The neuroprotective effects of PACAP in rat models of Parkinson's disease and neonatal neuronal damage  Page description

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Details of project

  
Identifier
46589
Type K
Principal investigator Reglődi, Dóra
Title in Hungarian PACAP neuroprotektív hatása Parkinson-kór és újszülöttkori neuronális károsodás patkány modellekben
Title in English The neuroprotective effects of PACAP in rat models of Parkinson's disease and neonatal neuronal damage
Panel Neurosciences
Department or equivalent Institute of Anatomy (University of Pécs)
Participants Lengvári, István
Pethoné dr. Lubics, Andrea
Tamás, Andrea
Starting date 2004-01-01
Closing date 2008-06-30
Funding (in million HUF) 6.708
FTE (full time equivalent) 0.00
state closed project





 

Final report

  
Results in Hungarian
A pályázat szerves folytatása volt a korábbi T034491 projektnek. A jelen pályázatban PACAP neuroprotektív hatásainak vizsgálatát folytattuk, az eredeti terv szerint két fő téma köré csoportosítva: a PACAP hatása bazális ganglionok károsodásában és újszülöttkori agykárosodásban. Kimutattuk, hogy a PACAP csökkenti a dopaminerg sejtpusztulást a substantia nigrában és jelentősen javítja a neurológiai tüneteket patkány Parkinson kór modellben. Leírtuk az unilaterális substantia nigra roncsolás modell és ebben a PACAP protektív hatásainak kor és nemfüggését. Igazoltuk a PACAP védő hatását Huntington chorea, neurotrauma modellekben, valamint toxicus és ischemiás retinadegenerációban. Igazoltuk, hogy a PACAP nemcsak neuroprotektív, hanem általános citoprotektív tulajdonságú: védő hatást fejt ki szívizom-és endothelsejtekben, vese és bélischemiában. A hatásmechanizmust tekintve igazoltuk, hogy ezen rendszerekben a PACAP antiapoptotikus tulajdonságú, in vitro és in vivo gátolja a proapoptotikus és aktiválja az antiapoptotikus jelátviteli útvonalakat. Eddig nem ismert jelátviteli útvonalak igazolásán kívül leírtuk, hogy a PACAP hatása jelentős különbségeket mutat a kor, nem, napi ritmus és sejttípustól függően. Újszülöttkori léziókban (toxicus, hypoxiás) leírtuk a kora postnatalis neuronális fejlődést, és kimutattuk a PACAP védő hatását bizonyos reflexfejlődési mintázatra. A támogatás segítségével született közlemények összesített impakt faktora 139,807 (absztraktok nélkül).
Results in English
We continued the investigation on the neuroprotective effects of PACAP. The focus of our research was to examine the neuroprotective effects in models of basal ganglia diseases and neonatal brain injuries. We showed that PACAP treatment ameliorates the substantia nigra dopaminergic cell loss and improves the neurological deficits in a model of Parkinson`s disease. We examined how this unilateral substantia nigra degeneration model and the effects of PACAP depend on age and gender. We have provided evidence that PACAP is also protective in models of Huntington chorea, brain trauma, toxic and ischemic retinal degeneration. We have also shown that PACAP is not only neuroprotective, but is a general cytoprotective peptide: it has protective effects in cardiomyocytes, endothelial cells, kidney and intestinal ischemia. Considering the neuroprotective mechanism, we showed that PACAP has antiapoptotic effects in these models, it activates the antiapoptotic and inhibits the proapoptotic signaling pathways both in vitro and in vivo. In addition to providing evidence for new neuroprotective signaling mechanisms, we also showed that the protective effects of PACAP depend on age, gender, diurnal cycle and cell type.We described the early postnatal neurobehavioral development in toxic and hypoxic injuries and the protective effects of PACAP on some neurological reflexes. The impact factor of the publications with the help of this grant is 139.807 (without abstracts).
