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Volumn 39, Issue 6, 2008, Pages 595-603

Vitamin E supplementation in rats with experimental diabetes mellitus: Analysis of myosin-V and nNOS immunoreactive myenteric neurons from terminal ileum

Author keywords

Diabetes mellitus; Myenteric neurons; Myosin V; Neuronal nitric oxide synthase; Vitamin E

Indexed keywords

ALPHA TOCOPHEROL; MYOSIN V;

EID: 56349170751     PISSN: 15672379     EISSN: None     Source Type: Journal    
DOI: 10.1007/s10735-008-9200-3     Document Type: Article
Times cited : (27)

References (47)
  • 2
    • 23644458308 scopus 로고    scopus 로고
    • Beneficial effects of vitamins C and e against oxidative stress in diabetic rats
    • 10.1016/j.nutres.2005.05.005
    • N Aksoy H Vural T Sabuncu O Arslan S Aksoy 2005 Beneficial effects of vitamins C and E against oxidative stress in diabetic rats Nutr Res 25 625 630 10.1016/j.nutres.2005.05.005
    • (2005) Nutr Res , vol.25 , pp. 625-630
    • Aksoy, N.1    Vural, H.2    Sabuncu, T.3    Arslan, O.4    Aksoy, S.5
  • 3
    • 0028861469 scopus 로고
    • Effect of age on NADPH-diaphorase-containing myenteric neurones of rat ileum and proximal colon
    • 10.1007/BF00318495
    • A Belai S Cooper G Burnstock 1995 Effect of age on NADPH-diaphorase- containing myenteric neurones of rat ileum and proximal colon Cell Tissue Res 279 379 383 10.1007/BF00318495
    • (1995) Cell Tissue Res , vol.279 , pp. 379-383
    • Belai, A.1    Cooper, S.2    Burnstock, G.3
  • 4
    • 0000002475 scopus 로고
    • D-glucose determination with glucose oxidase and peroxidase
    • Academic Press New York
    • Bergmeyer HU, Bernet E (1974) d-glucose determination with glucose oxidase and peroxidase. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp 1205-1215
    • (1974) Methods of Enzymatic Analysis , pp. 1205-1215
    • Bergmeyer, H.U.1    Bernet, E.2    Bergmeyer, H.U.3
  • 7
    • 0035856980 scopus 로고    scopus 로고
    • Biochemistry and molecular cell biology of diabetic complications
    • 10.1038/414813a
    • M Brownlee 2001 Biochemistry and molecular cell biology of diabetic complications Nature 414 813 820 10.1038/414813a
    • (2001) Nature , vol.414 , pp. 813-820
    • Brownlee, M.1
  • 9
    • 0032836681 scopus 로고    scopus 로고
    • Effects of antioxidants on nerve and vascular dysfunction in experimental diabetes
    • 10.1016/S0168-8227(99)00043-1
    • NE Cameron MA Cotter 1999 Effects of antioxidants on nerve and vascular dysfunction in experimental diabetes Diabetes Res Clin Pract 45 137 146 10.1016/S0168-8227(99)00043-1
    • (1999) Diabetes Res Clin Pract , vol.45 , pp. 137-146
    • Cameron, N.E.1    Cotter, M.A.2
  • 11
    • 0028791236 scopus 로고
    • Effects of natural free radical scavengers on peripheral nerve and neurovascular function in diabetic rats
    • 10.1007/BF00401760
    • MA Cotter A Love MJ Watt NE Cameron KC Dines 1995 Effects of natural free radical scavengers on peripheral nerve and neurovascular function in diabetic rats Diabetologia 38 1285 1294 10.1007/BF00401760
    • (1995) Diabetologia , vol.38 , pp. 1285-1294
    • Cotter, M.A.1    Love, A.2    Watt, M.J.3    Cameron, N.E.4    Dines, K.C.5
  • 12
    • 0033762532 scopus 로고    scopus 로고
    • Restricted diet rescues rat enteric motor neurones from age related cell death
    • 10.1136/gut.47.5.653
