• 한국수산과학회지
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• 제18권3호
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• pp.206-213
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• 1985

우리나라의 전통적인 수산발효식품 젓갈은 제조시에 첨가되는 식염의 양이 $20\%$ 전후이므로, 최근에는 이러한 식염의 과다섭취가 성인병을 유발시키는 것으로 알려져 있어 식염섭취량을 줄이고 있는 실정이다. 본 연구에서는 식염함량이 낮은 저식염젓갈의 제조와 품질개선을 목적으로 식염의 일부를 KCl로 대체하여 저식염멸치젓과 조기젓을 담그어 재래식젓갈($20\%$ 식염함량)과 숙성중의 화학성분을 비교분석하여 저식염젓의 가공조건을 검토한 결과는 다음과 같다. 멸치젓은 숙성 60일경에, 조기젓은 숙성 90일경에 완전히 익었으며 관능검사결과, KCl을 식염의 $50\%$까지 대체하여 담근 젓은 재래식젓갈에 비해 별손색이 없었으며, 멸치젓 및 조기젓 모두 식염 $4\%$, KCl $4\%$, lactic acid $0.5\%$, sorbitol $6\%$ 및 고추가루 알코올추출물 $4\%$(W/V)를 첨가하여 담근 젓의 품질이 가장 좋았으며 숙성 120일까지도 맛이 좋았다. 그리고 TBA 실험결과, 고추가루 추출물의 항산화성도 확인되었다.

• IMMUNE NETWORK
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• 제12권2호
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• pp.58-65
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• 2012

Background: A cell line with transfected Wilms' tumor protein 1 (WT1) is has been used for the preclinical evaluation of novel treatment strategies of WT1 immunotherapy for leukemia due to the lack of appropriate murine leukemia cell line with endogenous WT1. However, silencing of the transgene occurs. Regarding the effects of hypomethylating agents (HMAs) on reactivation of silenced genes, HMAs are considered to be immune enhancers. Methods: We treated murine WT1- transfected C1498 (mWT1-C1498) with increasing doses of decitabine (DAC) and azacitidine (AZA) to analyze their effects on transgene reactivation. Results: DAC and AZA decreased the number of viable cells in a dose- or time-dependent manner. Quantification of WT1 mRNA level was analyzed by real-time polymerase chain reaction after mWT1-C1498 treated with increasing dose of HMA. DAC treatment for 48 h induced 1.4-, 14.6-, and 15.5-fold increment of WT1 mRNA level, compared to untreated sample, at 0.1, 1, and $10{\mu}M$, respectively. Further increment of WT1 expression in the presence of 1 and $10{\mu}M$ DAC was evident at 72 h. AZA treatment also induced up-regulation of mRNA, but not to the same degree as with DAC treatment. The correlation between the incremental increases in WT1 mRNA by DAC was confirmed by Western blot and concomitant down-regulation of WT1 promoter methylation was revealed. Conclusion: The in vitro data show that HMA can induce reactivation of WT1 transgene and that DAC is more effective, at least in mWT1-C1498 cells, which suggests that the combination of DAC and mWT1-C1498 can be used for the development of the experimental model of HMA-combined WT1 immunotherapy targeting leukemia.

• 약학회지
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• 제34권4호
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• pp.238-243
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• 1990

Pharmacokinetic characteristics of recombinant human interleukin-2 (rH IL-2) wre studied in the rat. First, different doses of rH IL-2 ranging from 6,400 to 1,600,000 U/kg were injected intravenously and the effect of dose size on the pharmacokinetics was examined. There was no dose dependency in the pharmacokinetics of rHIL-2 in the dose range of 6,400-40,000 U/kg. But at the dose of 1,600,000 U/kg, there was a severe hemolysis throughout the experiment and the pharmacokinetic parameters such as Vdss and CLt were significantly increased compared to those obtained from lower doses. It also showed that this drug is hardly distributed to the peripheral tissues and hardly eliminated from the body, since the valume of distribution (Vdss) and total body clearance (CLt) were 45-75 ml/kg and 1-2 ml/min/kg, respectively. The Vdss is close to the actual plasma volume and the CLt is less than glomerular filtration rate (GFR). Therefore it seemed that rH IL-2 is distributed only in the plasma pool and hardly filtered in the kidney due to its very large molecular weight. Second, rH IL-2 was administered to the rat via several routes such as hepatic portal vein (PV), intraperitoneal (IP), peroral (PO) and intranasal (IN) routes. The bioavailabilities (BA) of PV, IP, PO and IN routes were 96.8, 4.9, 0 and 0.1%, respectively. The addition of some nasal absorption enhancers such as taurocholate, taurodeoxycholate, glycocholate and glycodeoxycholate did not increase the BA of intranasaly administered rH IL-2. The result is contrast to the effect of these bile salts on the nasal absorption of ${\alpha}-inteferon$. Considering it together with the pharmacokinetic parameters, very large molecular weight of rH IL-2 seemed again to be the cause to very poor membrane permeability.

