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2-Aminoetoksidifenil Borat’ ın Akut Serebral İskemi-Reperfüzyon Hasarı Üzerindeki Etkisi; Deneysel Bir Çalışma

Yıl 2020, , 74 - 81, 16.03.2020
https://doi.org/10.31832/smj.637779

Öz















Amaç: Serebral İ/R hasarında hücre ölümüne neden olan faktörlerin
başında hücre içi kalsiyum konsantrasyonundaki artış gelmektedir. Depo
kontrollü Ca2+  girişi (Store
operated Ca2+
entry,
SOCE
), hücre içine Ca2+ girişinden sorumludur ve Orai1, STIM1 ve
STIM2 proteinleri aracılığıyla gerçekleşir. 2
-Aminoetoksidifenil Borat (2-APB), hücreye depo kontrollü Ca2+
girişini engelleyen kimyasal bir ajandır. Bu çalışmada deneysel olarak sıçanlarda oluşturulan serebral İ/R
modelinde meydana gelen hasarda
2-APB’nin
olası
koruyucu etkisi araştırıldı.




Gereç ve Yöntemler: Çalışmada, on sekiz erkek sıçan 3 gruba ayrıldı (n=6). Sham
grubunda
cerrahi prosedür
uygulandı ancak İ/R modeli oluşturulmadı.
Sİ/R ve Sİ/R-2APB grubundaki sıçanlara
akut serebral
İ/R modeli oluşturuldu.
Bir saatl sonra reperfüzyon sağlandı. Sİ/R-2APB grubundaki sıçanlara
reperfüzyondan 10 dk önce 2-APB uygulandı. Reperfüzyondan 3
saat sonra
sıçanlara ötenazi uygulanarak beyinleri
çıkarıldı.
Sıçan beyin dokularında
meydana gelen değişiklikler histokimyasal yöntemlerle,
TUNEL metoduyla ve immünohistokimyasal
olarak değerlendirildi.




Bulgular: Sİ/R grubunda, sham
grubuna kıyasla
histolojik yapının
bozulduğu, apopitozisin ve
Orai1, STIM1 ve STIM2 proteinlerinin ekspresyonunun arttığı belirlendi. 2-APB  uygulanan grupta ise doku hasarının ve apopitotik hücrelerin azaldığı, Orai1, STIM1 ve STIM2 ifadesinin belirgin şekilde inhibe edildiği ortaya konuldu.




Sonuç: Sonuç olarak,
serebral İ/R hasarlı dokuda
2-APB’nin
hücreye SOCE aracılı
Ca2+  girişini azaltarak apopitozun ve nöronal
hasarın azatılmasında etkili olabileceği ortaya konuldu.








