• Title/Summary/Keyword: $P2Y_{12}$ Inhibitors

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The effect of cyclic AMP on the growth of Toxoplasma gondii in vitro (Cyclic AMP대사가 Toxoplasma gondii의 체외 배양에 미치는 영향)

  • 최원영;남호우
    • Parasites, Hosts and Diseases
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    • v.28 no.2
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    • pp.71-78
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    • 1990
  • To assess the role of cAMP on the growth and proliferation of Toxoplasma in HL-60 cells we tested the effect of exogenous cAMP and cAMP analogues to the co-culture system of Toxoplasma and HL-60 cells. cAMP, dbcAMP, and br-cAMP stimulated the growth of Texoplasma at a specific concentration, i.e., 100 mM, l00 mM, and 10-1 mM, respectively. There were differences in growth induction kinetics and in the rate of promotion. These results were further verified by treating the co-culture with adenylate cyclase activator, pNHppG, cAMP phosphodiesterase activators, imidasole and A23187, and cAMP phosphodiesterase inhibitors, IBMX, compound 48/80, and theophylline, separately. When the cytosolic cAMP levels increased by the reagents mentioned above, Toxoplasma in the cytoplasm of HL-60 cells stimulated to proliferate more rapidly with concentration-dependent modes compared to the control, and vice versa. It is suggested that some mechanisms are activated by the high levels of cAMP in the cytoplasm, which result in the stimulation of Toxoplasma proliferation.

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The Effect of Feeding Different Levels of Sardine Fish Silage on Broiler Performance, Meat Quality and Sensory Characteristics under Closed and Open-sided Housing Systems

  • Al-Marzooqi, W.;Al-Farsi, M.A.;Kadim, I.T.;Mahgoub, O.;Goddard, J.S.
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.12
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    • pp.1614-1625
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    • 2010
  • Two experiments were conducted to evaluate the use of fish silage prepared from Indian oil sardines, Sardinella longiceps, as partial replacement of soybean meal as a sole source of protein for growing broiler chickens. The main objective of Experiment 1, an ileal digestibility assay, was to assess the nutritional value of fish silage compared with soybean meal for feeding broiler chickens. The two test ingredients, soybean meal and dried fish silage, were incorporated into semi-synthetic diets, as the only component containing protein. The ileal digestibility coefficients of amino acids of fish silage were considerably higher than those of soybean meal (p<0.001). The lower digestibility of amino acids from soybean meal was related to the presence of anti-nutritional factors such as trypsin inhibitors. Fish silage had higher levels of sulphur-containing amino acids than soybean meal. The objective of Experiment 2, a growth study, was to evaluate the effect of feeding fish silage on performance and meat quality characteristics of broiler chickens raised under closed and open-sided housing systems. Four diets containing various levels of fish silage (0, 10, 20 and 30%) were evaluated. Daily feed intake, body weight gain and feed conversion ratio were measured. At the end of Experiment 2, 96 birds were randomly selected and slaughtered to evaluate meat quality characteristics. Housing type had significant effects on feed intake and body weight gain (p<0.01). Birds in the open-sided house consumed 4.7% less amount of feed and gained 10.6% less than their counterparts in a closed house. Birds in both houses fed diets containing 10 and 20% fish silage gained more than birds fed 30% fish silage. The current study produced evidence that fish silage can replace up to 20% of soybean meal in broiler diets without affecting either growth performance or the sensory quality of broiler meat.

The Modulation of Radiosensitivity by Combined Treatment of Selective COX-2 Inhibitor, NS 398 and EGF Receptor Blocker AG 1478 in HeLa Cell Line (선택적 COX-2 억제제 NS 398과 EGF 수용체 차단제 AG 1478의 복합투여가 HeLa 세포주의 방사선 감수성에 미치는 영향)

  • Youn Seon Min;Oh Young Kee;Kim Joo Heon;Park Mi Ja;Seong In Ock;Kang Kimun;Chai Gyuyong
    • Radiation Oncology Journal
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    • v.23 no.1
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    • pp.51-60
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    • 2005
  • Purpose : Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. Materials and Methods : Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy ($SF_2$) and dose enhancement ratio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. Results : A cooperative effect were observed on the apoptosis of the HeLa ceil line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of $22.70\%$ compare with combination of the one drug with radiation, apoptosis of $8.49\%$. In cell cycle analysis, accumulation of cell on $G_0/G_l$ phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity on a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and $SF_2$ of 0.12 but the combination of one drug with radiation was not enhanced radlosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 (p=0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. Conclusion : Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation, suppression of tumor cell cycle progression and inhibition of anti-apoptotic proteins.

