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Central Nervous System Agents in Medicinal Chemistry

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ISSN (Print): 1871-5249
ISSN (Online): 1875-6166

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Research Article

Potential Mechanisms Involved in the Anticonvulsant Effect of Methanol Extract of Pyrenancantha staudtii in Mice

Author(s): Olayemi K. Wakeel*, Oluropo B. Awosan, Oyetunji T. Kolawole, Akeem A. Ayankunle, Olukunle J. Onaolapo and Oluwaseyi A. Adeyeba

Volume 20, Issue 2, 2020

Page: [144 - 154] Pages: 11

DOI: 10.2174/1871524920666200211113633

Price: $65

Abstract

Objective: To determine the potential effect of Pyrenancantha staudtii extract on experimentally induced seizures in mice and to evaluate the role of benzodiazepines, naloxone, and serotonin within these pathways.

Methods: Animal behaviours were evaluated using open field, hexobarbitone-induced sleep model, and anticonvulsant activity using picrotoxin-, or strychnine-, or isoniazid-induced convulsions. Attempt to understand the mode of action of the anticonvulsant activity of the plant, three notable antagonists (flumazenil, 3 mg/kg; naloxone 5 mg/kg, i.p., and cyproheptadine, 4 mg/kg, i.p) were used.

Results: The results revealed a significant (p < 0.05) reduction in the frequency of rearing and grooming episodes compared with the control. The extract of P. staudtii potentiates the sleeping time of hexobarbitone-induced hypnosis in a dose-related manner. P. staudtii stem bark extracts significantly (p<0.05) prolonged the onset of a seizure and attenuated the duration of seizure in a dose-dependent manner in picrotoxin- and or isoniazid-induced seizures. While, P. staudtii stem bark extract at all doses (100, 200, and 400 mg kg-1) though significantly prolonged the onset of action, but did not confer any significant changes on the duration, as well as mortality in this strychnine-induced seizure model. However, the anticonvulsant activity of the methanolic extract of P. staudtii was significantly reversed following intraperitoneal pre-treatment with flumazenil (GABA receptor antagonist) and naloxone (opioid receptor antagonist) but not cyproheptadine (5-HT2 receptor antagonist) in picrotoxin-induced convulsion.

Conclusion: The data obtained suggest that methanol extract of P. staudtii possessed significant anticonvulsant effect, thereby confirming the traditional uses of P. staudtii in the treatment of epilepsy; mechanisms of which could involve the interaction with GABAergic and or opioidergic system.

Keywords: Pyrenancantha staudtii, picrotoxin, isoniazid, cyproheptadine, hexobarbitone, strychnine.

