• Biotechnology and Bioprocess Engineering:BBE
• /
• 제11권1호
• /
• pp.19-25
• /
• 2006

With particular regards to the hepatitis A virus (HAV), a terminal dry-heat treatment ($100^{\circ}C$ for 30 min) process, following lyophilization, was developed to improve the virus safety of a solvent/detergent-treated antihemophilic factor IX concentrate. The loss of factor IX activity during dry-heat treatment was of about 3%, as estimated by a clotting assay. No substantial changes were observed in the physical and biochemical characteristics of the dry-heat-treated factor IX compared with those of the factor IX before dry-heat treatment. The dry-heat-treated factor IX was stable for up to 24 months at $4^{\circ}C$, The dry-heat treatment after lyophilization was an effective process for inactivating viruses. The HAV and murine encephalomyocarditis virus (EMCV) were completely inactivated to below detectable levels within 10 min of the dry-heat treatment. Porcine parvovirus (PPV) and bovine herpes virus (BHV) were potentially sensitive to the treatment. The log reduction factors achieved during lyophilization and dry-heat treatment were ${\ge}5.60$ for HAV, ${\ge}6.08$ for EMCV, 2.64 for PPV, and 3.59 for BHV. These results indicate that dry-heat treatment improves the virus safety of factor IX concentrates, without destroying the activity. Moreover, the treatment represents an effective measure for the inactivation of non-lipid enveloped viruses, in particular HAV, which is resistant to solvent/detergent treatment.

• KSBB Journal
• /
• 제23권1호
• /
• pp.37-43
• /
• 2008

(주)녹십자는 1986년 "훽나인"을 B형 혈우병 치료제로 제조품목허가를 받아 B형 혈우병치료제 공급을 시작하였다. 또한 1991년 New York Blood Center에서 selvent/detergent 바이러스 불활화 방법을 도입하여 제조공정에 추가한 후 혈액유래 바이러스로부터 안전한 제품을 생산하여 왔다. 하지만 이 제품은 혈액응고 제2인자, 제7인자, 제10인자가 함유된 제9인자 복합체로, 정맥 혈전증과 파종성 혈관내응고병증 같은 혈전형성 부작용이 일어날 가능성이 있어, 훽나인보다 순도, 유효성, 바이러스 안전성이 우수한 제품의 개발이 필요하였다. 이를 위해 고순도 제9인자 제제인 "GreenNine VF" 제조공정을 개발하였다. GreenNine VF 제조공정은 기존의 훽나인 생산 공정에 heparin 친화성 크로마토그래피와 양이온 크로마토그래피가 추가된 공정으로, 바이러스 안전성을 증진시키기 위한 바이러스 필터 공정도 포함하고 있다. 이러한 공정에 의해서 산업적 규모로 생산된 GreenNine VF는 훽나인에 비해 순도와 바이러스 안전성이 월등히 높은 것으로 확인되었다. 또한 고순도 혈액응고 제9인자 제제인 Mononine, Octanyne, Berinin HS, Immunine STIM plus 600보다 순도가 더 높았다. Cryo-poor plasma 1,600 L를 원료로 사용했을 때 1 batch 당 250IU 분병제품 2,400병 이상, 500 IU 분병제품 1,200병 이상을 생산할 수 있었다.

• Journal of Microbiology and Biotechnology
• /
• 제18권7호
• /
• pp.1317-1325
• /
• 2008

Viral safety is an important prerequisite for clinical preparations of plasma-derived pharmaceuticals. One potential way to increase the safety of therapeutic biological products is the use of a virus-retentive filter. In order to increase the viral safety of human antihemophilic factor IX, particularly in regard to non-enveloped viruses, a virus removal process using a polyvinylidene fluoride membrane filter (Viresolve NFP) has been optimized. The most critical factor affecting the filtration efficiency was operating pH and the optimum pH was 6 or 7. Flow rate increased with increasing operating pressure and temperature. Recovery yield in the optimized production-scale process was 96%. No substantial changes were observed in the physical and biochemical characteristics of the filtered factor IX in comparison with those before filtration. A 47-mm disk membrane filter was used to simulate the process performance of the production-scale cartridges and to test if it could remove several experimental model viruses for human pathogenic viruses, including human hepatitis A virus (HAV), porcine parvovirus (PPV), murine encephalomyocarditis virus (EMCV), human immunodeficiency virus type 1 (HIV), bovine viral diarrhea virus (BVDV), and bovine herpes virus (BHV). Non-enveloped viruses (HAV, PPV, and EMCV) as well as enveloped viruses (HIV, BVDV, and BHV) were completely removed during filtration. The log reduction factors achieved were $\geq$6.12 for HAV, $\geq$4.28 for PPV, $\geq$5.33 for EMCV, $\geq$5.51 for HIV, $\geq$5.17 for BVDV, and $\geq$5.75 for BHV. These results indicate that the virus filtration process successfully improved the viral safety of factor IX.