Proteinase activity in the isolates of Trichomonas vaginalis according to their pathogenicity (질트리코모나스의 병원성과 단백 분해 효소와의 상관성)

  • 심영기;박경희
    • Parasites, Hosts and Diseases
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    • v.31 no.2
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    • pp.117-128
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    • 1993
  • Ten axonic isolates of Trichomonns uaginolis were subcutaneously injected to the BALB/c mice in order to assess their pathogenicity by means of so-called "mouse assay" method. All the isolates revealed neutral and acid proteinase activities both in their Iysates and in culture media, but the specific activities of both proteinases in the severely pathogenic group were significantly higher than the mildly pathogenic group (p < 0.05). In the SDS-PAGE system in which the electrophoretic gels contained 0.4% gelatin as the substrate, five different handing patterns of trichomonal proteinases were detected, and the patterns were closely related with the pathogenicity of the isolates of T. vosinalis. All five bands might be regarded as cysteine proteinases group in the inhibitor assays. The cytotoxicity of the Iysates of T. vaginalis to the target Chinese hamster ovarian (CHO) cell line was also significantly different according to the pathogenicity of the isolates, and generally lower in the Iysates treated with cysteine proteinase inhibitors than in the control Iysates. In summarizing the results, it might be considered that the proteinases of T.vaginalis showing five electrophoretic banding patterns are closely related with the pathogenicity and cytotoxicity of the isolates of T. voginolis.

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Effects of a Pan Selectin Inhibitor on Renal Injury after Kidney Transplantation in Dogs (개의 신장이식에서 신장손상에 대한 Pan Selectin Inhibitor의 효과)

  • Woo, Heung-Myong
    • Journal of Veterinary Clinics
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    • v.19 no.3
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    • pp.299-302
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    • 2002
  • Selectins are differentially expressed carbohydrate binding proteins involved in the initiation of tissue inflammation by mediating the rolling and tethering of leukocytes on the vascular endothelium. This primary event in initiation of inflammation, as occurs during reperfusion injury, can be therapeutically targeted using selectin inhibitors, which generally block binding of sLex to E-, P-, and L-selectins. The objective of this study was to determine the role of selectins in renal ischemia/reperfusion injury after kidney transplantation. Canine kidneys were subjected to 60-min warm ischemia, flushed with UW solution, cold stored for 24 h, and autotransplanted into the nephrectomized donor. Renal autografts were monitored for 7 days by serum creatinine in the first study and by histology and myeloperoxidase activity after 4-hour reperfusion in the second study. In each study, one group of animals received TBC1269 (selectin inhibitor) and the other received saline vehicle. Serum creatinine rose quickly after transplantation and was not different between the groups. TBC1269 abolished a reperfusion-induced 2-fold increase in renal cortex neutrophil infiltration and improved histologic signs of ischemia after 4 hours of reperfusion. Selectin blockade does not improve the course of injury caused by warm renal ischemia. A minor benefit associated with the inhibition of early inflammation during reperfusion after kidney transplantation seems to occur.

Participation of nitric oxide pathways in interleukin 1$\beta$-induced mechanical allodynia in the orofacial area of rats

  • Kang, Young-M.;Lee, Min-K.;Yang, Gwi-Y.;Bae, Yong-C.;Ahn, Dong-K.
    • International Journal of Oral Biology
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    • v.34 no.1
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    • pp.1-6
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    • 2009
  • The purpose of the present study was to examine the role of peripheral nitric oxide (NO) pathways in the onset of interleukin (IL)-1$\beta$-induced mechanical allodynia in the orofacial area. Experiments were carried out on male Sprague-Dawley rats weighing 230-280 gm and surgical procedures were performed under pentobarbital sodium (40 mg/kg, i.p.). Under anesthesia, a polyethylene tube (PE10) was implanted into the subcutaneous area of one vibrissa pad, which enabled the injection of IL-1$\beta$ or other chemicals. We subcutaneously injected 50 ${\mu}L$ of IL-1$\beta$ into a vibrissa pad through the implanted polyethylene tube with a 100 ${\mu}L$ Hamilton syringe. After the administration of 0.01, 0.1, 1, or 10 pg of IL-1$\beta$, withdrawal behavioral responses were examined. The subcutaneous injection of saline had no effects on the air-puff thresholds. Following the subcutaneous injection of 0.01, 0.1, 1, or 10 pg of IL-1$\beta$, the threshold of air puffs decreased significantly to 12 $\pm$ 3, 7 $\pm$ 2, 5 $\pm$ 1, or 5 $\pm$ 1 psi, respectively, in a dose dependent manner. Pretreatment with L-NAME, a nitric oxide synthase (NOS) inhibitor, blocked IL-1$\beta$-induced mechanical allodynia. However, neither D-NAME, an inactive isomer of L-NAME, nor vehicle affected the IL-1$\beta$-induced mechanical allodynia. Subcutaneous injection of IL-1$\beta$ increased the number of c-fos-like immunoreactive neurons, whereas pretreatment with L-NAME decreased this number, in the trigeminal caudal nucleus. These results suggest that pro-inflammatory cytokines and NO are important contributors to the pathogenesis of persistent and exaggerated IL-1$\beta$-induced pain states. Based on these observations, peripheral application of NOS inhibitors may be of therapeutic value in treating pain disorders in the clinic.

