• Title/Summary/Keyword: Plasma enzyme

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Detecting Activated Thrombin Activatable Fibrinolysis Inhibitor (TAFIa) and Inactivated TAFIa (TAFIai) in Normal and Hemophilia A Plasmas

  • Hulme, John P.;An, Seong Soo A.
    • Bulletin of the Korean Chemical Society
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    • v.30 no.1
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    • pp.77-82
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    • 2009
  • Thrombin activatable fibrinolysis inhibitor (TAFI) also known as plasma procarboxypeptidase B or U is a 60 kD glycoprotein, which is the major modulator of fibrinolysis in plasma. TAFI is a proenzyme, which is activated by proteolytic cleavage to an active carboxypeptidase B-like enzyme (TAFIa, 35.8 kD) by thrombin/thrombomodulin and plasmin. Modulation of fibrinolysis occurs when TAFIa enzymatically removes C-terminal lysine residues of partially degraded fibrin, thereby inhibiting the stimulation of tissue plasminogen activator (t-PA) modulated plasminogen activation. TAFIa undergoes a rapid conformational change at $37{^{\circ}C}$ to an inactive isoform called TAFIai. Potato tuber carboxypetidase inhibitor (PTCI) was shown to specifically bind to TAFIa as well as TAFIai. In this study, a novel immunoassay TAFIa/ai ELISA was used for quantitation of the two TAFI activation isoforms TAFIa and TAFIai. The ELISA utilizes PTCI as the capture agent and a double antibody sandwich technique for the detection. Low levels of TAFIa/ai antigen levels were detected in normal plasma and elevated levels were found in hemophilia A plasmas. TAFIa/ai antigen represents a novel marker to monitor fibrinolysis and TAFIa/ai ELISA may be a valuable assay for studying the role of TAFI in normal hemostasis and in pathological conditions.

Enhanced Nimodipine Bioavailability After Oral Administration of Nimodipine with Morin, a Flavonoid, in Rabbits

  • Choi Jun-Shik;Burm Jin-Pil
    • Archives of Pharmacal Research
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    • v.29 no.4
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    • pp.333-338
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    • 2006
  • The aim of this study was to investigate the effect of morin on the bioavailability of nimodipine after administering nimodipine (15 mg/kg) orally to rabbits either co-administered or pretreated with morin (2, 10 and 20 mg/kg). The plasma concentrations of nimodipine in the rabbits pretreated with morin were increased significantly (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg) compared with the control, but the plasma concentrations of nimodipine co-administered with morin were not significant. The areas under the plasma concentration-time curve (AUC) and the peak concentrations $(C_{max})$ of the nimodipine in the rabbits pretreated with morin were significantly higher (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg), but only the $C_{max}$ of nimodipine coadministered with morin 10 mg/kg was increased significantly (p<0.05). The absolute bioavailability $(A.B\%)$ of nimodipine in the rabbits pretreated with morin was significantly (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg) higher $(54.1-65.0\%)$ than the control $(36.7\%)$. The increased bioavailability of nimodipine in the rabbits pretreated with morin might have been resulted from the morin, which inhibits the efflux pump P-glycoprotein and the first-pass metabolizing enzyme by cytochrome P-450 3A4 (CYP 3A4).

Action of Extracellular Protease of Aspergillus terreus on Human Plasma Hemostasis Proteins

  • Alexander A. Osmolovskiy;Elena S. Zvonareva;Nina A. Baranova;Valeriana G. Kreyer
    • Microbiology and Biotechnology Letters
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    • v.51 no.2
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    • pp.167-173
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    • 2023
  • Proteolytic enzymes secreted by Aspergillus, as pathogenicity factors, affect blood coagulation and fibrinolysis, and therefore the target proteins of their action in the bloodstream are of significant interest. In the present study, the action of the isolated protease of A. terreus 2 on different human plasma proteins was shown. The protease of A. terreus 2 exhibited the highest proteolytic activity against hemoglobin, which was 2.5 times higher than the albuminolytic activity shown in both of the protein substrates used. In addition, the protease has significant ability to hydrolyze both fibrin and fibrinogen. However, the inability of the A. terreus 2 protease to coagulate rabbit blood plasma and coagulate human and bovine fibrinogen indicates the severity of the enzyme's action on human blood coagulation factors. It should be considered as a potential indicator of this isolated protease's participation in fungal pathogenesis. The protease shows no hemolytic activity. Furthermore, its activity is insignificantly inhibited by thrombin inhibitors, and is not inhibited by plasmin inhibitors.

