• Title/Summary/Keyword: enzyme inhibitors

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Effect of ACE Inhibitor on Nephrotic Proteinuria in the Children (ACE inhibitor가 소아 신증후군에서 단백뇨 소실에 미치는 영향)

  • Park, Eun-Hye;Kim, Ji-Hong;Kim, Pyung-Kil
    • Childhood Kidney Diseases
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    • v.3 no.1
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    • pp.42-47
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    • 1999
  • Angiotensin-converting enzyme inhibitors lower urinary protein excretion in hypertensive and normotensive patients with renal disease. Most children with nephrotic syndrome have minimal change histology and the great majority of these patients respond to the treatment with oral prednisone. Here we have studied the effects of combination of Inhibace and oral prednisone in pediatric patients with nephrotic syndrome. 45 patients with nephrotic syndrome were selected. Of these, 29 patients were treated with prednisone(2mg/kg/day) and 16 children were treated with prednisone and Inhibace(2.5mg/day). Urinary protein, blood pressure, creatinine clearance, serum creatinine, serum albumin and serum cholesterol were measured in both control and Inhibace group. Also the duration to remission after treatment was compared in both groups. The amounts of proteinuria before and after treatment were not significantly different in both group. The duration to remission of proteinuria was significantly shorter in Inhibace group compared to that in control group. The changes of blood pressure and creatinine clearance were not significant in Inhibace group. In conclusion, the combination therapy of oral prednisone and ACE inhibitor have shortened the duration to remission of proteinuria in nephrotic syndrome of children.

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Immunomodulatory effect of captopril and local irradiation on myeloid-derived suppressor cells

  • Cho, Won Kyung;Shin, Sung-Won;Kim, Shin-Yeong;Hong, Chang-Won;Choi, Changhoon;Park, Won;Noh, Jae Myoung
    • Radiation Oncology Journal
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    • v.34 no.3
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    • pp.223-229
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    • 2016
  • Purpose: This study is to investigate the effect of captopril when combined with irradiation. Materials and Methods: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha ($HIF-1{\alpha}$) of tumor was evaluated by immunohistochemical (IHC) staining. Results: The mean tumor volumes (${\pm}$standard error) at the 15th day after randomization were $1,382.0({\pm}201.2)mm^3$ (group 1), $559.9({\pm}67.8)mm^3$ (group 3), and $370.5({\pm}48.1)mm^3$ (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and $HIF-1{\alpha}$ positivity in tumor cells were decreased when treated with captopril. Conclusion: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.

Inhibitory Effects of Fucoidan on Melanin Synthesis and Tyrosinase Activity (Fucoidan의 멜라닌 합성과 tyrosinase 활성도 억제 효과)

  • Jung, Sook-Hee;Ku, Mi-Jung;Moon, Hee-Jung;Yu, Byeng-Chul;Jeon, Man-Joong;Lee, Yong-Hwan
    • Journal of Life Science
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    • v.19 no.1
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    • pp.75-80
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    • 2009
  • Melanogenesis is a physiological process that results in the synthesis of melanin pigments. Tyrosinase is a key enzyme for melanin biosynthesis, and hyperpigmentation disorders are associated with abnormal accumulation of melanin pigments, which can be improved by treatment with depigmenting agents. Among the possible melanin-reducing compounds, tyrosinase inhibitors are most promising for preventing and treating pigmentation disorder and are used as skin-whitening agents in the cosmetic industry. In the present study, the effects of fucoidan on melanogenesis and tyrosinase activity of B16F10 melanoma cells were investigated. Melanin synthesis and tyrosinase activity in B16F10 melanoma cells were decreased in a dose-dependent manner by fucoidan. Melanin production and tyrosinase activity in B16F10 melanoma cells stimulated by a-melanocyte stimulating hormone (a-MSH) were inhibited by fucoidan with a dose-dependent manner compared to control. Fucoidan inhibited tyrosinase activity of B16F10 melanoma cells with a dose-dependent manner as assessed by 3,4-dihydroxyphenylalanine (DOPA) staining. In conclusion, these findings indicate that fucoidan, which inhibit melanin synthesis and tyrosinase activity, is an effective skin-whitening agent.