Inhibition of Browning in Yam Fresh-cut and Control of Yam-putrefactive Bacterium Using Acetic Acid or Maleic Acid. (초산 및 말레산을 이용한 생마 신선편이 갈변억제 및 생마 저온부패균의 제어)

  • Ryu, Hee-Young;Kwun, In-Sook;Park, Sang-Jo;Lee, Bong-Ho;Sohn, Ho-Yong
    • Microbiology and Biotechnology Letters
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    • v.35 no.2
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    • pp.135-141
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    • 2007
  • To increase the consumer acceptability of yam and the shelf-life of fresh-cut yam, organic acid-treated fresh-cut yam was prepared. When uncontaminated fresh-cut yam was stored at $4^{\circ}C$ for 14 days after treatment with 1% (v/w) organic acids, the browning and microbial putrefaction of fresh-cut yam were inhibited by treatment of acetic acid or maleic acid, whereas treatment of citric acid and ascorbic acid, commonly used browning inhibitors in food industry, did not show apparent effects on the browning and putrefaction of yam. The Inhibitory effects of acetic acid or maleic acid were superior than those of NaOCl (100 ppm), hydrogen peroxide (100 ppm) or commercially available washing solution. Also, treatments of 1% acetic acid, or 1% maleic acid Into artificially-contaminated yam $(10^5\;CFU/g-yam)$ showed strong inhibition of browning and putrefaction during long term storage at $4^{\circ}C$. The growth inhibition test indicated that 0.1% is enough to inhibit the growth of psychrotrophic yam-putrefactive Pseudomonas sp., and treatment of 0.1% acetic acid, or 0.1% maleic acid inhibited the browning and microbial putrefaction of fresh-cut yam. Our results suggested long-term distribution of yam or other root crops products is possible by treatment of organic acid, such as acetic acid, combined with aseptic vacuum packaging technology.

Antioxidative Effect and Neuraminidase Inhibitory Activity of Polyphenols Isolated from a New Korean Red Waxy Sorghum (Sorghum bicolor L. cv. Hwanggeumchalsusu) (황금찰수수(Sorghum bicolor L. cv. Hwanggeumchalsusu) 유래 에탄올 추출물 및 폴리페놀계 화합물의 항산화 활성 및 뉴라미니데이즈 억제 효과)

  • Ra, Ji-Eun;Seo, Kyung Hye;Ko, Jee Yeon;Lee, Mi-Ja;Kang, Hyeon Jung;Kim, Sun Lim;Chung, Ill-Min;Seo, Woo Duck
    • Journal of Life Science
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    • v.25 no.7
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    • pp.786-794
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    • 2015
  • To identify nutritional and therapeutic properties of the new Korean red waxy sorghum cultivar ‘Hwanggeumchalsusu (HGC)’, we assayed the antioxidative effects and neuraminidase inhibitory activity. A methanol and 70% ethanol extract of HGC exhibited strong antioxidative effects (IC50 values of 83.2±2.7 for DPPH) and 85.6±2.4 μg/ml for ABTS) and neuraminidase (ND) inhibitory activity (IC50 values of 1.8±0.1 from extracted with methanol and 3.4±0.1 μg/ml from extracted with 70% ethanol) compared with that of the control, noncolored sorghum cultivar ‘Huinchalsusu (HC)’ (IC50> 200 μg/ml). We isolated nine polyphenols, Gallic acid (1), Protocatecuic acid (2), p-Hydroxy benzoic acid (3), Vanillic acid (4), Caffeic acid (5), Ferulic acid (6), Luteolinidin (7), Apigeninidin (8), Luteolin (9), from the HGC - methanol extract, to determine whether they were the active components Luteolinidin of one kind of polyphenols from the HGC, exhibited significant antioxidative effects (IC50 values of 10.9±0.5 μM for DPPH and 8.6 0.6 μM for ABTS) and neuraminidase (ND) inhibitory activity (IC50 values of 26.3±0.6) showed noncompetitive inhibition model. The binding affinity of the ND inhibitors in molecular docking experiments correlated with their ND inhibitory activities. These results suggest that HGC may be utilized to serve as a potential effective antioxidant and inhibitor of ND.