• 대한임상검사과학회지
• /
• 제47권4호
• /
• pp.237-242
• /
• 2015

aPTT 참고치의 정상범위 내에서 하한 측 10% (29.1~30.9 sec)와 상한 측 10% (38.0~41.9 sec)에 포함된 정상성인의 혈액응고인자 활성도를 분석하여 하한 측과 상한 측간에 혈액응고인자의 종류와 각각의 활성도가 성별, 연령 및 ABO 혈액형 등에 통계학적으로 유의한 차이를 보이는지 알아보고자 하였다. 성별에 따른 혈액응고인자들의 활성도 차이를 분석한 결과 하한 측에서 IX (p=0.0088)만 남성이 여성보다 높았으며, 상한 측에서 IX (p<0.0001)와 X (p=0.0013)은 남성이 여성보다 높았다. 연령군간 혈액응고인자들의 활성도 차이 검정은 하한 측에서 VIII (p<0.0001), IX (p=0.0050)는 60세 이상이 60세 미만보다 높았으며, XII (p=0.0285)는 60세 이상보다 60세 미만이 높았다. 상한 측에서 V (p=0.0219), VIII (p=0.0005), IX (p=0.0014)는 60세 이상이 60세 미만보다 높았다. O형과 non-O형의 혈액형 구분에 의한 혈액응고인자들의 활성도 차이는 VIII (p<0.001)은 양쪽 그룹에서 non-O형이 O형보다 높았으며, XII (p=0.016)는 상한 측에서 non-O형이 O형보다 낮았다.

• Journal of Genetic Medicine
• /
• 제13권2호
• /
• pp.89-94
• /
• 2016

Purpose: Molecular genetic analysis is the main approach used for prenatal diagnosis of hemophilia A and B. However, in certain cases, such analysis is uninformative. In such situations, direct measurement of fetal coagulation factor levels is still the best option, and it may be the only option in some cases. This study was conducted to determine the normal ranges of mid-trimester cord blood factor VIII (FVIII) and IX (FIX) in a Korean population. Materials and Methods: Twenty-six FVIII samples and 29 FIX samples were assayed in fetal cord blood acquired by ultrasound-guided cordocentesis. Sampling was conducted during gestational ages of 19-24 weeks. Results: The mean and standard deviations for FVIII and FIX activity were $45.5{\pm}30.5%$ and $19.9{\pm}12.2%$, respectively. Ranges for FVIII and FIX were 1.5-125.0% and 6.0-52.0%, respectively. Conclusion: Our study revealed the normal ranges and lowest level of factor VIII and factor IX in non-affected normal fetus by fetal cord blood sampling during the mid-trimester in a Korea population. The factor assay of the fetal cord blood is invasive but feasible and provides important basic data related to hemophilia.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권20호
• /
• pp.8923-8929
• /
• 2014

Background: Increasing evidence suggests that stromal monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX) may play key roles in tumor development. However, their clinical value remains largely unexplored in gastric cancer (GC). The present study aimed to determine clinicopathological significance and prognostic values of stromal MCT4 and CA IX in GC. Materials and Methods: Specimens from 143 GC patients were immunohistochemically stained using polyclonal anti-MCT4 and anti-CA IX antibodies. Expression was correlated with patient clinicopathologic characteristics and survival data. Results: High stromal MCT4 expression was detected in 72 of 143 (50.3%) GCs and high CA IX in 74 (51.7%). Both high stromal MCT4 and CA IX were correlated with advanced TNM stage (p=0.000; p=0.000). High CA IX expression was positively related to depth of invasion (p=0.022) and positive lymph nodes (p=0.002) as well. Survival analysis indicated high expression of stromal MCT4 to be an independent factor in predicting poor overall survival (OS) (HR and 95%CI=1.962, 1.032-3.729, p=0.040) and disease free survival (DFS) (HR and 95%CI=2.081, 1.158-3.741, p=0.014) of GC patients. However, high CA IX expression exhibited no significant predictive value. Conclusions: These findings suggest that high expression of stromal MCT4 and CA IX proteins is significantly correlated with GC progression. High stromal MCT4 heralds worse outcome of GC patient, suggesting a novel candidate prognostic marker and therapeutic target.