• Archives of Pharmacal Research
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• 제26권4호
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• pp.330-337
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• 2003

The effect of sixteen excipients on the transport of recombinant human epidermal growth factor (rhEGF) across Caco-2 cell monolayers was examined at $37^{\circ}C$. The apparent apical to basolateral (A-B) permeability ($P_{app}$) of 30 $\mu$ M rhEGF was $8.15\times 10^{-7}$ cm/sec, indicative of a poor level of absorption in the GI tract. The Papp was 1.7- and 6.3-fold greater than the $P_{app}$ in the basolateral to apical (B-A) direction and the A-B permeability of mannitol, respectively, and decreased dramatically to a negligible level at $4^{\circ}C$, consistent with a receptor mediated transcytosis of rhEGF. The stability of rhEGF was very poor, undergoing more than 85% degradation in 2 h in the transport medium at $37^{\circ}C$. A significant increase in the $P_{app}$ could be achieved by the addition of certain excipients, as exemplified by 23, 21, 20 and 16-fold increases, in the presence of sodium taurochenodeoxycholate (NaTCDC), sodium taurodeoxycholate (NaTDC), sodium glycodeoxycholate (NaGDC) and sodium laurylsulfate (SLS) (all at a concentration of 1 % w/v), respectively. A significant increase in stability could also be achieved by the addition of some of the excipients, as represented by 1 % SLS, which nearly completely stabilized the rhEGF. Unfortunately, however, an increase in the $P_{app}$ of rhEGF could not be achieved without a simultaneous and extensive decrease in the integrity of the cell membranes. Thus, more efficient excipients, that specifically enhance the permeation of rhEGF and do not alter the membrane integrity, should be pursued in order to safely enhance the permeation of rhEGF.

• 대한본초학회지
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• 제31권5호
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• pp.93-98
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• 2016

Objectives : Hwangheuk-san is a complex prescription composed of oriental traditional medicine and has been reported for antioxidant, antimicrobial and anticancer effects in the recent study. Methicillin-resistant Staphylococcus aureus (MRSA) is one of important causes of fatal infectious diseases such as septicemia, endocarditis, toxic shock syndrome, pneumonia, skin and soft tissue infections (SSTIs). S. aureus is reported as being for a variety of human diseases and its epidemiological relevance is mainly due to their ability of becoming highly resistant to common antimicrobials such as tetracycline, penicillin, cphalosporin and aminoglycoside. The objective of this study is to determine the antimicrobial effect of Hwangheuk-san ethanol extracts (HHS) and synergistic effects with antibiotics oxacillin against MRSA.Methods : The antimicrobial activity of HHS was measured by the disc diffusion method, broth microdilution method and the checkerboard dilution test, time-kill curve assay was performed to investigate synergistic effects with antibiotics oxacillin against MRSA.Results : HHS showed antimicrobial activity against MRSA with a MIC value of 125 ㎍/㎖. In the checkerboard test, the interaction of HHS with antibiotics oxacillin produced almost synergy or partial synergy against MRSA. This study showed that HHS reduced the MICs of oxacillin tested, and a remarkable antibacterial effect of HHS, with membrane permeability enhancers.Conclusions : These results suggest that HHS has the antimicrobial effect and synergistic effects with antibiotics oxacillin against MRSA. This study thus can be a valuable source for the development of a new drug with low MRSA resistance.

