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  • 1
    ISSN: 1432-1041
    Keywords: Leukotiene D4 ; L-648,051 ; LTD4-antagonist ; SRS-A ; Pharmacokinetics ; tolerability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Two formulations of L-648,051 (L) were studied [intravenous (i.v.) and aerosol (A)] in two separate trials. Study I (i.v.) involved 4 normal male subjects in a single blind dose ranging study where good systemic tolerability and safety was shown. However, dose dependent local irritation at the injection site was observed at all dose levels (35, 52.5 and 70 mg/5 min infusion). L has a high systemic clearance rate (1.2 l/min), a small volume of distribution (4.4 l) and a short plasma half-life (2.4 min). Study II (A) involved 16 normal male volunteers who received incremental aerosolized doses of L from 0.1 to 1.6 mg in a double-blind, placebo controlled, dose ranging study. Complaints of mild local irritation or discomfort in the upper respiratory tract were the only significant findings. No dose relationship of these complaints could be shown. In conclusion, L is a safe and well tolerated drug when administered by aerosol. It causes dose related local, but not systemic, adverse experiences when administered i.v. In view of this tolerability and of its demonstrated activity against LTD4-challenge in animals, clinical efficacy studies with the aerosol formulation are warranted.
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  • 2
    ISSN: 1432-1041
    Keywords: MK-571 ; LTD4 receptor antagonist ; tolerability ; plasma profiles ; enantiomer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the tolerability and plasma drug profiles of a leukotriene D4 receptor antagonist, MK-571, given intravenously and as an oral solution in two separate trials. Study I (i.v.) involved 2 panels of 6 healthy men in a double-blind, alternating, incrementally increasing dose study with single doses up to 1500 mg. There was good tolerability at all doses. Plasma was assayed stereospecifically by HPLC for the S(+) and R(−) enantiomers of MK-571. For each enantiomer AUC values increased more than proportionately with increasing dose, suggesting nonlinear kinetics. The S(+) enantiomer was cleared more rapidly than the R(−) enantiomer. The apparent initial volume of distribution was less than 101 for both enantiomers. Study II (oral) involved 18 healthy subjects in 3 parallel groups who took multiple oral doses of 100, 300, and 600 mg t. i. d. for 31 doses. MK-571 administration was well tolerated, with only mild to moderate gastrointestinal discomfort at the highest dose. Total MK-571 (plasma samples assayed nonstereoselectively) was rapidly absorbed after oral administration, reaching peak concentrations at 1–2 h. Mean 8 h AUC increased from dose 1 to dose 31 in all subjects at all doses, suggesting a modest extent of accumulation (about 50 %) of total MK-571 in plasma with a t. i. d. dosage regimen.
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  • 3
    ISSN: 1432-1041
    Keywords: MK-571, LTD4-receptor antagonist ; MK-0679, L-668,018, pharmacokinetics, enantiomers, healthy volunteers, pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of the enantiomers of MK-571 (MK-0679 and L-668,018) following single i. v. doses of MK-571 (L-660,711) was studied in a three way cross-over study in 12 healthy male volunteers. Each volunteer received 75 mg, 300 mg and 600 mg i. v. doses of MK-571 at weekly intervals. The disposition of both enantiomers appeared dose-dependent, since the AUC increased disproportionately faster than the dose. The dose dependency was much more pronounced for L-668,018: its AUC increased 6-fold from the 75 to the 300 mg dose, 16-fold from 75 to 600 mg and 2.7 fold from 300 to 600 mg. For MK-0679, the corresponding increases in AUC were 4.8-, ll-, and 2.3 fold. Regardless of dose, the elimination of L-668,018 was more rapid than that of MK-0679. The disposition of MK-0679 needs to be investigated independently to detect any potential influence of L-668,018 on its disposition.
