다 (P>0.05). 3) 일회뇨단백/크레아티닌 비는 알부민 투여군에서 투여 후 2, 4일에 유의하게 증가하였다 (P<0.05). 4) 일일체중감소, 혈압, 혈청 Na, K 농도의 변화에는 두 군간에 유의한 차이가 없었다 (P>0.05). 결 론 : 스테로이드 반응성 신증후군에서 인알부민 투여는 스테로이드에 대한 반응을 지연시키고 첫 재발까지의 기간을 단축시키는등 임상결과를 악화시킬 수도 있으므로 알부민 투여에 신중을 기하여야 할 것으로 생각된다.

• 한국수정란이식학회:학술대회논문집
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• 한국수정란이식학회 2006년도 The 6th Intermational Symposium on Developmental Biotechnology
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• pp.76-77
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• 2006