    • T Cowen RJ Johnson V Soubeyre RM Santer 2000 Restricted diet rescues rat enteric motor neurones from age related cell death Gut 47 653 660 10.1136/gut.47.5.653
    • (2000) Gut , vol.47 , pp. 653-660
    • Cowen, T.1    Johnson, R.J.2    Soubeyre, V.3    Santer, R.M.4
  • 13
    • 0028365723 scopus 로고
    • Quantitative study of the NADPH-diaphorase-positive myenteric neurons of the rat ileum
    • 10.1016/0306-4522(94)90236-4
    • C Cracco G Filogamo 1994 Quantitative study of the NADPH-diaphorase- positive myenteric neurons of the rat ileum Neuroscience 61 351 359 10.1016/0306-4522(94)90236-4
    • (1994) Neuroscience , vol.61 , pp. 351-359
    • Cracco, C.1    Filogamo, G.2
  • 15
    • 0027466546 scopus 로고
    • The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: The Rochester Diabetic Neuropathy Study
    • PJ Dyck KM Kratz JL Karnes WJ Litchy R Klein JM Pach DM Wilson PC O'Brien LJ Melton 3rd FJ Service 1993 The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study Neurology 43 817 824
    • (1993) Neurology , vol.43 , pp. 817-824
    • Dyck, P.J.1    Kratz, K.M.2    Karnes, J.L.3    Litchy, W.J.4    Klein, R.5    Pach, J.M.6    Wilson, D.M.7    O'Brien, P.C.8    Melton III, L.J.9    Service, F.J.10
  • 16
    • 0027068050 scopus 로고
    • Primary structure and cellular localization of chicken brain myosin-V (p190), an unconventional myosin with calmodulin light chains
    • 10.1083/jcb.119.6.1541
    • EM Espreafico RE Cheney M Matteoli AA Nascimento PV De Camilli RE Larson MS Mooseker 1992 Primary structure and cellular localization of chicken brain myosin-V (p190), an unconventional myosin with calmodulin light chains J Cell Biol 119 1541 1557 10.1083/jcb.119.6.1541
    • (1992) J Cell Biol , vol.119 , pp. 1541-1557
    • Espreafico, E.M.1    Cheney, R.E.2    Matteoli, M.3    Nascimento, A.A.4    De Camilli, P.V.5    Larson, R.E.6    Mooseker, M.S.7
  • 17
    • 17144417400 scopus 로고    scopus 로고
    • Morphoquantitative aspects of nitrergic myoenteric neurons from the stomach of diabetic rats supplemented with acetyl-l-carnitine
    • 10.1111/j.1439-0264.2004.00578.x
    • CE Fregonesi SL Molinari AM Alves MA Defani JN Zanoni RB Bazotte MH de Miranda Neto 2005 Morphoquantitative aspects of nitrergic myoenteric neurons from the stomach of diabetic rats supplemented with acetyl-l-carnitine Anat Histol Embryol 34 93 97 10.1111/j.1439-0264.2004.00578.x
    • (2005) Anat Histol Embryol , vol.34 , pp. 93-97
    • Fregonesi, C.E.1    Molinari, S.L.2    Alves, A.M.3    Defani, M.A.4    Zanoni, J.N.5    Bazotte, R.B.6    De Miranda Neto, M.H.7
  • 18
    • 0036025229 scopus 로고    scopus 로고
    • Morphoquantitative effects of acute diabetes on the myenteric neurons of the proximal colon of adult rats
    • 10.1590/S0004-282X2002000400012
    • MM Furlan SL Molinari MH Miranda Neto 2002 Morphoquantitative effects of acute diabetes on the myenteric neurons of the proximal colon of adult rats Arq Neuropsiquiatr 60 576 581 10.1590/S0004-282X2002000400012
    • (2002) Arq Neuropsiquiatr , vol.60 , pp. 576-581
    • Furlan, M.M.1    Molinari, S.L.2    Miranda Neto, M.H.3
  • 20
    • 0033674676 scopus 로고    scopus 로고
    • Streptozotocin-induced diabetic duration is important to determine changes in the number and basophily of myenteric neurons
    • 10.1590/S0004-282X2000000600010
