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Expert Opinion on Drug Discovery Volume 11, 2016 - Issue 2
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Models for erectile dysfunction and their importance to novel drug discovery

Christopher WuMcMaster Institute of Urology, Hamilton, ON, Canada
&
Jason R. KovacMen’s Health Center, Indianapolis, IN, USACorrespondence[email protected]
Pages 185-196 | Received 22 Sep 2015, Accepted 26 Nov 2015, Published online: 22 Dec 2015

References

  • Montorsi F, Adaikan G, Becher E, et al. Summary of the recommendations on sexual dysfunctions in men. J Sex Med. 2010;7:3572–3588.
  • Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts male aging study. J Urol. 1994;151:54–61.

* Results showing the combined prevalence of ED was 52% with complete ED of 15% in men aged 40-70 years. Also confirmed that ED is strongly associated with age and has multiple determinants including some risk factors for vascular disease.

  • Ovid. Amores, 3.7.1-6 in The Love Poems [Internet]. Oxford University Press; 1999.
  • McMahon JM. Paralysin Cave: Impotence, Perception, and Text in the Satyrica of Petronius. Brill; 1997. Mnemosyne Supplements Book 176.
  • Belt E. Leonardo the Florentine (1452-1519). Invest Urol. 1965;3:99–109.
  • Jocelyn HD, Setchell BP:. Regnier de Graaf on the human reproductive organs. An annotated translation of Tractatus de Virorum Organis Generationi Inservientibus (1668) and De Mulierub Organis Generationi Inservientibus Tractatus Novus (1962). J Reprod Fertil Suppl. 1972;17:1–222.
  • Eckhardt C. Untersuchungen uber die erektion des penis beim hund. Beitr Anat Phisiol. 1863;3:123.
  • Brindley GS. Physiology of erection and management of paraplegic infertility. In: Hargreave TB, editor. Male infertility. London: Springer Verlag; 1983. p. 263.
  • Burnett AL, Wesselmann U. History of the neurobiology of the pelvis. Urology. 1999;53:1082–1089.
  • Sachs BD, Bitran D. Spinal block reveals roles for brain and spinal cord in the mediation of reflexive penile erections in rats. Brain Res. 1990;528:99–108.
  • Sachs BD, Ld G. Spinal pacemaker controlling sexual reflexes in male rats. Brain Res. 1979;171:152–156.
  • Hubscher CH, Reed WR, Kaddumi EG, et al. Select spinal lesions reveal multiple ascending pathways in the rat conveying input from the male genitalia. J Physiol. 2010;588:1073–1083.
  • Giuliano F, Rampin O. Neural control of erection. Physiol Behav. 2004;83:189–201.
  • Lewis JE, Walker DF, Beckett SD, et al. Blood pressure within the corpus cavernosum penis of the bull. J Reprod Fertil. 1968;17:155–156.
  • Chung E, De Young L, Gb B. Investigative models in erectile dysfunction: a state-of-the-art review of current animal models. J Sex Med. 2011;8:3291–3305.

* An excelled review that will benefit readers seeking further information on Animal Models.

* Early study documenting the hemodynamics and mechanisms of penile erection.