Research of Corrosion Control Technology for the Product Water of SWRO(Seawater Reverse Osmosis) by using liquid lime (액상소석회를 이용한 SWRO 생산수의 부식제어 연구)

  • Kim, Min-Chul;Hwang, Kyu-Won;Woo, Dal-Sik;Yoon, Seok-Min;Kwak, Myung-Hwa
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.12 no.1
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    • pp.529-536
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    • 2011
  • In this study, we confirmed that the SWRO(Sea Water Reverse Osmosis) production water has more hard corrosiveness than the tap water by fundamental experiment. According to the result, the target of this study was aimed at developing maintenance and anti-corrosion method. In the early stages of the research, batch tests using mild steel coupons and electrochemical experiments were applied to compare the corrosiveness between SWRO production water and the tap water. After then, two corrosion control methods for SWRO production water were applied. Liquid lime($Ca(OH)_2$) and Carbon Dioxide($CO_2$) were inserted and compared with the combination of liquid lime with phosphate corrosion inhibitor and carbon dioxide. The water qualities were evaluated through LSI(Langelier Saturation Index) and proper injection ratio was deduced by the result. Since then, simulated loop system test were performed to evaluate anti-corrosion effect depending on corrosion inhibitors. Subsequently, carbon steel pipes equipped at the loop system were detached for SEM, EDX and XRD analysis to acquire quantitative and qualitative data of the major corrosion products inside the pipes. In conclusion, the controled groups with anti-corrosion techniques applied were effective by appearing 97.4% and 90.9% of improvements in both case of liquid lime and the liquid lime with a phosphate corrosion Inhibitor. furthermore, major components of scale were iron oxides, on the other hand, protective effect of film formation by calcium carbonate($CaCO_3$) could be confirmed.

Experimental Fetal Cardiopulmonary Bypass in the Fetal Lamb Model (태아양 모델을 이용한 실험적 태아 심폐우회술)

  • 이정렬;임홍국;김원곤;김종성;최정연;김용진
    • Journal of Chest Surgery
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    • v.32 no.6
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    • pp.495-503
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    • 1999
  • Background: We tested the technical feasibility of fetal cardiac bypass and collected baseline data on the fetal hemodynamics and placental functions related to the cardiopulmonary bypass in the fetal lamb model. Material and Method: Eleven fetuses at 120 to 150 days of gestation were subjected to bypass via trans-sternal approach with a 12 G pulmonary arterial cannula and 14 to 18 F venous cannula for 30 minutes. All ewes received general anesthesia with ketamine. In all the fetuses, no anesthetic agents were used except muscle relaxant. Eight served as a group in which placenta was excluded from the extracorporeal circulation by clamping the umbilical cord during the bypass(the oxygenator group) and in the remaining three, the placenta worked as the only source of oxygen supply(the placenta group). Observations were made every 10 minute during a 30-minute bypass and 30-minute post bypass period. No prostaglandin inhibitors were used both in ewes and in fetuses. Result: Weights of the fetuses ranged from 1.9 to 5.2 kg. In the oxygenator group, means of arterial pressure, PaO2, atrial pressure, heart rate, and bypass flow rate ranged 69.8 to 82.6 mmHg, 201.7 to 220.9 mmHg, 4.1 to 4.3 mmHg, 169 to 182/min, and 140.3 to 164.0 ml/kg/min, respectively during bypass, but rapid deterioration of the fetal cardiac functions and the placental gas exchange was observed after the cessation of bypass. In the placenta group, means of arterial pressure decreased from 44.7 to 14.4 mmHg and means of PaCO2 increased from 61.9 to 129.6 mmHg during bypass. Flow rate was suboptimal(74.3 to 97.0 ml/kg/min) during bypass. All hearts fibrillated immediately after the discontinuation of bypass. Conclusion: In this study, the technical feasibility of fetal cardiopulmonary bypass was confirmed in the fetal lamb model. However, further studies with modifications of the bypass including an addition of prostaglandin inhibitor, an application of the total spinal anesthesia on the fetus, a creation of more concise bypass circuit, and a use of active pump are mandatory to improve the outcome.

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