Full text https://www.otka-palyazat.hu/download.php?type=zarobeszamolo&projektid=46589
Decision
Yes





 

List of publications

  
Józsa R; Hollósy T; Tamás A; Tóth G; Lengvári I; Reglődi D: Pituitary adenylate cyclase activating polypeptide plays a role in olfactory memory formation in chicken., Peptides 26: 2344-2350, 2005
Faluhelyi N; Reglődi D; Csernus V: Development of the circadian melatonin rhythm and its responsiveness to PACAP in the embryonic chicken pineal gland, Ann NY Acad Sci 1040: 305-309, 2005
Farkas O; Tamás A; Zsombok A; Reglődi D; Pál J; Büki A; Lengvári I; Povlishok JT; Dóczi T: Effects of pituitary adenylate cyclase activating polypeptide (PACAP) in a rat model of traumatic brain injury, Regul Pept 123: 69-75, 2004
Hollósy T; Józsa R; Jakab B; Németh J; Lengvári I; Reglődi D: Effects of in ovo treatment with PACAP antagonist on general activity, motor and social behavior in chickens, Regul Pept 123: 99-106, 2004
Faluhelyi N; Reglődi D; Lengvári I; Csernus V: Development of the circadian melatonin rhythm and the effect of PACAP on melatonin production in the embryonic chicken pineal gland. An in vitro study, Regul Pept 123: 23-28, 2004
Reglődi D; Tamás A; Lubics A; Szalontay L; Lengvári I: Morphological and functional effects of PACAP in a 6-hydroxydopamine-induced lesion of the substantia nigra in rats, Regul Pept 123: 85-94, 2004
Lubics A; Reglődi D; Tamás A; Kiss P; Szalai M; Szalontay L; Lengvári I: Neurological reflexes and early motor behavior in rats subjected to neonatal hypoxic/ischemic injury, Behav Brain Res 157: 157-165, 2005
Tamás A; Gábriel R; Rácz B; Dénes V; Kiss P; Lubics A; Lengvári I; Reglődi D: Effects of pituitary adenylate cyclase activating polypeptide in retinal degeneration induced by monosodium-glutamate, Neurosci Lett 372: 110-113, 2004
Kiss P; Tamás A; Lubics A; Szalai M; Szalontay L; Lengvári I; Reglődi D: Development of neurological reflexes and motor coordination in rats neonatally treated with monosodium glutamate, Neurotoxic Res 8: 235-244, 2005
Reglődi D; Tamás A; Somogyvári-Vigh A: Pituitary adenylate cyclase activating polypeptide in animal models of neurodegenerative disorders - implications for Huntington and Parkinson`s diseases, Lett Drug Dis Discov 2: 239-244, 2005
Gasz B; Rácz B; Rőth E; Borsiczky B; Ferencz A; Tamás A; Cserepes B; Lubics A; Gallyas F Jr; Tóth G; Lengvári I; Reglődi D: Pituitary adenylate cyclase activating polypeptide protects cardiomyocytes against oxidative stress-induced apoptosis, Peptides 27: 87-94, 2006
Babai N; Atlasz T; Tamás A; Reglődi D; Kiss P; Gábriel R: Degree of damage compensation by various PACAP treatments in monosodium glutamate-induced retina degeneration, Neurotoxic Res 8: 227-233, 2005
Tamás A; Zsombok A; Farkas O; Reglődi D; Pál J; Büki A; Lengvári I; Povlishock JT; Dóczi T: Postinjury administration of pituitary adenylate cyclase activating polypeptide (PACAP) attenuates traumatically induced axonal injury in rats, J Neurotrauma 23: 686-695, 2006
Reglődi D; Tamás A; Lengvári I; Tóth G; Szalontay L; Lubics A: Comparative study on the effects of PACAP in young, aging, and castrated males in a rat model of Parkinson`s disease, Ann NY Acad Sci 1070: 518-524, 2006
Babai N; Atlasz T; Tamás A; Reglődi D; Tóth G; Kiss P; Gábriel R: Search for the optimal monosodium glutamate treatment schedule to study the neuroprotective effects of PACAP in the retina, Ann NY Acad Sci 1070: 149-155, 2006