Contribution of a Low-Barrier Hydrogen Bond to Catalysis Is Not Significant in Ketosteroid Isomerase

  • Jang, Do Soo;Choi, Gildon;Cha, Hyung Jin;Shin, Sejeong;Hong, Bee Hak;Lee, Hyeong Ju;Lee, Hee Cheon;Choi, Kwan Yong
    • Molecules and Cells
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    • v.38 no.5
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    • pp.409-415
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    • 2015
  • Low-barrier hydrogen bonds (LBHBs) have been proposed to have important influences on the enormous reaction rate increases achieved by many enzymes. ${\Delta}^5$-3-ketosteroi isomerase (KSI) catalyzes the allylic isomerization of ${\Delta}^5$-3-ketosteroid to its conjugated ${\Delta}^4$-isomers at a rate that approache the diffusion limit. Tyr14, a catalytic residue of KSI, has been hypothesized to form an LBHB with the oxyanion of a dienolate steroid intermediate generated during the catalysis. The unusual chemical shift of a proton at 16.8 ppm in the nuclear magnetic resonance spectrum has been attributed to an LBHB between Tyr14 $O{\eta}$ and C3-O of equilenin an intermediate analogue, in the active site of D38N KSI. This shift in the spectrum was not observed in Y30F/Y55F/D38N and Y30F/Y55F/Y115F/D38N mutant KSIs when each mutant was complexed with equilenin, suggesting that Tyr14 could not form LBHB with the intermediate analogue in these mutant KSIs. The crystal structure of Y30F/Y55F/Y115F/D38N-equilenin complex revealed that the distance between Tyr14 $O{\eta}$ and C3-O of the bound steroi was within a direct hydrogen bond. The conversion of LBHB to an ordinary hydrogen bond in the mutant KSI reduced the binding affinity for the steroid inhibitors by a factor of 8.1-11. In addition, the absence of LBHB reduced the catalytic activity by only a factor of 1.7-2. These results suggest that the amount of stabilization energy of the reaction intermediate provided by LBHB is small compared with that provided by an ordinary hydrogen bond in KSI.

Acetylcholinesterase-based Biosensor for Detection of Residual Organophosphates and Carbamates Insecticides (유기인계 및 카바메이트계 농약을 측정할 수 있는 바이오 센서의 개발)

  • Kim, Young-Mee;Kim, Jin-Young;Cho, Moon-Jae;Chang Kong-Man;Hyun, Hae-Nam;Cho, Somi K.
    • Applied Biological Chemistry
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    • v.49 no.4
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    • pp.315-321
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    • 2006
  • Inhibitors of acetylcholinesterase(AchE), such as organophosphates and carbamates, interfere the action of AchE in nerve and may lead to a severe impairment of nerve functions or even death. Therefore, insect AchE is the biological target of predominant insecticides used in agriculture. Biosensors are sensitive and can be used as dispoisable sensors for environmental control. In recent years, the use of AchEs in biosensor technology has gained enormous attention, in particular with respect to insecticide detection. The principle of biosensors using AchE as a biological recognition element is based on the inhibition the catalytic activity by the agents to be detected. We here present a strip-type biosensor based on AchE inhibition. In this study, acetylcholinesterase and PVA-SbQ(polyvinyl alcohol functionalized with methyl pyridinium methyl sulfate) were co-immobilized on immobilone-P membranes. Immobilization of the enzymes showed a stability in 6 months without activity loss in $4^{\circ}C$ storage. Enzymes immobilized on surfaces of membrane responded to organophosphates and carbamate more sensitivitive than enzyme in solution. Organophosphates and carbamates concentrations could be detected by entrapped and surface immobilized enzymes, in 5 min. For chlorpyrifos, carbofuran, cabaryl, and methidathion, the detection limits of AChE-strip were similar to that of HPLC/GC method.

Physician Factors Associated with the Blood Pressure Control among Hypertensive Patients (진료를 받는 고혈압 환자의 혈압 조절과 관련된 의사 요인)

  • Kim, So-Young;Cho, In-Sook;Lee, Jae-Ho;Kim, Ji-Hyun;Lee, Eun-Jung;Park, Jong-Hyock;Lee, Jin-Seok;Kim, Yoon
    • Journal of Preventive Medicine and Public Health
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    • v.40 no.6
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    • pp.487-494
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    • 2007
  • Objectives : Little is known about the physician-related factors that are associated with the management of Hypertension. The purpose of this study was to determine the physician-related factors associated with blood pressure control in hypertensive patients. Methods : We surveyed 154 physicians at 117 public health (subhealth) centers in Gyeonggi-do, Forty-one physicians completed the survey (response rates : 26.6%) and 31 physicians were finally included as the study subjects. Using the information obtained from the self-reported survey, we measured the physician-related factors associated with hypertension control, including their perception of hypertension, prescription patterns (combination prescription rates, specific antihypertensives prescription rates among patients with diabetes mellitus), and sociodemographic factors. We then collected data on blood pressure and medication use in patients seen by these physicians from the health center#s information system. We compared the physicians# perceived hypertension control rates with the actual rates, and then evaluated the rate of high overestimation (overestimation by more than 25% of the median degree of hypertension control rate overestimation) among the physicians. The physicians# antihypertensive prescription patterns were also evaluated. Multiple logistic regression analysis was used to evaluate the independent association between hypertension control and physician-related factors. Results : The physicians tended to overestimate the proportion of their patients with controlled blood pressure (79.5% perceived vs. 57.8% actual). The percentage of physicians with high overestimation was 35.5% (11 physicians). The physicians with lower control rates were more likely to highly overestimate their patients# control rates. Physicians with below-median actual control rates tended to prescribe fewer combination treatments for patients with uncontrolled blood pressure and angiotensin-converting enzyme inhibitors or fewer angiotensin receptor blockers for patients with diabetes mellitus. The rate of high overestimation by physicians was 1.31 times higher in patients with uncontrolled blood pressure than in patients with other conditions (OR=1.31, 95% CI : 1.17-1.48). Conclusions : Physicians have a tendency to overestimate the rates of hypertension control in their patients. Because physicians have a direct role in treatment outcomes, physicians# overestimation about hypertension management contributes to inadequate blood pressure control. Thus, interventions for improving physician# awareness regarding the management of patients with hypertension are needed.