Kaynakça

  • Pei Z, Ho HT, Cheung RT. Pre-treatment with melatonin reduces volume of cerebral infarction in a permanent middle cerebral artery occlusion stroke model in the rat. Neurosci Lett 2002; 318: 141-4.
  • Matsuo Y, et al. Role of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in the rat. Brain Res 1994; 656: 344-52.
  • Lerouet D, Beray-Berthat V, Palmier B, Plotkine M, Margaill I. Changes in oxidative stress, iNOS activity and neutrophil infiltration in severe transient focal cerebral ischemia in rats. Brain Res 2002; 958: 166-75.
  • Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 2012; 298: 229-317.
  • Cuzzocrea S, Riley DP, Caputi AP, Salvemini D. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol Rev 2001; 53: 135-59.
  • Farber JL. The role of calcium in lethal cell injury. Chem Res Toxicol 1990; 3: 503-8.
  • Berridge MJ. The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium 2002; 32: 235-49.
  • Putney JW, Jr. Recent breakthroughs in the molecular mechanism of capacitative calcium entry (with thoughts on how we got here). Cell Calcium 2007; 42: 103-10.
  • Putney JW. Capacitative calcium entry: from concept to molecules. Immunol Rev 2009; 231: 10-22.
  • Cahalan MD. STIMulating store-operated Ca(2+) entry. Nat Cell Biol 2009; 11: 669-77.
  • Liao Y, et al. Functional interactions among Orai1, TRPCs, and STIM1 suggest a STIM-regulated heteromeric Orai/TRPC model for SOCE/Icrac channels. Proc Natl Acad Sci U S A 2008; 105: 2895-900.
  • Kim MS, et al. Native Store-operated Ca2+ Influx Requires the Channel Function of Orai1 and TRPC1. J Biol Chem 2009; 284: 9733-41.
  • Liao Y, et al. Orai proteins interact with TRPC channels and confer responsiveness to store depletion. Proc Natl Acad Sci U S A 2007; 104: 4682-7.
  • Liao Y, et al. A role for Orai in TRPC-mediated Ca2+ entry suggests that a TRPC:Orai complex may mediate store and receptor operated Ca2+ entry. Proc Natl Acad Sci U S A 2009; 106: 3202-6.
  • Zhang M, et al. Suppression of STIM1 in the early stage after global ischemia attenuates the injury of delayed neuronal death by inhibiting store-operated calcium entry-induced apoptosis in rats. Neuroreport 2014; 25: 507-13.
  • Kaur C, Foulds WS, Ling EA. Hypoxia-ischemia and retinal ganglion cell damage. Clin Ophthalmol 2008; 2: 879-89.
  • Janaky M, Grosz A, Toth E, Benedek K, Benedek G. Hypobaric hypoxia reduces the amplitude of oscillatory potentials in the human ERG. Doc Ophthalmol 2007; 114: 45-51.
  • Tinjust D, Kergoat H, Lovasik JV. Neuroretinal function during mild systemic hypoxia. Aviat Space Environ Med 2002; 73: 1189-94.
  • Chen Y, et al. LLDT-8 protects against cerebral ischemia/reperfusion injury by suppressing post-stroke inflammation. Journal of pharmacological sciences 2016; 131: 131-37.
  • Bonova P, Burda J, Danielisova V, Nemethova M, Gottlieb M. Delayed post-conditioning reduces post-ischemic glutamate level and improves protein synthesis in brain. Neurochemistry international 2013; 62: 854-60.
  • Bederson JB, et al. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. stroke 1986; 17: 472-76.
  • Yanık B, Görgülü A, Kırış T, Çobanoğlu S. Fokal Serebral İskemi-Reperfüzyon Modelinde Nimodipin Ve Memantin'in Etkileri.
  • Hei Y, et al. Neuregulin1 attenuates cognitive deficits and hippocampal CA1 neuronal apoptosis partly via ErbB4 receptor in a rat model of chronic cerebral hypoperfusion. Behavioural brain research 2019; 365: 141-49.
  • Chen G, Shi J, Hu Z, Hang C. Inhibitory effect on cerebral inflammatory response following traumatic brain injury in rats: a potential neuroprotective mechanism of N-acetylcysteine. Mediators of inflammation 2008; 2008.
  • Fedchenko N, Reifenrath J. Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue - a review. Diagn Pathol 2014; 9: 221.
  • Demir R, et al. Genç İskemik Stroklu Hastalarda Protrombotik Gen Polimorfizmleri ve Strok Risk Faktörlerinin Belirlenmesi. Sakarya Tıp Dergisi 2014; 4: 119-24.
