• 제목/요약/키워드: Prolonged release

검색결과 105건 처리시간 0.023초

리포좀에 봉입된 아클라루비신의 약물동태, 세포독성, 항암효과 및 비장/혈구 세포독성 (Pharmacokinetics, Cell Toxicity, Antitumor Activity and Spleen/Blood Cell Toxicity of Aclarubicin-entrapped Liposomes)

  • 박목순;박진규;이계원;명평근;석대은;황성주;지웅길
    • 약학회지
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    • 제42권3호
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    • pp.275-283
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    • 1998
  • Aclarubicin(ACL)-entrapped freeze dried liposomes were prepared using Microfludizer to attain a sustained release at targeted organs in a prolonged time so that it can reduce th e side effect and maximize the therapeutic effect. The freeze-dried liposomes were evaluated for pharmacokinetics, antitumor activity against Sarcoma 180, cytotoxicity against L1210 and A549 tumor cells, spleen toxicity and myelosuppressive action. The $AUC_{0{\rightarrow}8hr}$ values were $122{\pm}42,\;382{\pm}140,\;419{\pm}171,\;835{\pm}206\;and\;443{\pm}309{\mu}g{\cdot}min/ml$ for free ACL. ACL-liposome formulation I, II, III and IV, respectively. Cytotoidcity of ACL-entrapped liposomes against L1210 and A549 tumor cells was 2-4 times higher than that of free aclarubicin. ACL-liposome formulation I(PC/CHOL/TA) showed the most potent antitumor activity against Sarcoma 180 in mice. The loss of body weight was much smaller with ACL-entrapped liposomes than free ACL after I.p. injection at a dose of 2 mg/kg/day. Compared to free ACL, ACL-entrapped liposomes expressed a lower and delayed spleen toxicity up to 5th day after I.v. administration. Myelosupperssion seemed to be lower with ACL-entrapped liposome of PC/PC-hydrate/CHOL/TA (formulation III) than free aclarubicin.

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Effects of Exogenous Bovine Somatotropin on Mammary Function of Late Lactating Crossbred Holstein Cows

  • Tanwattana, P.;Chanpongsang, S.;Chaiyabutr, N.
    • Asian-Australasian Journal of Animal Sciences
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    • 제16권1호
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    • pp.88-95
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    • 2003
  • The objective of the present study was to determine the effect of exogenous bovine somatotropin on the mammary function in late lactating crossbred Holstein cows. Twelve 87.5% late lactating Holstein cows, approximately 30 weeks postpartum, were divided into two groups of 6 animals each. Animals in the control group were given sodium bicarbonate buffer by subcutaneous injection, while animals in the treated group were given recombinant bovine somatotropin (bST) by subcutaneous injection with 500 mg of bST (14 day prolonged-release bST). After bST injection, milk yield significantly increased from the control level on day 8 to day 20 (p<0.05) with a concomitant increase in mammary blood flow (p<0.01). An increase in mammary blood flow in response to bST treatment was greater than an increase in milk production. An increased plasma concentration of IGF-I coincided with an increase in mammary blood flow in animals treated with bST. There were no significant changes in the concentration of arterial plasma glucose concentration, the arteriovenous concentration difference (A-V difference) and mammary extraction ratio while the mammary glucose uptake increased when compared to the control group. The concentration of arterial plasma triglyceride decreased throughout the experimental period in animals give bST. The plasma concentration of acetate, and the mammary uptake for acetate significantly increased (p<0.05) after bST treatment. The action of bST did not affect the plasma concentration, A-V difference and extraction ratio across the mammary gland for $\beta$-hydroxybutyrate. The concentrations of milk fat and lactose tended to increase during bST treatment. Milk protein concentration initially increased in the first few days and decreased after bST injection when compared to the pretreated period. The present results indicated that bST could affect the mammary function in late lactating cows by increase in milk yield involving changes in both extra-mammary and intra-mammary mechanisms. The exogenous bST exerted its galactopoietic action through an increase in circulating IGF-I of the late lactating Crossbred Holstein cattle.