$Na^+-K^+$ ATPase: Regulation by Signal Transduction Pathways in Cardiac Myocytes

  • Lee, Chin-Ok
    • Proceedings of the Korean Biophysical Society Conference
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    • 2002.06b
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    • pp.9-11
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    • 2002
  • Plasma membrane Na$^{+}$-K$^{+}$ ATPase (pump) is an essential component to maintain asymmetrical ion distribution across cell membrane. The Na$^{+}$-K$^{+}$ ATPase was discovered by Jens C. Skou in 1957 and since then physiological and biochemical properties of the enzyme have been extensively studied. Jens C. Skou was awarded the 1997 Nobel Prize in chemistry for his discovery of the Na $^{+}$ - $K^{+}$ ATPase.(omitted)

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Effect of Different Part of Mandarin Intake on Antioxidative Capacity in 15-month-old Rats (감귤의 부위별 섭취가 노령흰쥐의 항산화능에 미치는 영향)

  • 김지혜;김미경
    • Journal of Nutrition and Health
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    • v.36 no.6
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    • pp.559-569
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    • 2003
  • This study was performed to investigate the effect of whole mandarin, peel, and pulp intake of Citrus unshiu Marc on the antioxidative capacity of 15-month-old rats. Forty-eight male Sprague-Dawley rats weighing 621.9 $\pm$ 10.1 g were separated into four groups according to body weight. The rats were raised with diets containing 5% (w/w) dried mandarin powder for four weeks. Three powders were used, consisting of mandarin peel, pulp, and the entire fruit. Total flavonoids, antioxidant vitamins and dietary fiber was highest in the mandarin peel powder, followed by the whole mandarin powder and the mandarin pulp. The body weight gains of the whole mandarin and mandarin pulp groups were higher, while that of the mandarin peel group was lower than that of the control group. Food intake and ratios of liver, kidney and epididymal fat pad (EFP) weights to body weight were not significantly different among the groups, but ratios of EFP weights per body weight of the experimental groups tended to be lower than that of the control animals. Plasma and liver TBARS concentrations decreased in all the mandarin groups compared to the control group. Plasma and liver xanthine oxidase (XO) activity decreased in all of the mandarin diet groups. Erythrocyte and liver SOD activity in all of experimental groups was not significantly different from the control group. Plasma vitamin A concentration increased significantly in all of the mandarin diet groups. That of the mandarin peel group was 4 times higher than that of the control group. Plasma total carotenoids and vitamin C level also increased in the mandarin peel group. Plasma vitamin I level was not significantly different among the groups.

Red beet(Beta vulgaris L.) leaf supplementation improves antioxidant status in C57BL/6J mice fed high fat high cholesterol diet