    • L Hernandes RB Bazotte P Gama MH Miranda-Neto 2000 Streptozotocin-induced diabetic duration is important to determine changes in the number and basophily of myenteric neurons Arq Neuropsiquiatr 58 1035 1039 10.1590/S0004- 282X2000000600010
    • (2000) Arq Neuropsiquiatr , vol.58 , pp. 1035-1039
    • Hernandes, L.1    Bazotte, R.B.2    Gama, P.3    Miranda-Neto, M.H.4
  • 22
    • 15944383353 scopus 로고    scopus 로고
    • Choline acetyltransferase and inducible nitric oxide synthase are increased in myenteric plexus of diabetic guinea pig
    • 10.1016/j.autneu.2004.12.002
    • KJ Lepard 2005 Choline acetyltransferase and inducible nitric oxide synthase are increased in myenteric plexus of diabetic guinea pig Auton Neurosci 118 12 24 10.1016/j.autneu.2004.12.002
    • (2005) Auton Neurosci , vol.118 , pp. 12-24
    • Lepard, K.J.1
  • 23
    • 0021346760 scopus 로고
    • Myenteric plexus in streptozotocin-treated rats: Neurochemical and histochemical evidence for diabetic neuropathy in the gut
    • J Lincoln JT Bokor R Crowe SG Griffith AJ Haven G Burnstock 1984 Myenteric plexus in streptozotocin-treated rats: neurochemical and histochemical evidence for diabetic neuropathy in the gut Gastroenterology 86 654 661
    • (1984) Gastroenterology , vol.86 , pp. 654-661
    • Lincoln, J.1    Bokor, J.T.2    Crowe, R.3    Griffith, S.G.4    Haven, A.J.5    Burnstock, G.6
  • 24
    • 0016335085 scopus 로고
    • Periodate-lysine-paraformaldehyde fixative: A new version for immunoelectron microscopy
    • IW McLean PK Nakane 1974 Periodate-lysine-paraformaldehyde fixative: a new version for immunoelectron microscopy J Histochem Cytochem 22 1077 1083
    • (1974) J Histochem Cytochem , vol.22 , pp. 1077-1083
    • McLean, I.W.1    Nakane, P.K.2
  • 25
    • 0035289371 scopus 로고    scopus 로고
    • Regional differences in the number and type of myenteric neurons of the ileum of rats: A comparison of techniques of the neuronal evidentiation
    • MH Miranda Neto SL Molinari MR Natali DM Sant'Ana 2001 Regional differences in the number and type of myenteric neurons of the ileum of rats: a comparison of techniques of the neuronal evidentiation Arq Neuropsiquiatr 59 54 59
    • (2001) Arq Neuropsiquiatr , vol.59 , pp. 54-59
    • Miranda Neto, M.H.1    Molinari, S.L.2    Natali, M.R.3    Sant'Ana, D.M.4
  • 26
    • 24044513942 scopus 로고    scopus 로고
    • A review on the role of antioxidants in the management of diabetes and its complications
    • 10.1016/j.biopha.2005.07.002
    • R Rahimi S Nikfar B Larijani M Abdollahi 2005 A review on the role of antioxidants in the management of diabetes and its complications Biomed Pharmacother 59 365 373 10.1016/j.biopha.2005.07.002
    • (2005) Biomed Pharmacother , vol.59 , pp. 365-373
    • Rahimi, R.1    Nikfar, S.2    Larijani, B.3    Abdollahi, M.4
  • 27
    • 0030011675 scopus 로고    scopus 로고
    • Antioxidants in peripheral nerve
    • 10.1016/0891-5849(95)02183-3
    • FJ Romero 1996 Antioxidants in peripheral nerve Free Radic Biol Med 20 925 932 10.1016/0891-5849(95)02183-3
    • (1996) Free Radic Biol Med , vol.20 , pp. 925-932
    • Romero, F.J.1
  • 28
    • 0028103912 scopus 로고
    • Survival of the population of the NADPH-diaphorase stained myenteric neurons in the small intestine of aged rats
    • 10.1016/0165-1838(94)90131-7
    • RM Santer 1994 Survival of the population of the NADPH-diaphorase stained myenteric neurons in the small intestine of aged rats J Auton Nerv Syst 49 115 121 10.1016/0165-1838(94)90131-7