  • Lue TF, Takamura T, Umraiya M, et al. Hemodynamics of canine corpora cavernosa during erection. Urology. 1984;24:347–352.
  • Trigo-Rocha F, Aronson WJ, Hohenfellner M, et al. Nitric oxide and cGMP: mediators of pelvic nerve-stimulated erection in dogs. Am J Physiol. 1993;264:H419–22.
  • Noto T, Inoue H, Mochida H, et al. Role of adenosine and P2 receptors in the penile tumescence in anesthetized dogs. Eur J Pharmacol. 2001;425:51–55.
  • Takahashi Y, Aboseif SR, Benard F, et al. Effect of intracavernous simultaneous injection of acetylcholine and vasoactive intestinal polypeptide on canine penile erection. J Urol. 1992;148:446–448.
  • Hsu GL, Lin CW, Hsieh CH, et al. Distal ligament in human glans: a comparative study of penile architecture. J Androl. 2005;26:624–628.
  • Hart BL. Sexual reflexes and mating behavior in the male dog. J Comp Physiol Psychol. 1967;64:388–399.
  • Mahley RW, Innerarity TL, Weisgraber KH, et al. Canine hyperlipoproteinemia and atherosclerosis. Accumulation of lipid by aortic medial cells in vivo and in vitro. Am J Pathol. 1977;87:205–226.
  • Aboseif SR, Breza J, Bosch RJ, et al. Local and systemic effects of chronic intracavernous injection of papaverine, prostaglandin E1, and saline in primates. J Urol. 1989;142:403–408.
  • Abozeid M, Juenemann KP, Luo JA, et al. Chronic papaverine treatment: the effect of repeated injections on the simian erectile response and penile tissue. J Urol. 1987;138:1263–1266.
  • Hwang TI, Yang CR, Ho WL, et al. Histopathological change of corpora cavernosa after long-term intracavernous injection. Eur Urol. 1991;20:301–306.
  • Adams MR, Kaplan JR, Koritnik DR, et al. Erectile failure in cynomolgus monkeys with atherosclerosis of the arteries supplying the penis. J Urol. 1984;131:571–573.
  • Faggiotto A, Ross R. Studies of hypercholesterolemia in the nonhuman primate. II. Fatty streak conversion to fibrous plaque. Arteriosclerosis. 1984;4:341–356.

* An early report describing the morphologic changes of chronic, diet induced hypercholestrolemia. Results describing a direct relationship between level and duration of hypercholesterolemia and changes in the artery wall leading to CVD.

  • Williams JK, Anthony MS, Tb C. Coronary heart disease in rhesus monkeys with diet-induced coronary artery atherosclerosis. Arch Pathol Lab Med. 1991;115:784–790.
  • Hellstrom WJG, Wang R, Kadowitz PJ, et al. Potassium channel agonists cause penile erection in cats. Int J Impot Res. 1992;4:35–43.
  • Wang R, Domer FR, Sikka SC, et al. Nitric oxide mediates penile erection in cats. J Urol. 1994;151:234–237.
  • Champion HC, Kadowitz PJ. Nociceptin, an endogenous ligand for the ORL1 receptor, has novel hypotensive activity in the rat [Internet] Life Sci. 1997;60(PL):241–245.
  • Coy H, Champion C, Kadowitz J. of Responses to Adrenomedullin Peptide bed erection employed; 1997.
  • Thielen P, Renders M. Influence of stimulation of sensory nerves of the sacral region on the length of the rabbit penis. Arch Int Physiol Biochim. 1967;75:859–861.
  • Taub HC, Lerner SE, Melman A, et al. Relationship between contraction and relaxation in human and rabbit corpus cavernosum. Urology. 1993;42:698–704.
  • Lin YM, Jsn L. The rabbit as an intracavernous injection study model. Urol Res. 1996;24:27–32.
  • Sullivan ME, Dashwood MR, Thompson CS, et al. Alterations in endothelin B receptor sites in cavernosal tissue of diabetic rabbits: potential relevance to the pathogenesis of erectile dysfunction. J Urol. 1997;158:1966–1972.
  • Bush PA, Aronson WJ, Buga GM, et al. Nitric oxide is a potent relaxant of human and rabbit corpus cavernosum. J Urol. 1992;147:1650–1655.
  • Knispel HH, Goessl C, Beckmann R. Nitric oxide mediates relaxation in rabbit and human corpus cavernosum smooth muscle. Urol Res. 1992;20:253–257.
  • Chang S, Hypolite JA, Changolkar A, et al. Increased contractility of diabetic rabbit corpora smooth muscle in response to endothelin is mediated via Rho-kinase beta. Int J Impot Res. 2003;15:53–62.
  • Lin JS, Lin YM, Jou YC, et al. Role of cyclic adenosine monophosphate in prostaglandin E1-induced penile erection in rabbits. Eur Urol. 1995;28:259–265.
  • Havel RJ, Yamada N, Shames DM. Watanabe heritable hyperlipidemic rabbit. Animal model for familial hypercholesterolemia. Arteriosclerosis. 1989;9:I33–8.
  • Xie D, Kontos CD, Donatucci CF, et al. Cholesterol feeding reduces vascular endothelial growth factor signaling in rabbit corporal tissues. J Sex Med. 2005;2:634–640.
  • Azadzoi KM, Goldstein I, Siroky MB, et al. Mechanisms of ischemia-induced cavernosal smooth muscle relaxation impairment in a rabbit model of vasculogenic erectile dysfunction. J Urol. 1998;160:2216–2222.
  • Dai Q, Silverstein AD, Davies MG, et al. Systemic basic fibroblast growth factor induces favorable histological changes in the corpus cavernosum of hypercholesterolemic rabbits. J Urol. 2003;170:664–668.
  • Henry GD, Byrne R, Hunyh TT, et al. Intracavernosal injections of vascular endothelial growth factor protects endothelial dependent corpora cavernosal smooth muscle relaxation in the hypercholesterolemic rabbit: a preliminary study. Int J Impot Res. 2000;12:334–339.
  • Azadzoi KM, Goldstein I. Erectile dysfunction due to atherosclerotic vascular disease: the development of an animal model. J Urol. 1992;147:1675–1681.