  • Lee, Jeung-Hee;Son, Chan-Wook;Kim, Mi-Yeon;Kim, Min-Hee;Kim, Hye-Ran;Kwak, Eun-Shil;Kim, Se-Na;Kim, Mee-Ree
    • Nutrition Research and Practice
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    • v.3 no.2
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    • pp.114-121
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    • 2009
  • The effect of diet supplemented with red beet (Beta vulgaris L.) leaf on antioxidant status of plasma and tissue was investigated in C57BL/6J mice. The mice were randomly divided into two groups after one-week acclimation, and fed a high fat (20%) and high cholesterol (1%) diet without (control group) or with 8% freeze-dried red beet leaf (RBL group) for 4 weeks. In RBL mice, lipid peroxidation determined as 2-thiobarbituric acid-reactive substances (TBARS value) was significantly reduced in the plasma and selected organs (liver, heart, and kidney). Levels of antioxidants (glutathione and $\beta$-carotene) and the activities of antioxidant enzyme (glutathione peroxidase) in plasma and liver were considerably increased, suggesting that antioxidant defenses were improved by RBL diet. Comet parameters such as tail DNA (%), tail extent moment, olive tail moment and tail length were significantly reduced by 25.1%, 49.4%, 35.4%, and 23.7%, respectively, in plasma lymphocyte DNA of RBL mice compared with control mice, and indicated the increased resistance of lymphocyte DNA to oxidative damage. In addition, the RBL diet controlled body weight together with a significant reduction of fat pad (retroperitoneal, epididymal, inguinal fat, and total fat). Therefore, the present study suggested that the supplementation of 8% red beet leaf in high fat high cholesterol diet could prevent lipid peroxidation and improve antioxidant defense system in the plasma and tissue of C57BL/6J mice.

Identification of surface antigen of Trichomonas vaginalis (질편모충의 표면항원 분석)

  • 민득영;임미혜
    • Parasites, Hosts and Diseases
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    • v.32 no.4
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    • pp.243-248
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    • 1994
  • Plasma membrane proteins of a Korean isolate of Trichomonus vofinalis HY-1 were fractionated for antigen analysis. Homogenates of T. vaginalis were fractionated by the differential centrifugation using sucrose step-gradient method. The interface layer from the 25%/45% sucrose was collected as a plasma membrane fraction and its purity was examined by transmission electron microscopy. The antigenicity of plasma membrane fraction was analysed by enzyme-linked immunoelectrotransfer blot technique with immune rabbit serum and compared with surface antigen labelled with N. hydroxysuccinimide-biotin. The fluffy fraction of 25%/45% sucrose interface was homogeneous and membrane particles were present as extended sheet and concentric vesicles showing typical trilamellar appearance under transmission electron microscope. Seven fractions at 40, 50, 60, 110, 130, 140 and 150 kDa were identified as the antigenic membrane proteins in EITB with anti HY-1 rabbit serum. The common band at 60 kDa was detected both in antigenic fractions of plasma membrane and surface protein labelled with NHS-biotin. This result indicates that this protein is considered as a major surface antigen of T. vaginalis. The role of this surface antigen at 60 kDa should be studied further.

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Pharmacokinetics and Tissue Distribution of Recombinant Human Erythropoietin (DA-3285) in the Laboratory Animals (Recombinant human erythropoietin (DA-3285)의 실험동물에서의 약동력학 및 조직분포)

  • 심현주;이응두;이종진;김흥재;이상득;이성희;김원배;양중익
    • Biomolecules & Therapeutics
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    • v.4 no.1
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    • pp.78-83
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    • 1996
  • The pharmacokinetics and tissue distribution of DA-3285 (recombinant human erythropoietin, recently manufactured by Research Laboratories of Dong-A Pharmaceutical Company) were studied in the laboratory animals. The plasma, urine, and tissue concentration of DA-3285 were measured by a double-antibody sandwich enzyme immunoassay. After intravenous administration of DA-3285, 20, 100, 500 and 2500 units/kg to rats, the plasma concentrations declined polyexponentially with the terminal half-lives of 2.15, 2.10, 2.31, and 2.35 hr, respectively. Total body clearance (20.7∼26.6 mι/hr/kg) and apparent volume of distribution at steady state (57.2∼70.1 mι/kg) were independent of the dose and AUC increased proportionally with the dose. The renal clearance was much lower than total body clearance, suggesting that extrarenal clearance, presumably metabolism , plays a significant role in elimination of DA-3285. In all rat tissues, the tissue to plasma ratios were smaller than unity, indicating less affinity of DA-3285 to rat tissues and was proved by considerably less value of Vdss. After 3 times a week for consecutive 3 weeks i.v. administration of DA-3285, 100 units/kg to rats, the plasma concentrations and pharmacokinetic parameters of DA-3285 were not significantly different from those in a single administration. After s.c. administration to the rat, plasma concentrations of DA-3285 peaked at 6 hr and the extent of bioavailability was 26.7%. In mice, rabbits and dogs, at DA-3285 dose of 100 units/kg, the mean terminal haw-lives were 2.78, 3.05, and 4.01 hr, respectively. Compared with reported data in the literatures, DA-3285 has similar properties to rh-EPO manufactured by other companies in view of pharmacokinetics.