• Archives of Plastic Surgery
• /
• 제39권2호
• /
• pp.150-153
• /
• 2012

Hemophilia B is a rare blood coagulation disorder. Complications such as bleeding and hematoma can cause necrosis of flaps, wound disruption, and the disturbance of wound healing. In particular, guidelines for flap operations in hemophilia B patients have still not been defined, and case reports are rare. We reconstructed the heel of a 41-year-old male hemophilia B patient using a reverse sural artery flap operation. The patient presented with mild hemophilia, having 27% of the normal value of coagulation factor IX. Coagulation and the changing value of the coagulation factor were regularly measured, and 70% of the normal value of coagulation factor IX was maintained through the injection of recombinant coagulation factors and antihemorrhagics. Hematoma developed twice (postoperative day [POD] 5 and POD 7) and in each case the hematoma was removed. Injections of recombinant coagulation factors and antihemorrhagics were continuously administered until postoperative week 2. When the coagulation factors were within normal ranges. In this article, a hemophilia B patient underwent reverse sural artery flap surgery and the healing progress was analyzed. We conclude that higher than baseline levels of coagulation factors are needed for successful healing in reverse sural artery flap surgery.

• Nuclear Engineering and Technology
• /
• 제55권2호
• /
• pp.640-647
• /
• 2023

Material corrosion in nuclear power plant (NPP) is not controlled only by amine injection but also by ion exchange (IX) which is the best option to remove trace Na⁺. This study was conducted to understand the Na⁺ leakage characteristics of IX beds packed with ethanolamine-form (ETAH-form) and hydrogen-form (H-form) resins in the simulated water-steam cycle in terms of intrinsic behaviors of four kinds of cation-exchange resins through ASTM test and Vanselow mass action modeling. Na⁺ was inappreciably escaped throughout the channel created in resin layer. Na⁺ leakage from IX bed was non-linearly raised because of its decreasing selectivity with increasing Na⁺ capture and with increasing the fraction of ETAH-form resin. Na⁺ did not reach the breakthrough earlier than ETAH⁺ and NH₄⁺ due to the increased selectivity of Na⁺ to the cation-exchange resin (H⁺ < ETAH⁺ < NH₄⁺ ≪ Na⁺) at the feed composition. Na⁺ leakage from the resin bed filled with small particles was decreased due to the enhanced dynamic IX processes, regardless of its low selectivity. Thus, the particle size is a predominant factor among intrinsic properties of IX resin to reduce Na⁺ leakage from the condensate polishing plant (CPP) in NPPs.

• 한국동물위생학회지
• /
• 제34권2호
• /
• pp.191-193
• /
• 2011

A 3-month-old intact male, Labrador retriever was presented with the history of coagulopathy and anemia. The results of initial screening tests of the hemostatic system yielded a tentative diagnosis of hemophilia. Activated partial thromboplastin time (APTT) was distinctly prolonged (106 seconds) and prothrombin time (PT) was not detected due to markedly prolonged test time. Whole blood transfusions (20 me l/kg body weight) were carried out prior to assays of coagulation factor. After transfusion, the patient recovered well and hemorrhage ceased. Blood samples were assessed for coagulation factor activity. The patient showed markedly low factor IX coagulation activity (5%, reference range: 7~140%) and was diagnosed with hemophilia B. After recovery, the patient was discharged from the hospital. However, 4 months later the patient was re-hospitalized for recurrence of the initial symptoms. The owner did not want to pursue further treatment and the patient died of respiratory distress two days later.

• 전력전자학회논문지
• /
• 제4권6호
• /
• pp.539-546
• /
• 1999

본 논문에서는 역률개선용 단일 수위치 부수투 플라이백 결합형 ZCS 준공진 컨버터(quasi-resonant converter(QRC))를 제안한다. 제안된 컨버터는 입력전류를 불연속 모드로 동작과 zero-crossing-point에서의 왜곡을 개선함으로써 고조파를 감소시켜 역률을 향상시켰으며 좋은 출력전압의 레귤레이션 성능을 가지고 있다. 또한 능동 클램프회로를 제안된 회로의 동작특성에 맞게 스위칭 시간을 조절해 줌으로써 ZCS-QR의 일잔적인 특성인 스위치 차단시의 스위치 양단전압의 공진현상을 제거하여 스위치의 전압스트레스를 줄였다. 체계적인 설계를 위하여 설계식을 제안하였으며 제안된 설계식을 통하여 프로토타입 컨버터를 설계하였다. 실험결과 효율은 약 87%, 역률은 약0.985이상을 얻었다. 따라서 본 컨버터는 스위칭 주파수가 수백kHz이상이고 높은 레귤레이션 성능을 요구하는 낮은 전압의 소용량 컨버터에 적합하다.