• Journal of Pharmaceutical Investigation
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• 제38권6호
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• pp.373-380
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• 2008

In order to develop optimal formulation and iontophoresis condition for the transdermal delivery of levodopa, we have evaluated the effect of two permeation enhancers, ethanol and oleic acid in microemulsion, on transdermal delivery of levodopa. In vitro flux studies were performed at $33^{\circ}C$, using side-by-side diffusion cell and full thickness hairless mouse skin. Current density applied was $0.4\;mA/cm^2$ and current was off after 6 hours application. Levodopa was analysed by HPLC at 280 nm. The o/w microemulsions of oleic acid in buffer solution (pH 2.5 & 4.5) were prepared using oleic acid, Tween 80 and ethanol. The existence of microemulsion regions were investigated in pseudo-ternary phase diagrams. Contrary to our expectation, cumulative amount of levodopa transported from microemulsion (pH 2.5) for 10 hours was similar to that from aqueous solution in all delivery methods (passive, anodal and cathodal). When pH of the micro-emulsion was pH 4.5, cumulative amount of levodopa transported for 10 hours increased about 40% (anodal) to 50% (cathodal), when compared to that from aqueous solution. Flux from pH 4.5 microemulsion showed higher value than that from pH 2.5 in all delivery methods. These results seem to indicate that electroosmosis plays more dominant role than electrorepulsion in the flux of levodopa at pH 2.5. The effect of ethanol on iontophoretic flux was studied using pH 2.5 phosphate buffer solution containing 3% or 5% (v/v) ethanol. Flux enhancement was observed in passive and anodal delivery as the concentration of the ethanol increased. Without ethanol, cathodal delivery showed higher flux than anodal delivery. Anodal delivery increased the cumulative amount of levodopa transported 1.6 fold by 5% ethanol after 10 hours. However, in cathodal delivery, no flux enhancement of levodopa was observed during current application and only marginal increase in cumulative amount transported after 10 hours was observed by 5% ethanol. These results seem to be related to the decrease in dielectric constant of the medium and the lipid extraction of the ethanol, which decrease the electroosmotic flow, and thus decrease the flux. Overall, the results provide important insights into the role of electroosmosis and electrorepulsion in the transport of levodopa through skin, and provide some useful informations for optimal formulation for levodopa.

• 대한화장품학회지
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• 제36권2호
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• pp.115-120
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• 2010

피부에서 표피를 통한 물질의 수송은 피부의 여러 가지 보호 작용으로 인해 경피 흡수가 쉽게 이루어지지 않아 결과적으로 생리 활성 성분이 그 효과를 발휘하는 진피층까지 도달하기 어렵다. 본 연구는 피부에서 매우 낮은 농도가 투과되는 친수도가 높은 약물(알부틴)의 경피흡수를 촉진하는 화학적 촉진제의 in vitro 흡수 양상에 대한 연구이다. 화학적 촉진제로 N-methyl-2-pyrrolidone (NMP)을, 경피흡수장치는 Franz diffusion cell을 사용하였다. NMP는 약물의 경피흡수에 상당히 영향을 준다는 것을 알 수 있었다. NMP는 피부 지질층의 유동성에 영향을 주지 않고 약물의 보조흡수제로 작용하여 알부틴의 경피흡수촉진비율을 약 1.3~1.5배 증가 시켰지만 지연 시간의 변화는 없었다. 따라서 NMP는 친수성 생리활성 물질의 효과적인 화학적 경피흡수 촉진제로 작용하였으며, 향후 화장품 제형 및 약물전달체계에 응용이 기대된다.

• KSBB Journal
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• 제20권1호
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• pp.21-25
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• 2005

흔하게 사용되어온 제초제인 paraquat는 파킨슨병의 원인이 될 수 있는 유력한 위험 요소이다. 헴산화효소-1(HO-1)은 산화적 스트레스와 소포체 스트레스의 marker인데, 여러 가지 자극에 의해 heme을 분해하여 biliverdin, 일산화탄소, 철 성분으로 전환시킨다 본 연구에서는 뇌의 흑색질 유래의 도파민 세포주 SN4741에서 paraquat가 시간별, 농도별로 HO-1을 활성화시키는 기작을 조사하였다. HO-1이 Paraquat에 의해 활성화되는 것은 주로 유전자 전사 수준에서 조절되었다. HO-1 유전자의 promoter와 5' enhancer인 El, E2를 결실시킨 실험에서, E2 enhancer가 도파민 세포에서 paraquat에 의한 HO-1 유전자 발현을 유도하는 핵심 부위로 판명되었다 E2 enhancer 부위를 돌연변이 시킨 실험 결과는 전사인자 활성 단백질-1 (AP-1) 결합부위를 통해 HO-1 발현이 유도됨을 밝히게 되었다. 또한, 도파민 세포에서 HO-1 유전자 발현의 조절과 신호전달 과정의 관계를 조사하기 위해 MAP kinase들의 특이적 저해제를 처리하고 paraquat로 자극을 준 결과, JNK 저해제인 SP600125가 가장 현저하게 paraquat에 의한 HO-1 발현을 억제하였다. 결론적으로, 도파민 세포에서 paraquat가 HO-1을 유도하는 데는 E2 enhancer가 중요하게 작용하고, AP-1과 JNK 경로를 통해 HO-1 발현이 조절된다는 사실을 처음으로 밝히게 되었다.

