• 제목/요약/키워드: Multiple-dose

검색결과 487건 처리시간 0.022초

Rapid Selection of Multiple Gene Integrant for the Production of Recombinant Hirudin in Hansenula polymorpha

  • Kim Hwa Young;Sohn Jung Hoon;Kim Chul Ho;Rao K. Jagannadha;Choi Eui Sung;Kim Myung Kuk;Rhee Sang Ki
    • Biotechnology and Bioprocess Engineering:BBE
    • /
    • 제5권1호
    • /
    • pp.1-6
    • /
    • 2000
  • For the rapid selection of higher recombinant hirudin producing strain in a methylotrophic yeast Hansenula polymorpha, a multiple gene integration and dose-dependent selection vector, based on a telomere-associated ARS and a bacterial aminoglycoside 3-phosphotransferase (aph) gene, was adopted. Two hirudin expression cassettes (HV1 and HV2) were constructed using the MOX promoter of H. polymorpha and the mating factor $\alpha$ secretion signal of S. cerevisiae. Multiple integrants of a transforming vector containing hirudin expression cassettes were easily selected by using an antibiotic, G418. Hirudin expression level and integrated plasmid copy number of the tested transformants increased with increasing the concentration of G418 used for selection. The expression level of HV1 was consistently higher than that of HV2 under the similar conditions, suggesting that the gene context might be quite important for the high-level gene expression in H. polymorpha. The highest hirudin producing strain selected in this study produced over 96 mg/L of biologically active hirudin in a 500-mL flask and 165 mg/L in a 5-L fermentor.

  • PDF

청간소요산합인진위령탕의 Alcoholism에서의 간손상회복 및 학습능력향상 효과 (Effects of the Cheonggansoyo-san added Injinwiryeong-tang on Recovery from Damaged-liver and Mental-faculty Improvement in Alcoholism)

  • 임종필;박영서;김훈
    • 동의생리병리학회지
    • /
    • 제18권2호
    • /
    • pp.571-574
    • /
    • 2004
  • Effects of the Cheonggansoyo-san added Injinwiryeong-tang on recovery from damaged-liver and mental-faculty improvement in alcoholism were studied using male Sprague-Dawley rats, The rats were assigned into 4 groups; normal, control and CIX group. Control group administered ethanol(25 v/v %) at a dose 3 g/kg, while CIX group administered the water extract of Cheonggansoyo-san added Injinwiryeong-tang (CIX) 30 min before treating same dose of ethanol as control group for 10 days, orally. The GOT and GPT activities of rats were checked by Reitman & Frankel method, and all groups were subjected to trials of straight channel on the 1 st day and to those of multiple T-maze during the following 3 days. The GOT and GPT activities were increased in control group, but decreased in CIX group significantly. The time required in normal group for the straight channel of the 2nd and 3rd trials was significantly shorter than that of the 1 st, while the control group showed no significance. In the time required for the multiple T-maze trials, the control group showed no significance. But in the straight or T-maze trials, the CIX group showed significant decrease in the time required against the control group.

Accumulated Mannitol and Aggravated Cerebral Edema in a Rat Model of Middle Cerebral Artery Infarction

  • Cho, Jae-Man;Kim, Yeon-Hee;Han, Hyung-Soo;Park, Jae-Chan
    • Journal of Korean Neurosurgical Society
    • /
    • 제42권4호
    • /
    • pp.337-341
    • /
    • 2007
  • Objective : Repeated administration of mannitol in the setting of large hemispheric infarction is a controversial and poorly defined therapeutic intervention. This study was performed to examine the effects of multiple-dose mannitol on a brain edema after large hemispheric infarction. Methods : A middle cerebral artery was occluded with the rat suture model for 6 hours and reperfused in 22 rats. The rats were randomly assigned to either control (n=10) or the mannitol-treated group (n=12) in which intravenous mannitol infusions (0.8 g/kg) were performed six times every four hours. After staining a brain slice with 2,3,5-triphenyltetrazolium chloride, the weight of hemispheres, infarcted (IH) and contralateral (CH), and the IH/CH weight ratio were examined, and then hemispheric accumulation of mannitol was photometrically evaluated based on formation of NADH catalyzed by mannitol dehydrogenase. Results : Mannitol administration produced changes in body weight of $-7.6{\pm}1.1%$, increased plasma osmolality to $312{\pm}8\;mOsm/L$. It remarkably increased weight of IH ($0.77{\pm}0.06\;gm$ versus $0.68{\pm}0.03\;gm$ : p<0.01) and the IH/CH weight ratio ($1.23{\pm}0.07$ versus $1.12{\pm}0.05$ : p<0.01). The photometric absorption at 340 nm of the cerebral tissue in the mannitol-treated group was increased to $0.375{\pm}0.071$ and $0.239{\pm}0.051$ in the IH and CH, respectively from $0.167{\pm}0.082$ and $0.162{\pm}0.091$ in the IH and CH of the control group (p<0.01). Conclusion : Multiple-dose mannitol is likely to aggravate cerebral edema due to parenchymal accumulation of mannitol in the infarcted brain tissue.