  • Kavaklı A, Acet A, Parlakpınar H, Akpolat N, Şahna A. Ratlarda beyin İskemi-reperfüzyonu sonucu oluşan morfolojik değişikliklere melatonin ve pinealektominin etkisi. FÜ Sağ. Bil. Derg 2007; 21: 63-66.
  • Vercesi AE, Kowaltowski AJ, Oliveira HC, Castilho RF. Mitochondrial Ca2+ transport, permeability transition and oxidative stress in cell death: implications in cardiotoxicity, neurodegeneration and dyslipidemias. Front Biosci 2006; 11: 2554-64.
  • Trocha M, Szelag A. The role of calcium and calcium channel blocking drugs in damage to the liver preserved for transplantation. Ann Transplant 2004; 9: 5-11.
  • Victor M, Ropper AH, Adams RD. Adams and Victor's principles of neurology. Baskı. 2001.
  • Warlow C, et al. Preventing recurrent stroke and other serious vascular events. Stroke: a practical guide to management 2001: 653-722.
  • Ataş E, et al. Deneysel Serebral İskemi-Reperfüzyon Hasarında Bosentanın Koruyucu Etkisi. Türk Beyin Damar Hastalıkları Dergisi 2013; 19: 46-50.
  • Secondo A, et al. ORAI1/STIM1 Interaction Intervenes in Stroke and in Neuroprotection Induced by Ischemic Preconditioning Through Store-Operated Calcium Entry. stroke 2019; 50: 1240-49.
  • Sagsoz N, Kisa U, Apan A. Ischaemia-reperfusion injury of rat ovary and the effects of vitamin C, mannitol and verapamil. Hum Reprod 2002; 17: 2972-6.
  • Taskin MI, et al. Effect of 2-aminoethoxydiphenyl borate on ischemia-reperfusion injury in a rat ovary model. Eur J Obstet Gynecol Reprod Biol 2014; 178: 74-9.
  • Nicoud IB, et al. 2-APB protects against liver ischemia-reperfusion injury by reducing cellular and mitochondrial calcium uptake. Am J Physiol Gastrointest Liver Physiol 2007; 293: G623-30.
  • Yildar M, et al. Protective effect of 2-aminoethyl diphenylborinate on acute ischemia-reperfusion injury in the rat kidney. J Surg Res 2014; 187: 683-9.
  • Sari E, et al. Protective effect of 2-APB on testicular ischemia-reperfusion injury in rats. J Urol 2015; 193: 1036-41.
  • Kaymakci M, et al. The Potential Protective Effects of 2-aminoethyl Diphenylborinate against Inner Ear Acoustic Trauma: Experimental Study Using Transmission and Scanning Electron Microscopy. J Int Adv Otol 2015; 11: 1-5.
  • DeHaven WI, Smyth JT, Boyles RR, Bird GS, Putney JW, Jr. Complex actions of 2-aminoethyldiphenyl borate on store-operated calcium entry. J Biol Chem 2008; 283: 19265-73.
  • . Yang ML, Tao T, Xu J, Liu Z, Xu D. Antiapoptotic Effect of Gene Therapy with Recombinant Adenovirus Vector Containing Hypoxia-inducible Factor-1alpha after Cerebral Ischemia and Reperfusion in Rats. Chin Med J (Engl) 2017; 130: 1700-06.
  • Dimopoulos C, et al. Expression of S100B Protein in Ischemia/Reperfusion-Induced Brain Injury After Cyclosporine Therapy: A Biochemical Serum Marker with Prognostic Value? Med Sci Monit 2019; 25: 1637-44.
  • Wan J, et al. Protective effect of Danhong Injection combined with Naoxintong Capsule on cerebral ischemia-reperfusion injury in rats. J Ethnopharmacol 2018; 211: 348-57.
  • Lorrio S, Negredo P, Roda JM, Garcia AG, Lopez MG. Effects of memantine and galantamine given separately or in association, on memory and hippocampal neuronal loss after transient global cerebral ischemia in gerbils. Brain Res 2009; 1254: 128-37.
  • Kressel M, Groscurth P. Distinction of apoptotic and necrotic cell death by in situ labelling of fragmented DNA. Cell Tissue Res 1994; 278: 549-56.
  • Osborne NN, et al. Retinal ischemia: mechanisms of damage and potential therapeutic strategies. Prog Retin Eye Res 2004; 23: 91-147.
  • Emptage NJ, Reid CA, Fine A. Calcium stores in hippocampal synaptic boutons mediate short-term plasticity, store-operated Ca2+ entry, and spontaneous transmitter release. Neuron 2001; 29: 197-208.
  • Baba A, et al. Activity-evoked capacitative Ca2+ entry: implications in synaptic plasticity. J Neurosci 2003; 23: 7737-41.
  • Kraft R. STIM and ORAI proteins in the nervous system. Channels (Austin) 2015; 9: 245-52.