    • (1994) J Auton Nerv Syst , vol.49 , pp. 115-121
    • Santer, R.M.1
  • 29
    • 0036356058 scopus 로고    scopus 로고
    • Neuropathology and pathogenesis of diabetic autonomic neuropathy
    • 10.1016/S0074-7742(02)50080-5
    • RE Schmidt 2002 Neuropathology and pathogenesis of diabetic autonomic neuropathy Int Rev Neurobiol 50 257 292 10.1016/S0074-7742(02)50080-5
    • (2002) Int Rev Neurobiol , vol.50 , pp. 257-292
    • Schmidt, R.E.1
  • 30
    • 0035085986 scopus 로고    scopus 로고
    • Effect of α-tocopherol supplementation on the ultrastructural abnormalities of peripheral nerves in experimental diabetes
    • 10.1046/j.1529-8027.2001.006001033.x
    • AK Sharma AS Ponery PA Lawrence I Ahmed SMA Bastaki S Dhanasekaran RS Sheen E Adeghate 2001 Effect of α-tocopherol supplementation on the ultrastructural abnormalities of peripheral nerves in experimental diabetes J Peripher Nerv Syst 6 33 39 10.1046/j.1529-8027.2001.006001033.x
    • (2001) J Peripher Nerv Syst , vol.6 , pp. 33-39
    • Sharma, A.K.1    Ponery, A.S.2    Lawrence, P.A.3    Ahmed, I.4    Bastaki, S.M.A.5    Dhanasekaran, S.6    Sheen, R.S.7    Adeghate, E.8
  • 31
    • 31344442543 scopus 로고    scopus 로고
    • Diabetes only affects nitric oxide synthase-containing myenteric neurons that do not contain heme oxygenase 2
    • 10.1016/j.brainres.2005.11.057
    • HR Shotton J Lincoln 2006 Diabetes only affects nitric oxide synthase-containing myenteric neurons that do not contain heme oxygenase 2 Brain Res 1068 248 256 10.1016/j.brainres.2005.11.057
    • (2006) Brain Res , vol.1068 , pp. 248-256
    • Shotton, H.R.1    Lincoln, J.2
  • 32
    • 0037220826 scopus 로고    scopus 로고
    • The effectiveness of treatments of diabetic autonomic neuropathy is not the same in autonomic nerves supplying different organs
    • 10.2337/diabetes.52.1.157
    • HR Shotton S Clarke J Lincoln 2003 The effectiveness of treatments of diabetic autonomic neuropathy is not the same in autonomic nerves supplying different organs Diabetes 52 157 164 10.2337/diabetes.52.1.157
    • (2003) Diabetes , vol.52 , pp. 157-164
    • Shotton, H.R.1    Clarke, S.2    Lincoln, J.3
  • 33
    • 1942485285 scopus 로고    scopus 로고
    • Prevention and partial reversal of diabetes-induced changes in enteric nerves of the rat ileum by combined treatment with α-lipoic and evening primrose oil
    • 10.1016/j.autneu.2004.02.004
    • HR Shotton S Broadbent J Lincoln 2004 Prevention and partial reversal of diabetes-induced changes in enteric nerves of the rat ileum by combined treatment with α-lipoic and evening primrose oil Auton Neurosci 111 57 65 10.1016/j.autneu.2004.02.004
    • (2004) Auton Neurosci , vol.111 , pp. 57-65
    • Shotton, H.R.1    Broadbent, S.2    Lincoln, J.3
  • 34
    • 33847040675 scopus 로고    scopus 로고
    • Effect of aminoguanidine treatment on diabetes-induced changes in myenteric plexus of rat ileum
    • 10.1016/j.autneu.2006.08.007
    • HR Shotton A Adams J Lincoln 2007 Effect of aminoguanidine treatment on diabetes-induced changes in myenteric plexus of rat ileum Auton Neurosci 132 16 26 10.1016/j.autneu.2006.08.007
    • (2007) Auton Neurosci , vol.132 , pp. 16-26
    • Shotton, H.R.1    Adams, A.2    Lincoln, J.3
  • 35
    • 34547691067 scopus 로고    scopus 로고