Rácz B; Tamás A; Kiss P; Tóth G; Gasz B; Borsiczky B; Ferencz A; Gallyas F Jr; Rőth E; Reglődi D: Involvement of ERK and CREB signalling pathways in the protective effect of PACAP on monosodium glutamate-induced retinal lesion, Ann NY Acad Sci 1070: 507-511, 2006
Kiss P; Tamás A; Lubics A; Lengvári I; Szalai M; Hauser D; Horváth Zs; Rácz B; Gábriel R; Babai N; Tóth G; Reglődi D: Effects of systemic PACAP treatment in monosodium glutamate-induced behavioral changes and retinal degeneration, Ann NY Acad Sci 1070: 365-370, 2006
Tamás A; Lubics A; Lengvári I; Reglődi D: Protective effects of PACAP in excitotoxic striatal lesion, Ann NY Acad Sci 1070: 570-574, 2006
Molnár L; Pollák E; Boros Á; Reglődi D; Tamás A; Lengvári I; Arimura A; Lubics A: Comparative anatomy of PACAP-immunoreactive structures in the ventral nerve cord ganglia of lumbricid Oligochaetes, Ann NY Acad Sci 1070: 427-430, 2006
Németh J; Tamás A; Józsa R; Horváth JE; Jakab B; Lengvári I; Arimura A; Lubics A; Reglődi D: Changes in PACAP levels in the central nervous system after ovariectomy and castration, Ann NY Acad Sci 1070: 468-473, 2006
Atlasz T; Köszegi Zs; Babai N; Tamás A; Reglődi D; Kovács P; Hernádi I; Gábriel R: Microiontophoretically applied PACAP blocks excitatory effects of kainic acid in vivo, Ann NY Acad Sci 1070: 143-148, 2006
Faluhelyi N; Reglődi D; Csernus V: The effects of PACAP and VIP on the in vitro melatonin secretion from the embryonic chicken pineal gland, Ann NY Acad Sci 1070: 271-275, 2006
Józsa R; Németh J; Tamás A; Hollósy T; Lubics A; Jakab B; Oláh A; Lengvári I; Arimura A; Reglődi D: Short-term fasting differentially alters PACAP and VIP levels in the brains of rats and chickens, Ann NY Acad Sci 1070: 354-358, 2006
Gasz B; Rácz B; Rőth E; Borsiczky B; Tamás A; Boronkai Á; Tóth G; Reglődi D: PACAP inhibits oxidative stress-induced activation of MAP kinase dependent apoptotic pathway in cultured cardiomyocytes, Ann NY Acad Sci i1070: 293-297, 2006
Józsa R; Hollósy T; Németh J; Tamás A; Lubics A; Jakab B; Oláh A; Arimura A; Reglődi D: Presence of PACAP and VIP in embryonic chicken brain, Ann NY Acad Sci1070: 348-353, 2006
Tamás A; Lubics A; Lengvári I; Reglődi D: Effects of age, gender, and gonadectomy on neurochemistry and behavior in animal models of Parkinson`s disease, Endocrine 29: 275-287, 2006
Lubics A; Tamás A; Szalai M; Ábrahám H; Lengvári I; Reglődi D: Effects of PACAP treatment in a kainic acid induced hippocampal injury, Regul Pept 130: 169, 2005
Nagy Cs; Maász R; Tamás A; Nagy F; Lengvári I; Reglődi D; Lubics A: Time course of sciatic nerve regeneration in rats: a complex behavioral and electromyographical study, Clin Neurosci/Ideggy. Szmle 58: 69., 2005
Németh J; Reglődi D; Pozsgai G; Szabó Á; Elekes K; Pintér E; Szolcsányi J; Helyes Zs: Effect of PACAP-38 on sensory neuropeptide release and neurogenic inflammation in rats and mice, Neuroscience 143: 223-230, 2006
Racz B; Reglodi D; Kiss P; Babai N; Atlasz T; Gabriel R; Lubics A; Gallyas F Jr; Gasz B; Toth G; Roth E; Hegyi O; Lengvari I; Tamas A: In vivo neuroprotection by PACAP in excitotoxic retinal injury: review of effects on retinal morphology and apoptotic signal transduction., Int J Neuroprot Neurodeg 2: 80-85, 2006
Németh J; Jakab B; Józsa R; Hollósy T; Tamás A; Lubics A; Lengvári I; Kiss P; Oberritter Zs; Horváth B; Szilvássy Z; Reglődi D: PACAP-27 radioimmunoassay: Description and application of a novel method., J Radioanal Nucl Chem 273: 327-332, 2007