Microsomal Proton Transport Activity Measured by Quinacrine Fluorescence from Tomato Roots (Quinacrine 형광을 이용한 토마토 뿌리조직 마이크로솜의 수소이온이동 활성측정)

  • Shin, Dae-Seop;Cho, Kwang-Hyun;Kim, Young-Kee
    • Applied Biological Chemistry
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    • v.45 no.2
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    • pp.53-58
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    • 2002
  • Quinacrine, a pH-sensitive fluorescence probe, which exists either as an unprotonated fluorescence form or a protonated noufluorescence form, can be used to measure the proton transport activity of $H^+-ATPase$. Quinacrine was used to determine the optimal conditions for measuring the activity of microsomal $H^+-ATPase$ prepared from the roots of tomato plants. The amount of quinacrine fluorescence quenching obtained at $0.43{\mu}g/{\mu}l$ of microsomal protein concentration was 25-26%, which shows that the enzyme activity of 100 nmol/min decreases 10% of quinacrine fluorescence. Maximal fluorescence quenching was obtained at pH 7.0-7.2 and 2 mM $Mg^{2+}$ Because the activity of microsomal $H^+-ATPase$ is also maximal at these conditions, the quinacrine fluorescence well represents the activity of $H^+-ATPase$. Vanadate and $NO_3-$, specific inhibitors of plasma and vacuolar $H^+-ATPases$, respectively, were successfully applied to inhibit the quinacrine fluorescence quenching mediated by the corresponding $H^+-ATPases$. These results imply that quinacrine is a useful tool for measuring the proton transport activities of microsomes obtained from the root tissue of tomato plants.

PHENOLOXIDASE AND ANTIOXIDANT IN KOREAN GINSENG (고려인삼에 있어서의 페놀 산화효소의 항산화물질)

  • Park E.Y.;Luh B.S.;Branen A.L.
    • Proceedings of the Ginseng society Conference
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    • 1984.09a
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    • pp.257-275
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    • 1984
  • Enzymatic browning is considered desirable in tea and tobacco processing but undesirable in many fruits processing at the present time. It is necessary to understand the nature of the enzyme, phenoloxidase, in order to control browning reactions, and extend its effects to formation of browning products as antioxidants in ginseng. Ginseng exhibits antioxidant activity when incorporated with turkey dark meat patties. The activity in red ginseng showed about two times stronger than white ginseng. One of the phenolic antioxidants from fresh, white and reprocessed white ginseng was identified as phenol 2.6 Bis(1.1 dimethyl ethyl) 4-methyl among several unknown compounds by GC/mass spectrometer. In red ginseng, no phenol 2.6 Bis (1.1 dimethyl ethyl) 4-methyl was detected, the compound may be polymerized by phenoloxidase and form some higher molecular compounds which may possess high antioxidant activity. Phenoloxidase isozymes in fresh Korean ginseng (panax ginseng C.A. Meyer) were extracted with phosphate buffer at pH 7.3. The isozymes were purified through ammonium sulfate fractionation, dialysis and chromatography on a DEAE-cellulose column. Two groups of phenoloxidase were shown to be present, one in the floating agglomerated group and the other in the precipitate. group from the 0.85 saturation ammonium sulfate. The DEAE-cellulose column chromatography, the phenoloxidase isozyme present in the precipitate appears as the first peak (I), and that in the agglomerate in the second peak (II). Isozyme I showed higher activity with catechin and catechal, and isozyme II showed higher activity with p-cresol. The isozyme showed two optimum pH activity one at pH 4.5 and the other at 8.5 with catechin as substrate. Korean ginseng phenoloxidase has high heat stability. When heated at $75^{\circ}C$ for 2 hours, its activity remained $90\%\;and\;80\%$ on phenoloxidase I and II respectively. Phenoloxidase I was most active on (+) catechin followed by p-cresal, catechol and epicatechin. Phenoloxidase II was most active on p-cresal followed by (+) catechin, catechol, p-coumanic acid and epicatechin. Sodium bisulfite, sodium cyanide, ascorbic acid glutachion in the oxidized form, sodium diethyl dithiocarbomate and ethylendiamine tetra acetate (EDTA) acted as inhibitors. Red ginseng color development was initiated by phenoloxidase and finished by a followed sun drying process. The antiaging activity of ginseng may be initiated by the antioxidant in the ginseng.