* An early description of the effects of CVD on erectile function in an animal model. This model has been used to further delineate the pathophysiology of ED due to CVD.

  • Sullivan M, Thompson CS, Mikhailidis DP, et al. Differential alterations of prostacyclin, cyclic AMP and cyclic GMP formation in the corpus cavernosum of the diabetic rabbit. Br J Urol. 1998;82:578–584.
  • Beckman JS, Beckman TW, Chen J, et al. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S. 1990;87:1620–1624.
  • Khan MA, Thompson CS, Jeremy JY, et al. The effect of superoxide dismutase on nitric oxide-mediated and electrical field-stimulated diabetic rabbit cavernosal smooth muscle relaxation. BJU Int. 2001;87:98–103.
  • Utkan T, Yildirim MK, Yildirim S, et al. Effects of the specific phosphodiesterase inhibitors on alloxan-induced diabetic rabbit cavernous tissue in vitro. Int J Impot Res. 2001;13:24–30.
  • Melman A. Pathophysiologic basis of erectile dysfunction. What can we learn from animal models? Int J Impot Res. 2001;13:140–142.
  • Kovac JR, Pastuszak AW, Lamb DJ, et al. Testosterone supplementation therapy in the treatment of patients with metabolic syndrome. Postgrad Med. 2014;126:149–156.
  • Beltrán-Sánchez H, Harhay MO, Harhay MM, et al. Prevalence and trends of metabolic syndrome in the adult U.S. population, 1999-2010. J Am Coll Cardiol. 2013;62:697–703.
  • Traish AM, Guay A, Feeley R, et al. The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction. J Androl. 2009;30:10–22.
  • Li YTY, Swales KE, Thomas GJ, et al. Farnesoid X receptor ligands inhibit vascular smooth muscle cell inflammation and migration. Arterioscler Thromb Vasc Biol. 2007;27:2606–2611.
  • Vignozzi L, Morelli A, Filippi S, et al. Farnesoid X receptor activation improves erectile function in animal models of metabolic syndrome and diabetes. J Sex Med. 2011;8:57–77.
  • Vignozzi L, Filippi S, Comeglio P, et al. Nonalcoholic steatohepatitis as a novel player in metabolic syndrome-induced erectile dysfunction: an experimental study in the rabbit [Internet]. Mol Cell Endocrinol. 2014;384:143–154.
  • Quinlan DM, Nelson RJ, Partin AW, et al. The rat as a model for the study of penile erection. J Urol. 1989;141:656–661.
  • Martinez-Pineiro L, Brock G, Trigo-Rocha F, et al. Rat model for the study of penile erection: pharmacologic and electrical-stimulation parameters. Eur Urol. 1994;25:62–70.
  • Kovac J, DeYoung L, Lehmann K, et al. The effects of combined free radical scavenger and sildenafil therapy on age-associated erectile dysfunction: an animal model [Internet]. Urol Ann. 2014;6:314.
  • Hsieh PS, Bochinski DJ, Lin GT, et al. The effect of vascular endothelial growth factor and brain-derived neurotrophic factor on cavernosal nerve regeneration in a nerve-crush rat model. BJU Int. 2003;92:470–475.
  • Yamashita S, Kato R, Kobayashi K, et al. Nerve injury-related erectile dysfunction following nerve-sparing radical prostatectomy: A novel experimental dissection model: original article. Int J Urol. 2009;16:905–911.
  • Mullerad M, Donohue JF, Li PS, et al. Functional sequelae of cavernous nerve injury in the rat: is there model dependency. J Sex Med. 2006;3:77–83.