Effect of 2-Aminoethoxydiphenyl Borate on Acute Cerebral Ischemia-Reperfusion Injury; An Experimental Study

Yıl 2020, , 74 - 81, 16.03.2020
https://doi.org/10.31832/smj.637779

Öz















Objective: The store-operated Ca2+ entry (SOCE) is
responsible for
Ca2+ entry into the cell and takes place mediated by the Orai1, STIM1, and
STIM2 proteins. 2-Aminoethoxydiphenyl Borate (2-APB) is a chemical agent that
prevents store-operated
Ca2+ entry into the cell. In this study, it was investigated the possible
protective effect of 2-APB on the occurred injury in the experimental cerebral
I/R model in rats.




Materials and Methods:
In the study, eighteen male rats were
divided into three groups (n=6). In the Sham group, only
surgical procedure was
applied without I/R model. Acute cerebral I/R model was created for rats in the
SI/R and SI/R-2APB groups. Reperfusion was realized one-hour later. Ten-minutes
before reperfusion, 2-APB was administered to the rats in the SI/R-2APB group.
After three hours of reperfusion, the rats were sacrificed and their brains
were removed. The changes that occurred in the brain tissues were investigated
by using histochemical methods, the TUNEL, and immunohistochemical staining.




Results: In the SI/R group, it was determined that the
histological structure was impaired and apoptosis and expression of Orai1,
STIM1, and STIM2 proteins were increased compared to the sham group. In the
2-APB administrated group, it was revealed that the tissue damage and apoptotic
cells were decreased, and Orai1, STIM1, and STIM2 expression were significantly
inhibited.




Conclusion: As a result, it has been demonstrated that 2-APB
may be effective in decreasing apoptosis and neuronal damage by reducing
SOCE-mediated
Ca2+ influx into the cell in cerebral I/R damaged
tissue.