Kiss P; Reglődi D; Tamás A; Lubics A; Lengvári I; Józsa R; Somogyvári-Vigh A; Szilvássy Z; Németh J: Changes of PACAP levels in the brain show gender differences following short-term water and food deprivation, Gen Comp Endocrinol 152: 225-230, 2007
Babai N; Atlasz T; Schaffer D; Reglődi D; Tamás A; Kiss P; Szalai M; Gábriel R: Comparison of three different neurodegeneration models in the rat retina: monosdium glutamate (MSG), hypoxic insult combined with unilateral carotis occlusion and bilater, Clin Neurosci/Ideggy. Szmle. 59(S1): 8., 2006
Gaszner B; Korosi A; Derks N; Farkas J; Reglődi D; Csernus V; Kozicz T: Effects of maternal deprivation on the Edinger-Westphal urocortin 1 system, Clin Neurosci/Ideggy. Szmle. 59(S1): 22., 2006
Varhalmi E, Somogyi I, Kiszler G, Nemeth J, Reglodi D, Lubics A, Kiss P, Tamas A, Pollak E, Molnar L.: Expression of PACAP-like compounds during the caudal regeneration of the earthworm Eisenia fetida, J Mol Neurosci in press, 2008
Racz B, Horvath G, Faluhelyi N, Nagy AD, Tamas A, Kiss P, Gallyas F, Toth G, Gaszner B, Csernus V, Reglodi D.: Effects of PACAP on the circadian changes of signaling pathways in chicken pinealocytes, J Mol Neurosci in press, 2008
Boros A, Reglodi D, Herbert Z, Kiszler G, Nemeth J, Lubics A, Kiss P, Tamas A, Shioda S, Matsuda K, Pollak E, Molnar L.: Changes in the expression of PACAP-like compounds during the embryonic development of the earthworm Eisenia fetida., J Mol Neurosci in press, 2008
Reglodi D, Borzsei R, Bagoly T, Boronkai A, Racz B, Tamas A, Kiss P, Horvath G, Brubel R, Nemeth J, Toth G, Helyes Z.: Agonistic behavior of PACAP6-38 on sensory nerve terminals and cytotrophoblast cells, J Mol Neurosci in press, 2008
Pirger Zs, Nemeth J, Hiripi L, Toth G, Kiss P, Lubics A, Tamas A, Hernadi L, Kiss T, Reglodi D: PACAP has anti-apoptotic effect in the salivary gland of an inverebrate species, Helix pomatia, J Mol Neurosci in press, 2008
Ferencz A, Racz B, Tamas A, Reglodi D, Lubics A, Nemeth J, Nedvig K, Kalmar-Nagy K, Horvath OP, Weber G, Roth E: Influence of PACAP on oxidative stress and tissue injury following small bowel autotransplantation, J Mol Neurosci in press, 2008
Gaál V, Márk L, Kiss P, Kustos I, Tamás A, Kocsis B, Lubics A, Németh V, Németh A, Lujber L, Pytel J, Tóth G, Reglődi D: Investigation of the effects of PACAP on the composition of tear and endolymph proteins., J Mol Neurosci in press, 2008
Szakály P, Kiss P, Lubics A, Magyarlaki T, Tamás A, Rácz B, Lengvári I, Tóth G, Reglődi D.: Effects of PACAP on survival and renal morphology in rats subjected to renal ischemia-reperfusion, J Mol Neurosci in press, 2008
Atlasz T, Szabadfi K, Kiss P, Babai N, Kőszegi Z, Tamás A, Reglődi D, Gábriel R.: PACAP-mediated neuroprotection of neurochemically identified cell types in MSG-induced retinal regeneration, J Mol Neurosci in press, 2008
Hernadi L, Pirger Zs, Kiss T, Nemeth J, Mark L, Kiss P, Tamas A, Lubics A, Toth G, Shioda S, Reglodi D: The presence and distribution of pituitary adenylate cyclase activating polypeptide (PACAP) and its receptor (PAC1-R) in the snail Helix pomatia., Neuroscience, 2008
Kövesdi E, Tamás A, Reglődi D, Farkas O, Pál J, Tóth G, Bukovics P, Dóczi T, Büki A.: Posttraumatic administration of pituitary adenylate cyclase activating polypeptide in central fluid percussion injury in rats, Neurotox Res 13: 71-78, 2008