• Archives of Plastic Surgery
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• 제36권5호
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• pp.531-537
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• 2009

Purpose: Alveolar bone grafting has become an essential process in the treatmemt of alveolar cleft patient for stabilization of the maxillary arch, elimination of oronasal fistula, the reconstruction of the soft tissue nasal base support, and creation of bony support for tooth eruption for implant. The use of Autologous iliac cancellous bone is preferable because of the adequate quantity and high osteoinductive potential. However, even with iliac bone, insufficient osteoregeneration and absorption occur due to several factors such as the patient's age, cleft width, functional stress, and others. In order to increase osteoregeneration where the iliac bone is placed, the present study is associated with bone marrow aspirate (BMA). The experimental study evaluated the efficacy of osteoregeneration in normal cleft rabbits when alveolar bone grafting was performed with autologous iliac corticocancellous bone. Methods: Twenty - four New Zealand White rabbits were divided randomly into 2 groups (BMA, control). All animals underwent harvesting of corticocancellous bone graft from the right posterior iliac crest via standard surgical technique. $1m{\ell}$ of BMA were obtained by scraping the needle and aspirate with $10m{\ell}$ syringe from the contralateral iliac bone wall. The muco - periosteal flap on the palate was elevated. A mixture of Equal bone's volumes with BMA and saline as its control was inserted into the cleft. Animals were sacrificed at 2, 4, and 8 weeks and maxilla was harvested for dental peri - apical X-ray, bone matrix density (BMD),and histologic analysis. Result: BMD of regenerated bone to the cleft in the rabbits was higher than that of the control rabbits. X-ray, histologic analysis showed that increased osteoregeneration and low absorption rate were observed in the BMA group. Conclusion: Our experimental study showed BMA enhanced the osteoregeneration and survival rate of alveolar bone grafting. BMA is easy to extract & cost - time effective. So it can be an effective enhancers for bone grafting mixtures.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제5권1호
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• pp.39-50
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• 2002

Hepatitis B viral infection which affect about 10% of Korean population manifests asymptomatic carrier, chronic hepatitis and liver cirrhosis and even associates with hepatocellular carcinoma. Clinical manifestations induced by hepatitis B virus vary depending on the degree of immune response by cytotoxic T cells against viral epitope-presenting liver cells. Since hepatitis B virus presents high rate of mutaton that might change the presented epitope and eventually alter immune response, viral mutations, especially in promoters and enhancers, have an important implication in hepatic inflammation and viral replication. To identify mutations related to the hepatic inflammation, we investigated sequence variations of hepatitis B viral promotor regions in the presence or absence of symptoms in hepatitis B carriers. For this, sera from persistently hepatitis B virus-infected mother-child pairs were collected. After PCR amplifiation of all hepatitis B viral promoters (C promoter, S1 promoter, S2/S promoter, X promoter) using serum DNA from each pair, viral promotors were sequenced by automatic sequencer and then sequence data were analyzed by ClustalW. In most cases, the dominant type of maternal virus was transmitted to the child. However, in some children, some new host specific viral variants could be observed in Cp, S1p and S2/Sp. The mutations in C promoter did not seem to be vertically transmitted but arose in new host independently after the wild type had been transmitted. Enhancer I containing X promoter revealed high host specific variations as has been reported before. Two S promoters, S1p and S2/Sp, have shown some point mutations in children, but no deletion mutations were detected as in chronic hepatitis patients in whom deletion mutations are frequently found. In conclusion, the children with the vertically transmitted hepatitis B virus mostly retain the dominant type virus that had been transmitted. However, host specific variants tended to accumulate over time, possibly as clinical symptoms develop.