홍삼.가시오가피.동충하초 혼합수엑스의 항당뇨작용 (Anti-diabetic Effects of Mixed Water Extract from Ginseng Radix Rubra, Acanthopanacis Cortex, and Cordyceps)

  • 고성권;김재수;최용의;이승정;박경수;정성현
    • 생약학회지
    • /
    • 제33권4호통권131호
    • /
    • pp.337-342
    • /
    • 2002
  • The effect of water extract composed of panax ginseng radix rubra, acanthopanacis cortex, and cordyceps (PAC) on diabetic animal models were investigated in two different diabetic animal models. FAC water extract significantly reduced the plasma glucose levels on day 30 as compared with the diabetic control group in $KKA^Y$ obese, hyperglycemic and hyperglycemic and hyperinsulinemic mice, and also reduced the plasma glucose levels as well as total cholesterol in multiple low dose (MLD) strep tozotocin-induced diabetic SD rats. PAC water extract also showed an inhibitory effect on reduction of body weight and on development of MLD STZ-induced diabetic state. Elevated kidney hypertrophy, which is a characteristic feature shown in early stage of diabetic nephropathy and calculated as the ratio of kidney mass (g) relative to the body weight (g), was also markedly improved in PAC water extract- treated group as compared to the diabetic control group. Taken together, these data suggest that PAC water extract may have a potential as a antidiabetic agent in type 2 diabetes mellitus.

Radiotherapy Alone is Associated with Improved Outcomes Over Surgery in the Management of Solitary Plasmacytoma

  • Li, Qi-Wen;Niu, Shao-Qing;Wang, Han-Yu;Wen, Ge;Li, Yi-Yang;Xia, Yun-Fei;Zhang, Yu-Jing
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제16권9호
    • /
    • pp.3741-3745
    • /
    • 2015
  • Background: A moderate dose of radiation is the recommended treatment for solitary plasmacytoma (SP), but there is controversy over the role of surgery. Our study aimed at comparing different treatment modalities in the management of SP. Materials and Methods: Data from 38 consecutive patients with solitary plasmacytoma, including 16 with bone plasmacytoma and 22 with extramedullary plasmacytoma, were retrospectively reviewed. 15 patients received radiotherapy alone; 11 received surgery alone, and 12 received both. The median radiation dose was 50Gy. All operations were performed as radical resections. Local progression-free survival (LPFS), multiple myeloma-free survival (MMFS), progression-free survival (PFS) and overall survival (OS) were calculated and outcomes of different therapies were compared. Results: The median follow-up time was 55 months. 5-year LPFS, MMFS, PFS and OS were 87.0%, 80.9%, 69.8% and 87.4%, respectively. Univariate analysis revealed, compared with surgery alone, radiotherapy alone was associated with significantly higher 5-year LPFS (100% vs 69.3%, p=0.016), MMFS (100% vs 51.4%, p=0.006), PFS (100% vs 33.7%, p=0.0004) and OS (100% vs 70%, p=0.041). Conclusions: Radiotherapy alone can be considered as a more effective treatment for SP over surgery. Whether a combination of radiotherapy and surgery improves outcomes requires further study.

