![]() |
CiteULike |
![]() |
HEIRS's CiteULike |
![]() |
![]() |
|
![]() |
Register | ![]() |
Log in | ![]() |
Glutathione reductase is inhibited by acetaminophen-glutathione conjugate in vitro. Export |
Reviews
[Write a review of this article]
There are no reviews of this article
Find related articles from these CiteULike users
Find related articles with these CiteULike tags
Posting History
AbstractThe aim of the present work was to investigate a new mechanism likely contributing to the toxic action of acetaminophen especially to explore the possible inhibition of glutathione reductase through an acetaminophen-glutathione conjugate (APAP-SG). APAP-SG conjugate was synthesized by organic synthesis and purified by column chromatography. The inhibitory effect of the conjugate on two types of glutathione reductase (from yeasts and rat hepatocytes) was tested spectrophotometrically. We found that the enzyme activity was reduced similarly after treatment with 2.96 mM acetaminophen-glutathione conjugate in both yeast and hepatocyte glutathione reductases (GR); the enzyme activity was inhibited to 52.7 +/- 1.5 % (2.4 +/- 0.3 mU/ml) in yeast GR (control activity was 5.6 +/- 0.3 mU/ml) and to 48.1 +/- 8.8 % (2.2 +/- 0.2 mU/ml) in rat hepatocytes lysate GR (control activity was 5.2 +/- 0.2 mU/ml). In addition, the enzyme activity (from hepatocytes lysate) was decreased to 79+/-7 %, 67+/-2 % and 39+/-7 %, in 0.37, 1.48 and 3.7 mM concentration of the conjugate, respectively. We found that glutathione reductase, the essential enzyme of the antioxidant system, was dose-dependently inhibited by the product of acetaminophen metabolism - the conjugate of acetaminophen and glutathione.
BibTeX record
RIS record| 184 | |
| 150 | |
| 145 | |
| 140 | |
| 104 | |
| 100 | |
| 90 | |
| 88 | |
| 70 | |
| 62 | |
| 60 | |
| 58 | |
| 58 | |
| 57 | |
| 56 | |
| 56 | |
| 56 | |
| 54 | |
| 54 | |
| 53 | |
| 53 | |
| 53 | |
| 52 | |
| 49 | |
| 47 | |
| 45 | |
| 45 | |
| 44 | |
| 44 | |
| 43 | |
| 40 | |
| 40 | |
| 39 | |
| 38 | |
| 38 | |
| 37 | |
| 37 | |
| 36 | |
| 36 | |
| 36 | |
| 35 | |
| 35 | |
| 34 | |
| 33 | |
| 33 | |
| 32 | |
| 32 | |
| 31 | |
| 31 | |
| 30 | |
| 30 | |
| 29 | |
| 29 | |
| 29 | |
| 29 | |
| 29 | |
| 29 | |
| 28 | |
| 27 | |
| 27 | |
| 26 | |
| 25 | |
| 25 | |
| 25 | |
| 25 | |
| 24 | |
| 24 | |
| 24 | |
| 23 | |
| 22 | |
| 22 | |
| 22 | |
| 22 | |
| 22 | |
| 21 | |
| 21 | |
| 21 | |
| 21 | |
| 21 | |
| 21 | |
| 21 | |
| 20 | |
| 20 | |
| 20 | |
| 19 | |
| 19 | |
| 19 | |
| 19 | |
| 18 | |
| 18 | |
| 18 | |
| 18 | |
| 18 | |
| 18 | |
| 18 | |
| 18 | |
| 17 | |
| 17 | |
| 17 | |
| 17 | |
| 17 | |
| 17 | |
| 17 | |
| 17 | |
| 17 | |
| 17 | |
| 17 | |
| 17 | |
| 16 | |
| 16 | |
| 16 | |
| 16 | |
| 15 | |
| 15 | |
| 15 | |
| 15 | |
| 15 | |
| 15 | |
| 15 | |
| 15 | |
| 15 | |
| 15 | |
| 14 | |
| 14 | |
| 14 | |
| 14 | |
| 14 | |
| 13 | |
| 13 | |
| 13 | |
| 13 | |
| 13 | |
| 13 | |
| 13 | |
| 13 | |
| 13 | |
| 13 | |
| 13 | |
| 13 | |
| 12 | |
| 12 | |
| 12 | |
| 12 | |
| 12 | |
| 12 | |
| 12 | |
| 12 | |
| 12 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 11 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 10 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 9 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 8 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 7 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 6 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 5 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 4 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 3 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 2 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |
| 1 | |