Kaynakça

  • Pei Z, Ho HT, Cheung RT. Pre-treatment with melatonin reduces volume of cerebral infarction in a permanent middle cerebral artery occlusion stroke model in the rat. Neurosci Lett 2002; 318: 141-4.
  • Matsuo Y, et al. Role of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in the rat. Brain Res 1994; 656: 344-52.
  • Lerouet D, Beray-Berthat V, Palmier B, Plotkine M, Margaill I. Changes in oxidative stress, iNOS activity and neutrophil infiltration in severe transient focal cerebral ischemia in rats. Brain Res 2002; 958: 166-75.
  • Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 2012; 298: 229-317.
  • Cuzzocrea S, Riley DP, Caputi AP, Salvemini D. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol Rev 2001; 53: 135-59.
  • Farber JL. The role of calcium in lethal cell injury. Chem Res Toxicol 1990; 3: 503-8.
  • Berridge MJ. The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium 2002; 32: 235-49.
  • Putney JW, Jr. Recent breakthroughs in the molecular mechanism of capacitative calcium entry (with thoughts on how we got here). Cell Calcium 2007; 42: 103-10.
  • Putney JW. Capacitative calcium entry: from concept to molecules. Immunol Rev 2009; 231: 10-22.
  • Cahalan MD. STIMulating store-operated Ca(2+) entry. Nat Cell Biol 2009; 11: 669-77.
  • Liao Y, et al. Functional interactions among Orai1, TRPCs, and STIM1 suggest a STIM-regulated heteromeric Orai/TRPC model for SOCE/Icrac channels. Proc Natl Acad Sci U S A 2008; 105: 2895-900.
  • Kim MS, et al. Native Store-operated Ca2+ Influx Requires the Channel Function of Orai1 and TRPC1. J Biol Chem 2009; 284: 9733-41.
  • Liao Y, et al. Orai proteins interact with TRPC channels and confer responsiveness to store depletion. Proc Natl Acad Sci U S A 2007; 104: 4682-7.
  • Liao Y, et al. A role for Orai in TRPC-mediated Ca2+ entry suggests that a TRPC:Orai complex may mediate store and receptor operated Ca2+ entry. Proc Natl Acad Sci U S A 2009; 106: 3202-6.
  • Zhang M, et al. Suppression of STIM1 in the early stage after global ischemia attenuates the injury of delayed neuronal death by inhibiting store-operated calcium entry-induced apoptosis in rats. Neuroreport 2014; 25: 507-13.
  • Kaur C, Foulds WS, Ling EA. Hypoxia-ischemia and retinal ganglion cell damage. Clin Ophthalmol 2008; 2: 879-89.
  • Janaky M, Grosz A, Toth E, Benedek K, Benedek G. Hypobaric hypoxia reduces the amplitude of oscillatory potentials in the human ERG. Doc Ophthalmol 2007; 114: 45-51.
  • Tinjust D, Kergoat H, Lovasik JV. Neuroretinal function during mild systemic hypoxia. Aviat Space Environ Med 2002; 73: 1189-94.
  • Chen Y, et al. LLDT-8 protects against cerebral ischemia/reperfusion injury by suppressing post-stroke inflammation. Journal of pharmacological sciences 2016; 131: 131-37.
  • Bonova P, Burda J, Danielisova V, Nemethova M, Gottlieb M. Delayed post-conditioning reduces post-ischemic glutamate level and improves protein synthesis in brain. Neurochemistry international 2013; 62: 854-60.
  • Bederson JB, et al. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. stroke 1986; 17: 472-76.
  • Yanık B, Görgülü A, Kırış T, Çobanoğlu S. Fokal Serebral İskemi-Reperfüzyon Modelinde Nimodipin Ve Memantin'in Etkileri.
  • Hei Y, et al. Neuregulin1 attenuates cognitive deficits and hippocampal CA1 neuronal apoptosis partly via ErbB4 receptor in a rat model of chronic cerebral hypoperfusion. Behavioural brain research 2019; 365: 141-49.
  • Chen G, Shi J, Hu Z, Hang C. Inhibitory effect on cerebral inflammatory response following traumatic brain injury in rats: a potential neuroprotective mechanism of N-acetylcysteine. Mediators of inflammation 2008; 2008.
  • Fedchenko N, Reifenrath J. Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue - a review. Diagn Pathol 2014; 9: 221.
  • Demir R, et al. Genç İskemik Stroklu Hastalarda Protrombotik Gen Polimorfizmleri ve Strok Risk Faktörlerinin Belirlenmesi. Sakarya Tıp Dergisi 2014; 4: 119-24.
  • Kavaklı A, Acet A, Parlakpınar H, Akpolat N, Şahna A. Ratlarda beyin İskemi-reperfüzyonu sonucu oluşan morfolojik değişikliklere melatonin ve pinealektominin etkisi. FÜ Sağ. Bil. Derg 2007; 21: 63-66.