29-kDa FN-f inhibited autophagy through modulating localization of HMGB1 in human articular chondrocytes

  • Hwang, Hyun Sook;Choi, Min Ha;Kim, Hyun Ah
    • BMB Reports
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    • 제51권10호
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    • pp.508-513
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    • 2018
  • Fibronectin fragments found in the synovial fluid of patients with osteoarthritis (OA) induce the catabolic responses in cartilage. Nuclear high-mobility group protein Box 1 (HMGB1), a damage-associated molecular pattern, is responsible for the regulation of signaling pathways related to cell death and survival in response to various stimuli. In this study, we investigated whether changes induced by 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) in HMGB1 expression influences the pathogenesis of OA via an HMGB1-modulated autophagy signaling pathway. Human articular chondrocytes were enzymatically isolated from articular cartilage. The level of mRNA was measured by quantitative real-time PCR. The expression of proteins was examined by western blot analysis, immnunofluorescence assay, and enzyme-linked immunosorbent assay. Interaction of proteins was evaluated by immunoprecipitation. The HMGB1 level was significantly lower in human OA cartilage than in normal cartilage. Although 29-kDa FN-f significantly reduced the HMGB1 expression at the mRNA and protein levels 6 h after treatment, the cytoplasmic level of HMGB1 was increased in chondrocytes treated with 29-kDa FN-f, which significantly inhibited the interaction of HMGB1 with Beclin-1, increased the interaction of Bcl-2 with Beclin-1, and decreased the levels of Beclin-1 and phosphorylated Bcl-2. In addition, the level of microtubule-associated protein 1 light chain 3-II, an autophagy marker, was down-regulated in chondrocytes treated with 29-kDa FN-f, whereas the effect was antagonized by mTOR knockdown. Furthermore, prolonged treatment with 29-kDa FN-f significantly increased the release of HMGB1 into the culture medium. These results demonstrated that 29-kDa FN-f inhibits chondrocyte autophagy by modulating the HMGB1 signaling pathway.

관교의치용 Au-Ag-Cu-Pt-Zn 합금의 시효경화성과 관련된 상변태와 입계석출 (Phase transformation and grain boundary precipitation related to the age-hardening of an Au-Ag-Cu-Pt-Zn alloy for crown and bridge fabrication)

  • 조미향
    • 대한치과기공학회지
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    • 제34권4호
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    • pp.345-352
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    • 2012
  • Purpose: The age-hardening mechanism of an Au-Ag-Cu-Pt-Zn alloy for crown and bridge fabrication was investigated by means of hardness test, X-ray diffraction study and field emission scanning electron microscopic observation. Methods: Before hardness testing, the specimens were solution treated and then were rapidly quenched into ice brine, and were subsequently aged isothermally at $400-450^{\circ}C$ for various periods of time in a molten salt bath and then quenched into ice brain. Hardness measurements were made using a Vickers microhardness tester. The specimens were examined at 15 kV using a field emission scanning electron microscope. Results: By the isothermal aging of the solution-treated specimen at $450^{\circ}C$, the hardness increased rapidly in the early stage of aging process and reached a maximum hardness value. After that, the hardness decreased slowly with prolonged aging. However, the relatively high hardness value was obtained even with 20,000 min aging. By aging the solution-treated specimen, the f.c.c. Au-Ag-rich ${\alpha}_0$ phase was transformed into the Au-Ag-rich ${\alpha}_1$ phase and the AuCu I ordered phase. Conclusion: The hardness increase in the early stage of aging process was attributed to the formation of lattice strains by the precipitation of the Cu-rich phase and then subsequent ordering into the AuCu I-type phase. The decrease in hardness in the later stage of aging process was due to the release of coherency strains by the coarsening of tweed structure in the grain interior and by the growth and coarsening of the lamellar structure in the grain boundary. The increase of inter-lamellar space contributed slightly to the softening compared to the growth of lamellar structure toward the grain interior.

Ursodeoxycholic Acid Inhibits Pro-Inflammatory Repertoires, $IL-1{\beta}$ and Nitric Oxide in Rat Microglia

  • Joo, Seong-Soo;Kang, Hee-Chul;Won, Tae-Joon;Lee, Do-ik
    • Archives of Pharmacal Research
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    • 제26권12호
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    • pp.1067-1073
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    • 2003
  • Ursodeoxycholic acid (UDCA) is a non-toxic, hydrophilic bile acid in widespread clinical use mainly for acute and chronic liver disease. Recently, treatment with UDCA in hepatic graft-versus-host disease has been given in immunosuppressive therapy for improvement of the biochemical markers of cholestasis. Moreover, it has been reported that UDCA possesses immunomodulatory effects by the suppression of cytokine production. In the present study, we hypothesized that UDCA may inhibit the production of the pro-inflammatory cytokine, IL-1$\beta$, and nitric oxide (NO) in microglia. In the study, we found that 100 $\mu$ g/mL UDCA effectively inhibited these two pro-inflammatory factors at 24 hand 48 h, compared to the $A\beta$42-pretreated groups. These results were compared with the LPS+UDCA group to confirm the UDCA effect. As microglia can be activated by several stimulants, such as $A\beta$42, in Alzheimers brain and can release those inflammatory factors, the ability to inhibit or at least decrease the production of IL-1$\beta$ and NO in Alzheimers disease (AD) is essential. Using RT-PCR, ELISA and the Griess Reagent System, we therefore found that UDCA in $A\beta$42 pre-treated cultures played a significant role in suppressing the expression or the production of IL-1$\beta$ and NO. Similarly, lipopolysaccharide (LPS) did not activate microglia in the presence of UDCA. Moreover, we found that UDCA exhibits a prolonged effect on microglial cells (up to 48 h), which suggests that UDCA may play an important role in chronic cell damage due to this long effect. These results further imply that UDCA could be an important cue in suppressing the microglial activation stimulated by massive AD peptides in the AD progressing brain.

