• Title/Summary/Keyword: Multiple-dose

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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
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    • v.5 no.1
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    • pp.1-6
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    • 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.

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

  • Lim Jong Pil;Park Yeong Seo;Kim Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.2
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    • pp.571-574
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    • 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
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    • v.42 no.4
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    • pp.337-341
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    • 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.

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

  • Ko, Sung-Kwon;Kim, Jae-Soo;Choi, Yong-Eui;Lee, Seung-Jung;Park, Kyeong-Soo;Chung, Sung-Hyun
    • Korean Journal of Pharmacognosy
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    • v.33 no.4 s.131
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    • pp.337-342
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    • 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
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    • v.16 no.9
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    • pp.3741-3745
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    • 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.

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

  • Ham, Kyung-Wan;Kim, Eun-Kyung;Song, Mi-Young;Kwon, Kang-Beom;Song, Je-Ho;Seo, Eun-A;Ryu, Do-Gon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.3
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    • pp.580-584
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    • 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
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    • v.44 no.2
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    • pp.229-237
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    • 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
    • Korean Journal of Clinical Pharmacy
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    • v.31 no.1
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    • pp.35-43
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    • 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.

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

  • Lee, Han Rim;Min, Chul Hee;Park, Jong Hoon;Kim, Seong Hoon;Kim, Chan Hyeong
    • Progress in Medical Physics
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    • v.23 no.3
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    • pp.162-168
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    • 2012
  • In proton therapy, in vivo dose verification is one of the most important parts to fully utilize characteristics of proton dose distribution concentrating high dose with steep gradient and guarantee the patient safety. Currently, in order to image the proton dose distribution, a prompt gamma distribution detection system, which consists of an array of multiple CsI(Tl) scintillation detectors in the vertical direction, a collimator, and a multi-channel DAQ system is under development. In the present study, the optimal design of prompt gamma distribution detection system was studied by Monte Carlo simulations using the MCNPX code. For effective measurement of high-energy prompt gammas with enough imaging resolution, the dimensions of the CsI(Tl) scintillator was determined to be $6{\times}6{\times}50mm^3$. In order to maximize the detection efficiency for prompt gammas while minimizing the contribution of background gammas generated by neutron captures, the hole size and the length of the collimator were optimized as $6{\times}6mm^2$ and 150 mm, respectively. Finally, the performance of the detection system optimized in the present study was predicted by Monte Carlo simulations for a 150 MeV proton beam. Our result shows that the detection system in the optimal dimensions can effectively measure the 2D prompt gamma distribution and determine the beam range within 1 mm errors for 150 MeV proton beam.

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

  • Jang, Yeo-Ju;Jung, Jin-Hong;Lim, Hyun-Man;Yoon, Young H.;Ahn, Kwang-Ho;Chang, Hyang-Youn;Kim, Weon-Jae
    • Journal of Korean Society of Environmental Engineers
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    • v.38 no.9
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    • pp.482-496
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    • 2016
  • Algal blooms of cyanobacteria (blue-green Algae) due to the eutrophication of rivers and lakes can cause not only the damage by its biological toxins but also the economic loss in drinking water treatment. The natural algae coagulant, a commercial product known as W.H. containing the algicidal and allelopathic material derived from oak, can control algal problems proactively through the coagulation flotation process. However, because there have been no applications of the process for pre-treatment in drinking water plants, we could find no report on the optimum injection dose of W.H.. In this study, we have conducted several sets of jar-tests while changing W.H. dose and concentration of chl-a for (1) Han-river samples and (2) subcultured cyanobacteria samples, and monitored the removal mechanisms of algae intensively. Based on these jar-test results, two linear equations with variables of chl-a and turbidity have been deduced to predict the optimal W.H. dose after the multiple regression analysis using IBM-SPSS. Also, prototypes of automatic control logic have been suggested to inject the optimal W.H. dose promptly in response to the variation of water quality.