  • Vercesi AE, Kowaltowski AJ, Oliveira HC, Castilho RF. Mitochondrial Ca2+ transport, permeability transition and oxidative stress in cell death: implications in cardiotoxicity, neurodegeneration and dyslipidemias. Front Biosci 2006; 11: 2554-64.
  • Trocha M, Szelag A. The role of calcium and calcium channel blocking drugs in damage to the liver preserved for transplantation. Ann Transplant 2004; 9: 5-11.
  • Victor M, Ropper AH, Adams RD. Adams and Victor's principles of neurology. Baskı. 2001.
  • Warlow C, et al. Preventing recurrent stroke and other serious vascular events. Stroke: a practical guide to management 2001: 653-722.
  • Ataş E, et al. Deneysel Serebral İskemi-Reperfüzyon Hasarında Bosentanın Koruyucu Etkisi. Türk Beyin Damar Hastalıkları Dergisi 2013; 19: 46-50.
  • Secondo A, et al. ORAI1/STIM1 Interaction Intervenes in Stroke and in Neuroprotection Induced by Ischemic Preconditioning Through Store-Operated Calcium Entry. stroke 2019; 50: 1240-49.
  • Sagsoz N, Kisa U, Apan A. Ischaemia-reperfusion injury of rat ovary and the effects of vitamin C, mannitol and verapamil. Hum Reprod 2002; 17: 2972-6.
  • Taskin MI, et al. Effect of 2-aminoethoxydiphenyl borate on ischemia-reperfusion injury in a rat ovary model. Eur J Obstet Gynecol Reprod Biol 2014; 178: 74-9.
  • Nicoud IB, et al. 2-APB protects against liver ischemia-reperfusion injury by reducing cellular and mitochondrial calcium uptake. Am J Physiol Gastrointest Liver Physiol 2007; 293: G623-30.
  • Yildar M, et al. Protective effect of 2-aminoethyl diphenylborinate on acute ischemia-reperfusion injury in the rat kidney. J Surg Res 2014; 187: 683-9.
  • Sari E, et al. Protective effect of 2-APB on testicular ischemia-reperfusion injury in rats. J Urol 2015; 193: 1036-41.
  • Kaymakci M, et al. The Potential Protective Effects of 2-aminoethyl Diphenylborinate against Inner Ear Acoustic Trauma: Experimental Study Using Transmission and Scanning Electron Microscopy. J Int Adv Otol 2015; 11: 1-5.
  • DeHaven WI, Smyth JT, Boyles RR, Bird GS, Putney JW, Jr. Complex actions of 2-aminoethyldiphenyl borate on store-operated calcium entry. J Biol Chem 2008; 283: 19265-73.
  • . Yang ML, Tao T, Xu J, Liu Z, Xu D. Antiapoptotic Effect of Gene Therapy with Recombinant Adenovirus Vector Containing Hypoxia-inducible Factor-1alpha after Cerebral Ischemia and Reperfusion in Rats. Chin Med J (Engl) 2017; 130: 1700-06.
  • Dimopoulos C, et al. Expression of S100B Protein in Ischemia/Reperfusion-Induced Brain Injury After Cyclosporine Therapy: A Biochemical Serum Marker with Prognostic Value? Med Sci Monit 2019; 25: 1637-44.
  • Wan J, et al. Protective effect of Danhong Injection combined with Naoxintong Capsule on cerebral ischemia-reperfusion injury in rats. J Ethnopharmacol 2018; 211: 348-57.
  • Lorrio S, Negredo P, Roda JM, Garcia AG, Lopez MG. Effects of memantine and galantamine given separately or in association, on memory and hippocampal neuronal loss after transient global cerebral ischemia in gerbils. Brain Res 2009; 1254: 128-37.
  • Kressel M, Groscurth P. Distinction of apoptotic and necrotic cell death by in situ labelling of fragmented DNA. Cell Tissue Res 1994; 278: 549-56.
  • Osborne NN, et al. Retinal ischemia: mechanisms of damage and potential therapeutic strategies. Prog Retin Eye Res 2004; 23: 91-147.
  • Emptage NJ, Reid CA, Fine A. Calcium stores in hippocampal synaptic boutons mediate short-term plasticity, store-operated Ca2+ entry, and spontaneous transmitter release. Neuron 2001; 29: 197-208.
  • Baba A, et al. Activity-evoked capacitative Ca2+ entry: implications in synaptic plasticity. J Neurosci 2003; 23: 7737-41.
  • Kraft R. STIM and ORAI proteins in the nervous system. Channels (Austin) 2015; 9: 245-52.
Toplam 49 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm Makaleler
Yazarlar

Tuba Demirci 0000-0002-8814-9648

Nuray Bilge Bilge 0000-0002-9328-1678

Özlem Özgül Abuç 0000-0001-9852-8839

Nuh Çağrı Karaavcı Bu kişi benim 0000-0002-4316-3614

Yayımlanma Tarihi 16 Mart 2020
Gönderilme Tarihi 24 Ekim 2019
Yayımlandığı Sayı Yıl 2020

Kaynak Göster

AMA Demirci T, Bilge NB, Özgül Abuç Ö, Karaavcı NÇ. 2-Aminoetoksidifenil Borat’ ın Akut Serebral İskemi-Reperfüzyon Hasarı Üzerindeki Etkisi; Deneysel Bir Çalışma. Sakarya Tıp Dergisi. Mart 2020;10(1):74-81. doi:10.31832/smj.637779

30703

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