Large Scale Experiments Simulating Hydrogen Distribution in a Spent Fuel Pool Building During a Hypothetical Fuel Uncovery Accident Scenario

  • Mignot, Guillaume;Paranjape, Sidharth;Paladino, Domenico;Jaeckel, Bernd;Rydl, Adolf
    • Nuclear Engineering and Technology
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    • 제48권4호
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    • pp.881-892
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    • 2016
  • Following the Fukushima accident and its extended station blackout, attention was brought to the importance of the spent fuel pools' (SFPs) behavior in case of a prolonged loss of the cooling system. Since then, many analytical works have been performed to estimate the timing of hypothetical fuel uncovery for various SFP types. Experimentally, however, little was done to investigate issues related to the formation of a flammable gas mixture, distribution, and stratification in the SFP building itself and to some extent assess the capability for the code to correctly predict it. This paper presents the main outcomes of the Experiments on Spent Fuel Pool (ESFP) project carried out under the auspices of Swissnuclear (Framework 2012-2013) in the PANDA facility at the Paul Scherrer Institut in Switzerland. It consists of an experimental investigation focused on hydrogen concentration build-up into a SFP building during a predefined scaled scenario for different venting positions. Tests follow a two-phase scenario. Initially steam is released to mimic the boiling of the pool followed by a helium/steam mixture release to simulate the deterioration of the oxidizing spent fuel. Results shows that while the SFP building would mainly be inerted by the presence of a high concentration of steam, the volume located below the level of the pool in adjacent rooms would maintain a high air content. The interface of the two-gas mixture presents the highest risk of flammability. Additionally, it was observed that the gas mixture could become stagnant leading locally to high hydrogen concentration while steam condenses. Overall, the experiments provide relevant information for the potentially hazardous gas distribution formed in the SFP building and hints on accident management and on eventual retrofitting measures to be implemented in the SFP building.

(AO)$_2,$ SBR과 $A_2O$ SBR의 유기물, 질소 및 인의 제거에 관한 연구 (A Study on the Organic, Nitrogen and Phosphorus Removal in (AO)$_2$ SBR and $A_2O$ SBR)

  • 박영식;우형택;김동석
    • 한국환경보건학회지
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    • 제31권4호
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    • pp.340-348
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    • 2005
  • Laboratory scale experiments were conducted to compare the performance of two types of sequencing batch reactor(SBR) systems, anoxic-oxic-anoxic-oxic $((AO)_2)$ SBR and anoxic-oxic-anoxic $(A_2O)$ SBR on the biological nitrogen and phosphorus removal. Also, the profiles of DO and pH in reactors were used to monitor the biological nutrient removal in two SBRs. The break point in the pH and DO curves at the oxic period coincided with the end of nitrifying activity at about 1 h 30 min in oxic phase, and the change in pH appears to be related to nitrate concentration. The TOC removal efficiency in $A_2O$ SBR was higher than that in $(AO)_2$ SBR. The denitrification was completed at the influent period. The 2nd non-aeration and aeration periods were not necessary for the nitrogen and phosphorus removal because of the low influent TOC concentration in this study. The release and uptake of phosphorus in $AO_2$ SBR was much higher than that in $(AO)_2SBR.$ In order to uptake more phosphorus, the 1st aeration period in $A_2O$ SBR should be prolonged.