* A study describing various types of cavernous nerve injury. The authors found no differences in penile hemodynamic alterations from variable forms of cavernous nerve injury. This gave credence to many prior studies that employed multiple different techniques.

  • Burnett AL, Re B. Immunophilin ligands promote penile neurogenesis and erection recovery after cavernous nerve injury. J Urol. 2004;171:495–500.
  • Carrier S, Zvara P, Nunes L, et al. Regeneration of nitric oxide synthase-containing nerves after cavernous nerve neurotomy in the rat. J Urol. 1995;153:1722–1727.
  • Walsh PC, Pj D. Impotence following radical prostatectomy: insight into etiology and prevention. J Urol. 1982;128:492–497.
  • Klein LT, Miller MI, Buttyan R, et al. Apoptosis in the rat penis after penile denervation. J Urol. 1997;158:626–630.
  • Podlasek CA. Sonic hedgehog, apoptosis, and the penis. J Sex Med. 2009;6:334–339.
  • Angeloni N, Bond CW, Harrington D, et al. Sonic hedgehog is neuroprotective in the cavernous nerve with crush injury. J Sex Med. 2013;10:1240–1250.
  • Yuan J, Lin H, Li P, et al. Molecular mechanisms of vacuum therapy in penile rehabilitation: a novel animal study. Eur Urol. 2010;58:773–780.
  • El-Sakka A, Yen TS, Lin CS, et al. Traumatic arteriogenic erectile dysfunction: a rat model. Int J Impot Res. 2001;13:162–171.
  • Lee M-C, El-Sakka AI, Graziottin TM, et al. The effect of vascular endothelial growth factor on a rat model of traumatic arteriogenic erectile dysfunction. J Urol. 2002;167:761–767.
  • Aboseif SR, Breza J, Orvis BR, et al. Erectile response to acute and chronic occlusion of the internal pudendal and penile arteries. J Urol. 1989;141:398–402.
  • Fedele D. Erectile dysfunction in type 1 and type 2 diabetics in Italy. Int J Epidemiol. 2000;29:524–531.
  • Traish AM, Saad F, Guay A:. The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl. 2009;30:23–32.
  • Chitaley K, Luttrell I. Strain differences in susceptibility to in vivo erectile dysfunction following 6 weeks of induced hyperglycemia in the mouse. J Sex Med. 2008;5:1149–1155.
  • Cellek S, Rodrigo J, Lobos E, et al. Selective nitrergic neurodegeneration in diabetes mellitus - a nitric oxide-dependent phenomenon. Br J Pharmacol. 1999;128:1804–1812.
  • Bivalacqua TJ, Usta MF, Kendirci M, et al. Superoxide anion production in the rat penis impairs erectile function in diabetes: influence of in vivo extracellular superoxide dismutase gene therapy. J Sex Med. 2005;2:187–197.
  • Chacko S, Conti MA, Rs A. Effect of phosphorylation of smooth muscle myosin on actin activation and Ca2+ regulation. Proc Natl Acad Sci U S. 1977;74:129–133.

* Early study documenting the basics of penile smooth muscle physiology.