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Studies on Inhibition of Self-Incompatibility with Micronutrients in Apple (미량요소 첨가가 자가불화합성 억제에 미치는 영향)

  • Chung, Il-Kyung;Son, Tae-Kwon;Kim, Min-Ji
    • Korean Journal of Plant Resources
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    • v.25 no.2
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    • pp.285-292
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    • 2012
  • Self-incompatibility (SI) system is a genetic barrier that prevents self-fertilization and promotes cross-pollination among different S genotypes. In many of these species, SI is controlled by a single genetic locus known as S locus, which prevents the fertilization by pollen with same locus. S RNases are the products of the S-locus expressed in the stylar tissue of Fuji Apple with gametophytic self-incompatibility system. This study investigated the various types of chemicals in order to select more effective inhibitors and activators. The effect on the inhibition of S RNase of Fuji apples was investigated $in$ $vitro$. The result showed that the enzyme activity was reduced 24.3% by Iron(II) Sulfate, significantly. $In$ $vitro$ studies of pollen growth tube showed that pollen tube growth had a higher germination rate (90%) in 10% Sucrose than in 2% sucrose extension medium. Data on the fruit set of apples treated with inhibitor and activator. Double application of $A^+$(Apple Plus, ISTECH Co. Ltd.,)+Vitamin B6 had the highest central fruit set as 86.1%(Andong). One time application of $A^{++}$Vitamin B1 in Yeongju obtained the highest central fruit set (91.9%).

Effects of phenylephrine-induced PKC activation on Mg2+ release in guinea pig heart and isolated ventricular myocytes (기니픽 심장과 심근세포에서 Phenylephrine에 의한 PKC 활성화가 Mg2+ 유리에 미치는 영향)

  • Chang, Sung-eun;Kang, Hyung-sub;Kim, Jin-sang
    • Korean Journal of Veterinary Research
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    • v.38 no.1
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    • pp.29-42
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    • 1998
  • $Mg^{2+}$ is one of the most abundant divalent cations in mammalian body(0.2~1.0mM) and the important physiological roles are : first, the cofactor of many enzyme activities, second, the regulator of glycolysis and DNA synthesis, third, the important role of bioenergetics by regulating of phosphorylation, fourth, the influence of cardiac metabolism and function. In this work we have investigated the regulation of the $Mg^{2+}$ induced by ${\alpha}_1-adrenoceptor$ stimulation in perfused guinea pig hearts and isolated myocytes. The $Mg^{2+}$ content of the perfusate or the supernatant was measured by atomic absorbance spectrophotometry. The elimination of $Mg^{2+}$ in the medium increased the force of contraction of right ventricular papillary muscles, and the left ventricular pressure. Phenylephrine also enhanced the force of contraction in the presence of $Mg^{2+}-free$ medium. ${\alpha}_1-Agonists$ such as phenylephrine and methoxamine were found to induce $Mg^{2+}$ efflux in both perfused hearts and myocytes. These effects were blocked by prazosin, an ${\alpha}_1-adrenoceptor$ antagonist. The $Mg^{2+}$ influx could also be induced by phenylephrine and R59022, a diacylglycerol kinase inhibitor. In the presence of protein kinase C(PKC) inhibitors, phenylephrine produced an increase in $Mg^{2+}$ efflux from perfused hearts. Furthermore, $Mg^{2+}$ efflux by phenylephrine was amplified by phorbol 12-myristate 13-acetate(PMA). This enhancement of $Mg^{2+}$ efflux by PMA was blocked by prazosin in perfused hearts. By contrast, the $Mg^{2+}$ influx could be induced by verapamil, nifedipine, ryanodine in perfused hearts, but not in myocytes. $W^7$, a $Ca^{2+}$/calmodulin antagonist, completely blocked the phenylephrine-induced $Mg^{2+}$ efflux in perfused hearts. In conclusion, $Mg^{2+}$ is responsible for the cardiac activity associated with ${\alpha}_1-adrenoceptor$ stimulation. The mobilization of $Mg^{2+}$ is decreased or increased by ${\alpha}_1-adrenoceptor$ stimulation in guinea pig hearts. These responses may be related specifically to the respective pathways of signal transduction. A decrease in $Mg^{2+}$ efflux by ${\alpha}_1-adrenoceptor$ stimulation in hearts can be through PKC dependent and intracellular $Ca^{2+}$ levels.

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