Molnár L, Pollák E, Boros A, Shioda S, Nakajo S, Tamás A, Lengvári I, Reglődi D, Lubics A.: PAC1 receptor localization in a model nervous system: light and electron microscopic immunocytochemistry on the earthworm ventral nerve cord ganglia., Regul Pept 145: 96-104, 2008
Atlasz T, Babai N, Reglődi D, Kiss P, Tamás A, Bari F, Domoki F, Gábriel R.: Diazoxide is protective in the rat retina against ischemic injury induced by bilateral carotid occlusion and glutamate-induced degeneration, Neurotox Res 12: 105-111, 2007
Kövesdi E, Czeitel E, Tamás A, Reglődi D, Szellár D, Pál J, Bukovics P, Dóczi T, Büki A: Rescuing neurons and glia: is inhibition of apoptosis useful?, Progr Brain Res 161: 81-95, 2007
Rácz B, Reglődi D, Fodor B, Gasz B, Lubics A, Gallyas F Jr, Rőth E, Borsiczky B.: Hyperosmotic stress-induced apoptotic signaling pathways in chondrocytes., Bone 40: 1536-1543, 2007
Kiss P, Reglodi D, Farkas J, Szalai M, Tamas A, Lubics A, Lengvari I, Gaszner B, Szogyi D, Hauser D, Koppan M.: Comparison of the neurobehavioral development following toxic, hypoxic injuries and maternal deprivation in neonatal rats., Neurotox Res 13: 136, 2008
Racz B, Gasz B, Gallyas F, Kiss P, Tamas A, Jozsa R, Lubics A, Lengvari , Toth G, Roth E, Reglodi D: Common antiapoptotic mechanisms in the neuro-and cardioprotective effects of PACAP, Neurotox Res 13: 134, 2008
Jozsa R, Reglodi D, Cornelissen G, Nemeth J, Hollosy T, Bakken EE, Halberg F: Rhythm of PACAP leves in embryonic chicken brain, heart and intestinal system, J Mol Neurosci 33: 340, 2007
Sandor K, Bolcskei K, Elekes K, Pinter E, Petho G, Reglodi D, Szolcsanyi J, Helyes Zs: Peripheral anti-nociceptive effect of PACAP38 in rats and mice, J Mol Neurosci 33: 340, 2007
Kiss P, Hauser D, Tamas A, Horvath Zs, Lengvari I, Reglodi D.: Effects of perinatal PACAP and PACAP antagonist treatment on novelty-seeking behavior in adolescent rats, J Mol Neurosci 33: 340, 2007
Somogyi I, Varhalmi E, Pollak E, Reglodi D, Shioda S, Lubics A, Molnar L: PACAP and PAC1 receptor immunoreactivity in some coelomocytes of the regenerating Eisenia fetida, J Mol Neurosci 33: 332, 2007
Nemeth A, Racz B, Kiss P, Kustos I, Lujber L, Nagy Gy, Pytel J, Hollosy T, Lubics A, Brubel R, Lengvari I, Reglodi D, Tamas A: Effect of PACAP on oxidative stress-induced apoptopsis of cochlear cells and on endolymph protein, J Mol Neurosci 33: 331, 2007
Racz B, Horvath G, Faluhelyi N, Nagy AD, Gallyas F Jr, Tamas A, Kiss P, Csernus V, Reglodi D.: Different effects of pitutiary adenylate cyclase activating polypeptide (PACAP) against oxidative stress induced cell death during light and dark phases of chicken pineal cell culture, J Mol Neurosci 33:330, 2007
Reglődi D, Fábián Zs, Tamás A, Lubics A, Szeberényi J , Alexy T, Tóth K, Márton Zs, Borsiczky B, Rőth E, Szalontay L, Lengvári I: Effects of PACAP on in vitro and in vivo neuronal cell death, platelet aggregation, and production of reactive oxygen radicals, Regul Pept 123:51-59, 2004
Reglődi D, Lubics A, Tamás A, Szalontay L, Lengvári I.: Pituitary adenylate cyclase activating polypeptide protects dopaminergic neurons and improves behavioral deficits in a rat model of Parkinson’s disease., Behav Brain Res 151: 303-312, 2004