  • Feng J, Ito M, Ichikawa K, et al. Inhibitory phosphorylation site for Rho associated kinase on smooth muscle myosin phosphatase. J Biol Chem. 1999;274:37385–37390.
  • Mills TM, Chitaley K, Wingard CJ, et al. Effect of Rho-kinase inhibition on vasoconstriction in the penile circulation. J Appl Physiol. 2001;91:1269–1273.
  • Bivalacqua TJ, Champion HC, Usta MF, et al. RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction. Proc Natl Acad Sci U S. 2004;101:9121–9126.
  • Luttrell IP, Swee M, Starcher B, et al. Erectile dysfunction in the type II diabetic db/db mouse : impaired venoocclusion with altered cavernosal vasoreactivity and matrix . Am J Physiol Heart Circ Physiol. 2008;294(5):H2204–H2211.
  • Kovanecz I, Nolazco G, Ferrini MG, et al. Early onset of fibrosis within the arterial media in a rat model of type 2 diabetes mellitus with erectile dysfunction [Internet]. BJU Int. 2009;103:1396–1404.
  • Kovanecz I, Ferrini MG, Vernet D, et al. Pioglitazone prevents corporal veno-occlusive dysfunction in a rat model of type 2 diabetes mellitus. BJU Int. 2006;98:116–124.
  • Lasker GF, Pankey EA, Frink TJ, et al. The sGC activator BAY 60-2770 has potent erectile activity in the rat. Am J Physiol Hear Circ Physiol. 2013;304:H1670–H1679.
  • Ferrini MG, Kovanecz I, Sanchez S, et al. Fibrosis and loss of smooth muscle in the corpora cavernosa precede corporal veno-occlusive dysfunction (CVOD) induced by experimental cavernosal nerve damage in the rat. J Sex Med. 2009;6:415–428.
  • Rambhatla A, Kovanecz I, Ferrini M, et al. Rationale for phosphodiesterase 5 inhibitor use post-radical prostatectomy: experimental and clinical review. Int J Impot Res. 2008;20:30–34.
  • Kovanecz I, Rambhatla A, Ferrini M, et al. Long-term continuous sildenafil treatment ameliorates corporal veno-occlusive dysfunction (CVOD) induced by cavernosal nerve resection in rats. Int J Impot Res. 2008;20:202–212.
  • Kovanecz I, Rambhatla A, Ferrini M, et al. Chronic daily tadalafil prevents the corporal fibrosis and veno-occlusive dysfunction that occurs after cavernosal nerve resection. BJU Int. 2008;101:203–210.
  • Hatzimouratidis K, Burnett AL, Hatzichristou D, et al. Phosphodiesterase type 5 inhibitors in postprostatectomy erectile dysfunction: a critical analysis of the basic science rationale and clinical application. Eur Urol. 2009;55:334–347.

* An analysis of the role of PDE5i in post-prostatectomy ED suggesting that in humans, the roles of PDE5i alone as a rehabilitation strategy were unclear.