    • Role of vascular reactive oxygen species in development of vascular abnormalities in diabetes
    • Suppl 1. 10.1016/j.diabres.2007.01.036
    • SM Son 2007 Role of vascular reactive oxygen species in development of vascular abnormalities in diabetes Diabetes Res Clin Pract 77 Suppl 1 S65 S70 10.1016/j.diabres.2007.01.036
    • (2007) Diabetes Res Clin Pract , vol.77
    • Son, S.M.1
  • 36
    • 0014202889 scopus 로고
    • Fixation of ejaculated spermatozoa for electron microscopy
    • 10.1038/216173a0
    • M Stefanini C De Martino L Zamboni 1967 Fixation of ejaculated spermatozoa for electron microscopy Nature 216 173 174 10.1038/216173a0
    • (1967) Nature , vol.216 , pp. 173-174
    • Stefanini, M.1    De Martino, C.2    Zamboni, L.3
  • 37
    • 34247337740 scopus 로고    scopus 로고
    • Diabetic rats supplemented with l-glutamine: A study of immunoreactive myosin-V myenteric neurons and the proximal colonic mucosa
    • 10.1007/s10620-006-9564-8
    • CM Tashima EA Tronchini RV Pereira RB Bazotte JN Zanoni 2007 Diabetic rats supplemented with l-glutamine: a study of immunoreactive myosin-V myenteric neurons and the proximal colonic mucosa Dig Dis Sci 52 1233 1241 10.1007/s10620-006-9564-8
    • (2007) Dig Dis Sci , vol.52 , pp. 1233-1241
    • Tashima, C.M.1    Tronchini, E.A.2    Pereira, R.V.3    Bazotte, R.B.4    Zanoni, J.N.5
  • 38
    • 33749986298 scopus 로고    scopus 로고
    • Free radicals and antioxidants in normal physiological functions and human disease
    • 10.1016/j.biocel.2006.07.001
    • M Valko D Leibfritz J Moncol MTD Cronin M Mazur J Telser 2007 Free radicals and antioxidants in normal physiological functions and human disease Int J Biochem Cell Biol 39 44 84 10.1016/j.biocel.2006.07.001
    • (2007) Int J Biochem Cell Biol , vol.39 , pp. 44-84
    • Valko, M.1    Leibfritz, D.2    Moncol, J.3    Cronin, M.T.D.4    Mazur, M.5    Telser, J.6
  • 39
    • 0024815737 scopus 로고
    • In vitro and in vivo reduction of erythrocyte sorbitol by ascorbic acid
    • 10.2337/diabetes.38.8.1036
    • JA Vinson ME Staretz P Bose HM Kassm BS Basalyga 1989 In vitro and in vivo reduction of erythrocyte sorbitol by ascorbic acid Diabetes 38 1036 1041 10.2337/diabetes.38.8.1036
    • (1989) Diabetes , vol.38 , pp. 1036-1041
    • Vinson, J.A.1    Staretz, M.E.2    Bose, P.3    Kassm, H.M.4    Basalyga, B.S.5
  • 40
    • 0030730656 scopus 로고    scopus 로고
    • Nitric oxide synthase (NOS) expression in the myenteric plexus of streptozotocin-diabetic rats
    • 10.1023/A:1018830820537
    • HF Wrzos A Cruz R Polavarapu D Shearer A Ouyang 1997 Nitric oxide synthase (NOS) expression in the myenteric plexus of streptozotocin-diabetic rats Dig Dis Sci 42 2106 2110 10.1023/A:1018830820537
    • (1997) Dig Dis Sci , vol.42 , pp. 2106-2110
    • Wrzos, H.F.1    Cruz, A.2    Polavarapu, R.3    Shearer, D.4    Ouyang, A.5
  • 41
    • 0035903993 scopus 로고    scopus 로고
    • Enhanced colonic peristalsis by impairment of nitrergic enteric neurons in spontaneously diabetic rats
    • 10.1016/S1566-0702(01)00317-4
    • S Yoneda M Kadowaki H Kuramoto H Fukui M Takaki 2001 Enhanced colonic peristalsis by impairment of nitrergic enteric neurons in spontaneously diabetic rats Auton Neurosci 92 65 71 10.1016/S1566-0702(01)00317-4
    • (2001) Auton Neurosci , vol.92 , pp. 65-71
    • Yoneda, S.1    Kadowaki, M.2    Kuramoto, H.3    Fukui, H.4    Takaki, M.5
  • 42