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Effects of SULT1A1 Copy Number Variation on Estrogen Concentration and Tamoxifen-Associated Adverse Drug Reactions in Premenopausal Thai Breast Cancer Patients: A Preliminary Study

  • Charoenchokthavee, Wanaporn;Ayudhya, Duangchit Panomvana Na;Sriuranpong, Virote;Areepium, Nutthada
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1851-1855
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    • 2016
  • Tamoxifen is a pharmacological estrogen inhibitor that binds to the estrogen receptor (ER) in breast cells. However, it shows an estrogenic effect in other organs, which causes adverse drug reactions (ADRs). The sulfotransferase 1A1 (SULT1A1) enzyme encoded by the SULT1A1 gene is involved in estrogen metabolism. Previous research has suggested that the SULT1A1 copy number is linked with the plasma estradiol (E2) concentration. Here, a total of 34 premenopausal breast cancer patients, selected from the Thai Tamoxifen (TTAM) Project, were screened for their SULT1A1 copy number, plasma E2 concentration and ADRs. The mean age was $44.3{\pm}11.1years$, and they were subtyped as ER+/progesterone receptor (PR)+ (28 patients), ER+/PR- (5 patients) and ER-/PR- (1 patient). Three patients reported ADRs, which were irregular menstruation (2 patients) and vaginal discharge (1 patient). Most (33) patients had two SULT1A1 copies, with one patient having three copies. The median plasma E2 concentration was 1,575.6 (IQR 865.4) pg/ml. Patients with ADRs had significantly higher plasma E2 concentrations than those patients without ADRs (p = 0.014). The plasma E2 concentration was numerically higher in the patient with three SULT1A1 copies, but this lacked statistical significance.

Systemic Expression of Vascular Endothelial Growth Factor in Patients with Cerebral Cavernous Malformation Treated by Stereotactic Radiosurgery

  • Park, Sang-Jin;Park, Seong-Hyun
    • Journal of Korean Neurosurgical Society
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    • v.59 no.5
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    • pp.442-448
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    • 2016
  • Objective : Increased expression of angiogenic factors, such as vascular endothelial growth factor (VEGF), is associated with the pathogenesis of cerebral cavernous malformations (CCMs). The purpose of this study was to investigate plasma levels of VEGF in normal subjects and in patients with CCM and to evaluate change in these levels following stereotactic radiosurgery (SRS). Methods : Peripheral venous blood was collected from 6 patients with CCM before SRS using Gamma Knife and at the 1 week, 1 month, 3month, and 6 month follow-up visits. Plasma VEGF levels were measured using commercially available enzyme-linked immunosorbent assay kits. Peripheral blood samples were obtained from 10 healthy volunteers as controls. Results : Mean plasma VEGF level of 41.9 pg/mL (range, 11.7-114.9 pg/mL) in patients with CCM at baseline was higher than that of the healthy controls (29.3 pg/mL, range, 9.2-64.3 pg/mL), without significant differences between CCM patients and controls (p=0.828). Plasma VEGF level following SRS dropped to 24.6 pg/mL after 1 week, and decreased to 18.5 pg/mL after 1 month, then increased to 24.3 pg/mL after 3 months, and 32.6 pg/mL after 6 months. Two patients suffering from rebleeding after SRS showed a higher level of VEGF at 6 months after SRS than their pretreatment level. Conclusion : Plasma VEGF levels in patients with CCM were elevated over controls at baseline, and decreased from baseline to 1 month after SRS and increased further for up to 6 months. Theses results indicated that anti-angiogenic effect of SRS might play a role in the treatment of CCMs.