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  • 4
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: In order to fast and economically purify MTGase from Streptoverticillium ladakanum, a stepwise elution method was developed and compared with linear gradient elution method. MTGase was purified to electrophoretical homogeneity by using CM Sepharose CL-6B and Blue Sepharose Fast Flow chromatographies by linear gradient or stepwise methods. The recovery of MTGase by linear gradient and stepwise methods were 68.4% and 81.0%, respectively. The optimal temperature and pH were 40 °C and 5.5, respectively. It was stable at pH 5.0 to 7.0 and had a rate constant (KD) of 6.21 °o 10-5 min-1 for thermal inactivation at 45 °C. The purified MTGase was activated by K+ Na+, Ca2+, Mn2+, and Mg2+, not affected by Fe3+, EDTA, but inhibited by Cu2+, Zn2+, Hg2+, Ni2+, Co2+, Cd2+, PCMB, NEM, IAA, and PMSF. A simple stepwise method was developed for the purification of MTGase from S. ladakanum.
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of food science 67 (2002), S. 0 
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: : Effects of microbial transglutaminase (MTGase), recombinant cystatin, or their combination on the gel properties of mackerel surimi were investigated. The addition of MTGase caused the cross-linking of myosin heavy chain (MHC) and substantially increased the gel strength (from 536.6 to 2012.4 g × cm), while the recombinant cystatin could effectively prevent the MHC degradation and gel softening during the production of mackerel surimi-based products. Combined use of MTGase and recombinant cystatin revealed synergistic effectiveness on improving the quality of mackerel surimi (increased from 435 to 2438 g × cm, set at 45 °C for 20 min).
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of food science 65 (2000), S. 0 
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: : The properties of surimi gels from threadfin-bream and pollack surimi set at 30 °C or 45 °C with microbial transglutaminase (MTGase) from Streptoverticillium ladakanum were determined. The optimal amounts of MTGase and setting conditions were: 0.3 unit/g surimi either at 30 °C for 90 min or at 45 °C for 20 min for threadfin-bream, and 0.2 unit/g surimi at 30 °C for 60 min for pollack. The strength of golden threadfin-bream surimi gels with 0.35 unit MTGase set at 30 °C for 90 min or 45 °C for 20 min was 3400 g cm, almost 3-fold of the control. SDS-PAGE analyses indicated that inter- and/or intramolecular cross-linking formed in the myosin heavy chain of MTGase-containing surimi gels.
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of food science 67 (2002), S. 0 
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: : Effects of nicotinamide dinucleotide phosphate (NADPH)-sulfite reductase, recombinant cystatin, and microbial transglutaminase (MTGase) or their combination on hairtail surimi quality were investigated. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that adding NADPH-sulfite reductase could effectively recover native myosin. Apparent cross-linking of hairtail myosin during the setting process was observed with added MTGase, while myosin degradation on the heating process was substantially retarded with recombinant chicken cystatin. The combined use of NADPH-sulfite reductase, recombinant chicken cystatin, and MTGase exhibited a greater effect on improving hairtail surimi quality.
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of food science 67 (2002), S. 0 
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: : Pork sticks were prepared by mixing pork chucks with various amounts of bisulfite-treated soy protein and microbial transglutaminase (MTGase) to evaluate the potential of using soy protein as meat binders. According to tensile strength, the favorable conditions for binding the restructured pork chunks were 5% soy protein containing 0.2% NaHSO3 and 20 unit MTGase/g, and the setting condition was 60 min at 40°C. The tensile strength and cooking yield of restructured pork sticks made with bisulfite-treated soy protein and MTGase were much higher than those of using salt, suggesting the high potential of using soy protein and MTGase as binders in products where NaCl reduction is desired.
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of food science 65 (2000), S. 0 
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A combination of microbial transglutaminase (MTGase), reducing agent and protease inhibitor was employed to improve the quality of underutilized fish surimi. SDS-PAGE indicated that cross-linking of myosin heavy chain (MHC) occurred in MTGase-contained samples, while MHC of samples without MTGase disappeared after 120 min incubation at 45°C. Although the gel-forming ability increased with MTGase added up to 0.6 unit/g, it was still too low to be commercially acceptable. However, the combined use of 0.1% NaHSO3, 0.01 mM transepoxysuccinyl-L-leucylamido-(4-guanidino)butane (E-64) and 0.35 units MTGase/g substantially improved the quality of hairtail surimi. Based on this result, the combined use of E-64, MTGase and NaHSO3 seemed to be a better way to improve gel-forming ability of hairtail surimi.
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  • 10
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 162 (1989), S. 1147-1154 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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