    • 27744549410 scopus 로고    scopus 로고
    • Effect of combined vitamin e and insulin administration on renal damage in diabetic rats fed a high cholesterol diet
    • 10.1248/bpb.28.2080
    • M Yoshida H Kimura K Kyuki M Ito 2005 Effect of combined vitamin E and insulin administration on renal damage in diabetic rats fed a high cholesterol diet Biol Pharm Bull 28 2080 2086 10.1248/bpb.28.2080
    • (2005) Biol Pharm Bull , vol.28 , pp. 2080-2086
    • Yoshida, M.1    Kimura, H.2    Kyuki, K.3    Ito, M.4
  • 43
    • 0036514418 scopus 로고    scopus 로고
    • Terminal ileum submucous plexus: Study of VIP-ergic neurons of diabetic rats treated with ascorbic acid
    • 10.1590/S0004-282X2002000100007
    • JN Zanoni L Hernandes RB Bazotte MH Miranda Neto 2002 Terminal ileum submucous plexus: study of VIP-ergic neurons of diabetic rats treated with ascorbic acid Arq Neuropsiquiatr 60 32 37 10.1590/S0004-282X2002000100007
    • (2002) Arq Neuropsiquiatr , vol.60 , pp. 32-37
    • Zanoni, J.N.1    Hernandes, L.2    Bazotte, R.B.3    Miranda Neto, M.H.4
  • 44
    • 0037469917 scopus 로고    scopus 로고
    • Evaluation of the population of NADPH-diaphorase-stained and myosin-V myenteric neurons in the ileum of chronically streptozotocin-diabetic rats treated with ascorbic acid
    • 10.1016/S1566-0702(02)00266-7
    • JN Zanoni NC Buttow RB Bazotte MH Miranda Neto 2003 Evaluation of the population of NADPH-diaphorase-stained and myosin-V myenteric neurons in the ileum of chronically streptozotocin-diabetic rats treated with ascorbic acid Auton Neurosci 104 32 38 10.1016/S1566-0702(02)00266-7
    • (2003) Auton Neurosci , vol.104 , pp. 32-38
    • Zanoni, J.N.1    Buttow, N.C.2    Bazotte, R.B.3    Miranda Neto, M.H.4
  • 45
    • 20444471397 scopus 로고    scopus 로고
    • Effects of supplementation with ascorbic acid for a period of 120 days on the myosin-V and NADPHd positive myenteric neurons of the ileum of rats
    • 10.1111/j.1439-0264.2005.00584.x
    • JN Zanoni P De Freitas RVF Pereira MA Dos Santos Pereira MH De Miranda Neto 2005 Effects of supplementation with ascorbic acid for a period of 120 days on the myosin-V and NADPHd positive myenteric neurons of the ileum of rats Anat Histol Embryol 34 149 153 10.1111/j.1439-0264.2005.00584.x
    • (2005) Anat Histol Embryol , vol.34 , pp. 149-153
    • Zanoni, J.N.1    De Freitas, P.2    Pereira, R.V.F.3    Dos Santos Pereira, M.A.4    De Miranda Neto, M.H.5
  • 46
    • 33947245421 scopus 로고    scopus 로고
    • Effect of the ascorbic acid treatment on the NADHd positive myenteric neurons of diabetic rats proximal colon
    • 10.1590/S1516-89132007000100004
    • JN Zanoni RVF Pereira P Freitas 2007 Effect of the ascorbic acid treatment on the NADHd positive myenteric neurons of diabetic rats proximal colon Braz Arch Biol Technol 50 31 38 10.1590/S1516-89132007000100004
    • (2007) Braz Arch Biol Technol , vol.50 , pp. 31-38
    • Zanoni, J.N.1    Pereira, R.V.F.2    Freitas, P.3
  • 47
    • 34547681377 scopus 로고    scopus 로고
    • Diabetes mellitus and the peripheral nervous system: Manifestations and mechanisms
    • 10.1002/mus.20785
    • DW Zochodne 2007 Diabetes mellitus and the peripheral nervous system: manifestations and mechanisms Muscle Nerve 36 144 166 10.1002/mus.20785
    • (2007) Muscle Nerve , vol.36 , pp. 144-166
    • Zochodne, D.W.1


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