Streptozotocin 유도 당뇨병에 대한 위령선(威靈仙) 추출물의 방어 효과 (Protective Effect of Radix Clematidis Extract on Streptozotocin-induced Diabetes)

  • 함경완;김은경;송미영;권강범;송제호;서은아;류도곤
    • 동의생리병리학회지
    • /
    • 제22권3호
    • /
    • pp.580-584
    • /
    • 2008
  • In the present study, Radix clematidis extract (RCE) was evaluated to determine if it could protect pancreatic ${\beta}$ cells against multiple low dose streptozotocin (MLDS)-induced diabetes. Injection of mice with MLDS resulted in hyperglycemia and hypoinsulinemia, which was confirmed by immunohistochemical staining. However, the induction of diabetes by MLDS was completely prevented when mice were pre-administrated with RCE. Generation of oxidative stress is implicated in MLDS, a ${\beta}$ cell specific toxin-induced islet cell death. In this context, to elucidate the mechanisms of protective effects in RCE pre-administrated diabetic mice, we investigated the expression of heme oxygenase-1 (HO-1), which is one of the anti-oxidant enzymes. MLDS-induced HO-1 expressions were significantly reduced in MLDS-treated mice. However, the decrease of HO-1 by MLDS were protected by pretreatment of RCE. The molecular mechanism by which RCE inhibits diabetic conditions by MLDS appears to involve inhibition of HO-1 expression. Taken together, these results reveal the possible therapeutic value of RCE for the prevention of type 1 diabetes progression.

Tolerability and pharmacokinetics of ginsenosides Rb1, Rb2, Rc, Rd, and compound K after single or multiple administration of red ginseng extract in human beings

  • Choi, Min-Koo;Jin, Sojeong;Jeon, Ji-Hyeon;Kang, Woo Youl;Seong, Sook Jin;Yoon, Young-Ran;Han, Yong-Hae;Song, Im-Sook
    • Journal of Ginseng Research
    • /
    • 제44권2호
    • /
    • pp.229-237
    • /
    • 2020
  • Background: We investigated the tolerability and pharmacokinetic properties of various ginsenosides, including Rb1, Rb2, Rc, Rd, and compound K, after single or multiple administrations of red ginseng extract in human beings. Methods: Red ginseng extract (dried ginseng > 60%) was administered once and repeatedly for 15 days to 15 healthy Korean people. After single and repeated administration of red ginsengextract, blood sample collection, measurement of blood pressure and body temperature, and routine laboratory test were conducted over 48-h test periods. Results: Repeated administration of high-dose red ginseng for 15 days was well tolerated and did not produce significant changes in body temperature or blood pressure. The plasma concentrations of Rb1, Rb2, and Rc were stable and showed similar area under the plasma concentration-time curve (AUC) values after 15 days of repeated administration. Their AUC values after repeated administration of red ginseng extract for 15 days accumulated 4.5- to 6.7-fold compared with single-dose AUC. However, the plasma concentrations of Rd and compound K showed large interindividual variations but correlated well between AUC of Rd and compound K. Compound K did not accumulate after 15 days of repeated administration of red ginseng extract. Conclusion: A good correlation between the AUC values of Rd and compound K might be the result of intestinal biotransformation of Rb1, Rb2, and Rc to Rd and subsequently to compound K, rather than the intestinal permeability of these ginsenosides. A strategy to increase biotransformation or reduce metabolic intersubject variability may increase the plasma concentrations of Rd and compound K.

Utilization of Preventive Therapy in Korean Migraine Patients

  • Kim, Yewon;Park, Susin;Kim, Eonjeong;Je, Nam Kyung
    • 한국임상약학회지
    • /
    • 제31권1호
    • /
    • pp.35-43
    • /
    • 2021
  • Background: Migraine is a common neurological disorder that affects the quality of life and causes several health problems. Preventive migraine treatment can reduce migraine frequency, headache severity, and health care costs. This study aimed to estimate the utilization of migraine preventive therapy and associated factors in eligible patients. Methods: We studied 534 patients with migraine who were eligible for migraine preventive therapy using 2017 National Patient Sample (NPS) data from the Health Insurance Review and Assessment Service (HIRA). We estimated the migraine days by calculating the monthly average number of defined daily dose (DDD) of migraine-specific acute drug. Patients with a monthly average number of DDD of 4 or more were considered as subjects for preventive treatment. Chi-square test and multiple logistic regression analysis were used to determine the association between the preventive therapy and the influencing variables. Results: Less than half of the eligible patients for prophylaxis (n=234, 43.8%) were prescribed preventive therapy. Multiple logistic regression results show that migraine preventive therapy was influenced by age, the type of migraine, and some comorbidities. Patients over the age of 50 tend to receive less prophylactic treatment than under the age of 40. On the other hand, migraine patients with epilepsy or depression were more likely to receive preventive therapy. Sumatriptan was the most preferred medication for acute treatment, and propranolol was the most commonly prescribed drug for prevention. Conclusions: More than half of the patients who were candidates for migraine prophylaxis were not receiving suitable preventive treatment. Positive factors affecting the use of migraine prevention were the presence of comorbidities such as epilepsy and depression.