Boronkai A, Brubel R, Racz B, Tamas A, Kiss P, Horvath G, Lubics A, Szigeti A, Bellyei Sz, Toth G, Lakatos A, Reglodi D: Effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the survival and signal transduction pathways in human choriocarcinoma cells., Ann NY Acad Sci in press, 2008
Roth E, Weber G, Kiss P, Horvath G, Toth G, Gasz B, Ferencz A, Gallyas F, Reglodi D, Racz B: Effects of PACAP and preconditioning against ischemia/reperfusion-induced cardiomyocyte apoptosis in vitro, Ann NY Acad Sci in press, 2008
Atlasz T, Szabadfi K, Reglodi D, Kiss P, Tamas A, Toth G, Molnar A, Szabo K, Gabriel R.: Effects of pituitary adenylate cyclase activating polypeptide (PACAP1-38) and its fragments on retinal degeneration induced by neonatal MSG treatment., Ann NY Acad Sci in press, 2008
Somogyvári-Vigh A, Reglődi D: Pituitary adenylate cyclase activating polypeptide: a potential neuroprotective peptide. Review, Curr Pharm Des 10: 2861-2889, 2004
Tamás A; Lubics A; Szalontay L; Lengvári I; Reglődi D: Age- and gender differences in behavioral and morphological outcome after 6-hydroxydopamine-induced lesion of the substantia nigra in rats, Behav Brain Res 158: 221-229, 2005
Rácz B; Gallyas F Jr; Kiss P; Tóth G; Hegyi O; Gasz B; Borsiczky B; Ferencz A; Rőth E; Tamás A; Lengvári I; Lubics A; Reglődi D: The neuroprotective effects of PACAP in monosodium glutamate-induced retinal lesion involves inhibition of proapoptotic signaling pathways, Regul Pept 137: 20-26, 2006
Reglődi D; Lubics A; Kiss P; Lengvári I; Gaszner B; Tóth G; Hegyi O; Tamás A: Effect of PACAP in 6-OHDA-induced injury of the substantia nigra in intact young and ovariectomized female rats, Neuropeptides 40: 265-274, 2006
Helyes Zs, Pozsgai G, Börzsei R, Németh J, Bagoly T, Márk L, Pintér E, Tóth G, Elekes K, Szolcsányi J, Reglődi D.: Inhibitory effect of PACAP38 on acute neurogenic and non-neurogenic inflammation in the rat, Peptides 28: 1847-1855, 2007
Kiss P, Hauser D, Tamás A, Lubics A, Rácz B, Horváth Zs, Farkas J, Zimmermann F, Stepien A, Lengvári I, Reglődi D.: Changes in open-field activity and novelty-seeking behavior in periadolescent rats neonatally treated with monosodium glutamate., Neurotox Res 12: 85-93, 2007
Rácz B, Gallyas F Jr, Kiss P, Tamás A, Lubics A, Lengvári I, Rőth E, Tóth G, Hegyi O, Verzár Zs, Fabricsek Cs, Reglődi D.: Effects of pituitary adenylate cyclase activating polypeptide (PACAP) on the PKA-Bad-14-3-3 signaling pathway in glutamate-induced retinal injury in neonatal rats., Neurotox Res 12: 95-104, 2007
Rácz B; Gasz B; Borsiczky B; Gallyas F Jr; Tamás A; Józsa R; Lubics A; Kiss P; Rőth E; Ferencz A; Tóth G; Hegyi O; Wittmann I; Lengvári I; Somogyvári-Vigh A; Reglődi D: Protective effects of pituitary adenylate cyclase activating polypeptide in endothelial cells against oxidative stress-induced apoptosis, Gen Comp Endocrinol 153: 115-123, 2007
Rácz B, Gasz B, Gallyas F Jr., Kiss P, Tamás A, Józsa R, Lubics A, Lengvári I, Tóth G, Hegyi O, Rőth E, Reglődi D: PKA-Bad-14-3-3 and Akt-Bad-14-3-3 signaling pathways are involved in the protective effects of PACAP against ischemia/reperfusion-induced cardiomyocyte apoptosis, Regul Pept 145: 105-115, 2008
Atlasz T; Babai N; Kiss P; Reglodi D; Tamas A; Szabadfi K; Toth G; Hegyi O; Lubics A; Gabriel R: Pituitary adenylate cyclase activating polypeptide is protective in bilateral carotid occlusion-induced retinal lesion in rats, Gen Comp Endocrinol 153: 108-114, 2007



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