  • Fusco F, Razzoli E, Imbimbo C, et al. A new era in the treatment of erectile dysfunction: chronic phosphodiesterase type 5 inhibition. BJU Int. 2010;105:1634–1639.
  • Lin CS, Xin ZC, Deng CH, et al. Recent advances in andrology-related stem cell research. Asian J Androl. 2008;10:171–175.
  • Lin CS, Xin ZC, Wang Z, et al. Stem cell therapy for erectile dysfunction: a critical review. Stem Cells Dev. 2012;21:343–351. * An excellent reivew on stem cell therapy in the treatment of ED.
  • Deng W, Bivalacqua TJ, Chattergoon NN, et al. Adenoviral gene transfer of eNOS: high-level expression in ex vivo expanded marrow stromal cells. Am J Physiol Cell Physiol. 2003;285:C1322–C1329.
  • Song YS, Lee HJ, Park IH, et al. Potential differentiation of human mesenchymal stem cell transplanted in rat corpus cavernosum toward endothelial or smooth muscle cells. Int J Impot Res. 2007;19:378–385.
  • Nolazco G, Kovanecz I, Vernet D, et al. Effect of muscle-derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat. BJU Int. 2008;101:1156–1164.
  • Fall PA, Izikki M, Tu L, et al. Apoptosis and effects of intracavernous bone marrow cell injection in a rat model of postprostatectomy erectile dysfunction. Eur Urol. 2009;56:716–726.
  • Garcia MM, Fandel TM, Lin G, et al. Treatment of erectile dysfunction in the obese type 2 diabetic ZDF rat with adipose tissue-derived stem cells. J Sex Med. 2010;7:89–98.
  • Albersen M, Fandel TM, Lin G, et al. Injections of adipose tissue-derived stem cells and stem cell lysate improve recovery of erectile function in a rat model of cavernous nerve injury. J Sex Med. 2010;7:3331–3340.
  • Lin G, Qiu X, Fandel T, et al. Tracking intracavernously injected adipose-derived stem cells to bone marrow [Internet]. Int J Impot Res. 2011;23:268–275.
  • Fandel TM, Albersen M, Lin G, et al. Recruitment of intracavernously injected adipose-derived stem cells to the major pelvic ganglion improves erectile function in a rat model of cavernous nerve injury. Eur Urol. 2012;61:201–210.
  • Williams JK, Andersson KE, Christ G. Animal models of erectile dysfunction (ED): potential utility of non-human primates as a model of atherosclerosis-induced vascular ED [Internet]. Int J Impot Res. 2012;24:91–100.
  • Sachs BD. Erection evoked in male rats by airborne scent from estrous females. Physiol Behav. 1997;62:921–924.
  • Andrus SB, Fillios LC, Mann GV, et al. Experimental production of gross atherosclerosis in the rat. J Exp Med. 1956;104:539–554.
  • Barter PJ, Lally JI. The activity of an esterified cholesterol transferring factor in human and rat serum. Biochim Biophys Acta. 1978;531:233–236.
  • Ziegler MA, Distasi MR, Bills RG, et al. Marvels, mysteries, and misconceptions of vascular compensation to peripheral artery occlusion. Microcirculation. 2010;17:3–20.
  • Burnett AL, Nelson RJ, Calvin DC, et al. Nitric oxide-dependent penile erection in mice lacking neuronal nitric oxide synthase. Mol Med. 1996;2:288–296.
  • Gocmen C, Ucar P, Singirik E, et al. An in vitro study of nonadrenergic-noncholinergic activity on the cavernous tissue of mouse. Urol Res. 1997;25:269–275.
  • Mizusawa H, Hedlund P, Håkansson A, et al. Morphological and functional in vitro and in vivo characterization of the mouse corpus cavernosum. Br J Pharmacol. 2001;132:1333–1341.
  • Plump AS, Smith JD, Hayek T, et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell. 1992;71:343–353.
  • Nakashima Y, Plump AS, Raines EW, et al. the arterial tree. Arteriosclerosis. 1994. DOI:10.1161/01.ATV.14.1.133.
  • d’Uscio LV, Baker TA, Mantilla CB, et al. Mechanism of endothelial dysfunction in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2001;21:1017–1022.
  • Xie D, Odronic SI, Wu F, et al. A mouse model of hypercholesterolemia-induced erectile dysfunction. J Sex Med. 2007;4:898–907.
  • Ifergan I, Kebir H, Terouz S, et al. Role of ninjurin-1 in the migration of myeloid cells to central nervous system inflammatory lesions. Ann Neurol. 2011;70:751–763.
  • Araki T, Milbrandt J. Ninjurin, a novel adhesion molecule, is induced by nerve injury and promotes axonal growth. Neuron. 1996;17:353–361.
  • Lee HJ, Ahn BJ, Shin MW, et al. Ninjurin1 mediates macrophage-induced programmed cell death during early ocular development [Internet]. Cell Death Differ. 2009;16:1395–1407.
  • Kim DK, Yin GN, Ryu JK, et al. Differential expression of nerve injury-induced protein 1 (Ninjurin 1) in in vivo and in vitro models for diabetic erectile dysfunction. Korean J Urol. 2012;53:636–642.
  • Yin GN, Choi MJ, Kim WJ, et al. Inhibition of Ninjurin 1 restores erectile function through dual angiogenic and neurotrophic effects in the diabetic mouse [Internet]. Proc Natl Acad Sci U S. 2014;111:E2731–40.
  • Yin GN, Kim WJ, Jin HR, et al. Nerve injury-induced protein 1 (Ninjurin-1) is a novel therapeutic target for cavernous nerve injury-induced erectile dysfunction in mice. J Sex Med. 2013;10:1488–1501.

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