양성자 선량 분포 검증을 위한 즉발감마선 분포측정 장치 최적화 연구 (Study on Optimization of Detection System of Prompt Gamma Distribution for Proton Dose Verification)

  • 이한림;민철희;박종훈;김성훈;김찬형
    • 한국의학물리학회지:의학물리
    • /
    • 제23권3호
    • /
    • pp.162-168
    • /
    • 2012
  • 양성자 치료에서 치료의 목표를 달성하고 환자의 안전을 제고하기 위해 인체 내 양성자 빔의 분포를 확인하는 것이 중요하다. 양성자 선량분포와 밀접한 관계가 있는 즉발감마선의 2차원 분포 측정을 위하여 본 연구팀에서는 다수의 CsI(Tl) 섬광체가 1차원 종형으로 배열된 검출기 배열과 집속장치 및 다채널 신호처리 장치로 이루어진 측정장치를 개발하고 있다. 이에 본 연구에서 몬테칼로 기반의 MCNPX 코드를 이용하여 최적화된 측정 장치를 설계하고자 하였다. 즉발감마선을 효과적으로 측정하기 위해 CsI(Tl) 섬광체의 크기를 $6{\times}6{\times}50mm^3$로 결정하였으며, 배경감마선의 영향을 최소화하고 빔의 진행방향에서 수직방향으로 발생하는 즉발감마선만 측정하기 위해 집속장치의 구멍 크기는 면적 $6{\times}6mm^2$, 길이 150 mm로 최적화되었다. 150 MeV 양성자 빔에 대한 성능 예측 전산모사연구를 수행한 결과, 본 연구에서 최적화된 측정 장치를 통해 즉발감마선 2차원 분포를 측정할 수 있었으며, 1 mm 오차범위에서 양성자 빔의 비정을 결정할 수 있었다. 이를 바탕으로 현재 다채널의 신호처리 장치를 개발하고 있으며 실제 양성자 빔을 이용한 즉발감마선 분포측정을 통해 측정 장치의 성능을 검증할 것이다.

정수장 유입조류 전처리를 위한 천연조류제거제(W.H.)의 최적주입농도 결정 (Decision Algorithm of Natural Algae Coagulant Dose to Control Algae from the Influent of Water Works)

  • 장여주;정진홍;임현만;윤영한;안광호;장향연;김원재
    • 대한환경공학회지
    • /
    • 제38권9호
    • /
    • pp.482-496
    • /
    • 2016
  • 하천과 호수의 부영양화로 인하여 남조류가 대량으로 증식하게 되면 고유의 생물독소로 인한 위해뿐만 아니라 정수처리 과정에서 경제적 손실을 야기할 가능성이 있다. 현재 상용화되어있는 천연조류제거제인 M사의 W.H. 응집제(이하 W.H.)는 참나무 유래 성분의 살조 및 타감작용을 이용한 응집.부상공정을 통하여 조류를 사전에 제거함으로써 정수공정에 미치는 영향을 효과적으로 저감할 수 있다. 그러나, W.H.를 활용한 응집 부상공정은 정수처리의 전처리공정으로 적용된 사례가 없기 때문에 최적주입농도의 결정기법에 대한 보고 또한 전무한 실정이다. 본 연구에서는 (1) 한강에서 채취한 복합 조류와 (2) 남조류를 선택적으로 대량 배양하여 광조건 하에서 W.H. 투여량 및 조류농도 등의 여러 조건을 변화시키면서 Jar-test를 시행하여 응집 부상공정에서의 조류의 제거기작을 검토하였다. Jar-test 결과를 바탕으로 IBM-SPSS를 활용한 다중회귀분석을 실시하여 최적 W.H. 주입농도를 결정하기 위한 Chl-a 농도와 탁도를 변수로 하는 두 가지 선형식을 도출하였다. 또한 유입수질의 변동에 따라 W.H. 주입농도를 신속하게 결정하고 자동화할 수 있는 자동제어 로직의 프로토타입(Prototype)을 제시하였다.