Characterization of intracellular Ca2+ mobilization in gefitinib-resistant oral squamous carcinoma cells HSC-3 and -4

  • Kim, Mi Seong;Kim, Min Seuk
    • International Journal of Oral Biology
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    • 제46권4호
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    • pp.176-183
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    • 2021
  • Oral squamous cell carcinoma (OSCC) metastasis is characterized by distant metastasis and local recurrence. Combined chemotherapy with cisplatin and 5-fluorouracil is routinely used to treat patients with OSCC, and the combined use of gefitinib with cytotoxic drugs has been reported to enhance the sensitivity of cancer cells in vitro. However, the development of drug resistance because of prolonged chemotherapy is inevitable, leading to a poor prognosis. Therefore, understanding alterations in signaling pathways and gene expression is crucial for overcoming the development of drug resistance. However, the altered characterization of Ca2+ signaling in drug-resistant OSCC cells remains unclear. In this study, we investigated alterations in intracellular Ca2+ ([Ca2+]i) mobilization upon the development of gefitinib resistance in human tongue squamous carcinoma cell line (HSC)-3 and HSC-4 using ratiometric analysis. This study demonstrated the presence of altered epidermal growth factor- and purinergic agonist-mediated [Ca2+]i mobilization in gefitinib-resistant OSCC cells. Moreover, Ca2+ content in the endoplasmic reticulum, store-operated calcium entry, and lysosomal Ca2+ release through the transient receptor potential mucolipin 1, were confirmed to be significantly reduced upon the development of apoptosis resistance. Consistent with [Ca2+]i mobilization, we identified modified expression levels of Ca2+ signaling-related genes in gefitinib-resistant cells. Taken together, we propose that the regulation of [Ca2+]i mobilization and related gene expression can be a new strategy to overcome drug resistance in patients with cancer.

과수해충 페로몬 연구의 현황과 향후 방향 (Current Status and Future Directions of Pheromone Research on Orchard Pests in Korea)

  • 양창열
    • 한국응용곤충학회지
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    • 제61권1호
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    • pp.51-62
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    • 2022
  • 많은 해충이 과수의 다양한 조직을 가해하여 국내 과수산업을 위협하고 있다. 경제적으로 중요한 과수 해충의 방제는 일반적으로 화학 살충제에 의존하고 있다. 환경과 인류 건강에 미치는 살충제의 영향에 대한 우려가 증가함에 따라 환경 친화적인 해충방제 전략이 시급하게 필요한 실정이다. 과수 해충의 페로몬은 교미교란이나 대량포획과 같이 환경적으로 안전한 방제 체계를 끌어낼 수 있다. 본 종설은 과수 해충 51종에서 알려진 페로몬의 유형과 성분을 요약한다. 장님노린재과, 진딧물과, 깍지벌레과, 가루깍지벌레과, 풍뎅이과, 혹파리과 및 씨살이좀벌과에 속하는 14종과 나비목의 26종은 암컷이 성페로몬을 생산하여 수컷을 유인한다. 반대로 호리허리노린재과, 노린재과, 총채벌레과 및 하늘소과에 속하는 11종은 수컷이 집합페로몬을 생산하여 암컷과 수컷 모두를 유인한다. 향후 과수 해충 관리에서 페로몬과 다른 신호화학물질의 사용을 확대하기 위해서는 새로운 해충의 페로몬, 주요 해충의 카이로몬, 장기간 페로몬 방출용 교미교란제 및 대량포획을 위한 트랩 디자인과 트랩 설치에 관한 연구가 필요할 것으로 보인다.

구리 기반 표면코팅 및 산화수에 따른 항균·항바이러스 특성 (Copper-based Surface Coatings and Antimicrobial Properties Dependent on Oxidation States)

  • 고상원
    • 공업화학
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    • 제34권5호
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    • pp.479-487
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    • 2023
  • 구리(Cu)는 저렴한 비용으로 용이하게 도입이 가능하여 다양한 소재 표면에 살균 코팅제로 쓰이고 있다. 자연적 산화 반응이 구리의 효능을 손상시키지 않아 장기간 노출 조건에서도 항균 성능을 유지할 수 있다. 더 나아가 구리 화합물은 그람 음성균 및 그람 양성균 뿐만 아니라, 병원성 효모, 외피 보유 및 외피 미보유 타입의 바이러스에 대해 모두 폭넓은 살균 효과를 보인다. 구리 코팅 표면의 접촉 살균은 구리의 침투로 단백질 변성을 일으키고 세포막 손상으로 뉴클레오티드 및 세포질 등의 내용물이 용출되게 한다. 또한 구리 산화환원 활성에 의한 활성 산소종 생성으로 효소작용을 억제하고 DNA를 파괴하여 세포를 영구적으로 손상시킨다. 구리는 안정한 금속 성질 때문에 나노입자, 이온, 복합물, 합금 등의 여러 형태로 쓰이고 있으며 코팅 방법이 다양하다. 본 총설에서는 구리 이온과 구리 산화물의 대표적인 표면 도입 방법을 살펴보고 구리 산화수에 따른 항균·항바이러스 특성을 다루고자 한다.