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[1]
Vyawahare, N.S.; Khandelwal, A.R.; Batra, V.R.; Nikam, A.P. Herbal anticonvulsants. J. Herbal Med. Toxicol., 2007, 1(1), 9-14.
[2]
Kolawole, O.T.; Akiibinu, M.O.; Ayankunle, A.A. Anticonvulsant and depressant activity of methanol leaf extract of Croton zambesicus. Int. J. Trop. Dis. Health, 2012, 2(1), 33-41.
[http://dx.doi.org/10.9734/IJTDH/2012/1043]
[3]
Sharma, S.; Sankhyan, N.; Ramesh, K.; Gulati, S. Child neurology: Epilepsy of infancy with migrating focal seizures. Neurology, 2011, 77(4), e21-e24.
[http://dx.doi.org/10.1212/WNL.0b013e3182267b4f] [PMID: 21788614]
[4]
Clinckers, R.; Smolders, I.; Meurs, A.; Ebinger, G.; Michotte, Y. Hippocampal dopamine and serotonin elevations as pharmacodynamic markers for the anticonvulsant efficacy of oxcarbazepine and 10,11-dihydro-10-hydroxycarbamazepine. Neurosci. Lett., 2005, 390(1), 48-53.
[http://dx.doi.org/10.1016/j.neulet.2005.07.049] [PMID: 16139430]
[5]
Schachter, S.C. Botanicals and herbs: A traditional approach to treating epilepsy. Neurotherapeutics, 2009, 6(2), 415-420.
[http://dx.doi.org/10.1016/j.nurt.2008.12.004] [PMID: 19332338]
[6]
Soltis, D.E.; Smith, S.A.; Cellinese, N.; Wurdack, K.J.; Tank, D.C.; Brockington, S.F.; Refulio-Rodriguez, N.F.; Walker, J.B.; Moore, M.J.; Carlsward, B.S.; Bell, C.D.; Latvis, M.; Crawley, S.; Black, C.; Diouf, D.; Xi, Z.; Rushworth, C.A.; Gitzendanner, M.A.; Sytsma, K.J.; Qiu, Y.L.; Hilu, K.W.; Davis, C.C.; Sanderson, M.J.; Beaman, R.S.; Olmstead, R.G.; Judd, W.S.; Donoghue, M.J.; Soltis, P.S. Angiosperm phylogeny: 17 genes, 640 taxa. Am. J. Bot., 2011, 98(4), 704-730.
[http://dx.doi.org/10.3732/ajb.1000404] [PMID: 21613169]
[7]
Albers, F.; Meve, U. Asclepiadaceae.Illustrated handbook of succulent plants: asclepiadaceae; Springer: Switzerland, 2004, pp. 5-274.
[8]
Burkill, H.M. The useful plants of West tropical Africa, 2nd ed; Royal Botanic Gardens: Kew, 1985.
[9]
Dalziel, J.M. The Useful Plants of West Tropical Africa; Crow Agents: London, 1948.
[10]
Oliver-Bever, B. Medicinal Plants in Tropical West Africa; Cambridge University Press: New York, 1986, pp. 82-83.
[http://dx.doi.org/10.1017/CBO9780511753114]
[11]
Aguwa, C.N.; Mittal, G.C. Study of antiulcer activity of aqueous extract of leaves of Pyrenacantha staudtii (family Icacinaceae) using various models of experimental gastric ulcer in rats. Eur. J. Pharmacol., 1981, 74(2-3), 215-219.
[http://dx.doi.org/10.1016/0014-2999(81)90533-1] [PMID: 7327202]
[12]
Aguwa, C.N.; Okunji, C.O. Gastrointestinal studies of Pyrenacantha staudtii leaf extracts. J. Ethnopharmacol., 1986, 15(1), 45-55.
[http://dx.doi.org/10.1016/0378-8741(86)90103-0] [PMID: 3713227]
[13]
Akubue, P.I.; Mittal, G.C.; Aguwa, C.N. Preliminary pharmacological study of some Nigerian medicinal plants. 1. J. Ethnopharmacol., 1983, 8(1), 53-63.
[http://dx.doi.org/10.1016/0378-8741(83)90089-2] [PMID: 6632937]
[14]
Falodun, A.; Chaudhry, A.; Choudhary, I. Phytotoxic and chemical investigations of a Nigerian medicinal plant. Res. J. Phytochem., 2009, 1, 13-17.
[http://dx.doi.org/10.3923/rjphyto.2009.13.17]
[15]
Falodun, A.A.; Usifoh, C.O. Isolation and characterization of 3-carbomethoxypyridine from the leaves of Pyrenacantha staudtii Hutch and Dalz (Icacinaceae). Acta Pol. Pharm., 2006, 63(3), 235-236.
[PMID: 20085230]
[16]
Falodun, A.; Usifoh, C.O.; Nworgu, Z.A.M. Phytochemical and active column fractions of Pyrenacantha staudtii leaf extracts on isolated rat uterus. Pak. J. Pharm. Sci., 2005, 18(4), 31-35.
[PMID: 16380355]
[17]
Gill, L. Ethnomedical uses of plants in Nigeria; Uniben Press: Benin, 1992, pp. 134-138.
[18]
Hutchinson, J.; Daliziel, J. Flora of West Tropical Africa, 2nd ed; Royal Botanic Gardens: Kew, 1954, pp. 296-828.
[19]
Iwu, M.M. Handbook of African medicinal plants, 2nd ed; CRC press: N.Y., 2014.
[http://dx.doi.org/10.1201/b16292]
[20]
Mesia, G.K.; Tona, G.L.; Penge, O.; Lusakibanza, M.; Nanga, T.M.; Cimanga, R.K.; Apers, S.; Van Miert, S.; Totte, J.; Pieters, L.; Vlietinck, A.J. Antimalarial activities and toxicities of three plants used as traditional remedies for malaria in the Democratic Republic of Congo: Croton mubango, Nauclea pobeguinii and Pyrenacantha staudtii. Ann. Trop. Med. Parasitol., 2005, 99(4), 345-357.
[http://dx.doi.org/10.1179/136485905X36325] [PMID: 15949182]
[21]
Nworgu, Z.A.M.; Falodun, A.; Usifoh, C.O. Inhibitory Effect of 3-Carbomethoxypyridine and 3-Carbobutoxypyridine On Isolated Rat Uterus. Acta Pol. Pharm., 2006, 2, 179-182.
[22]
Falodun, A.; Usifoh, C.O.; Nworgu, Z.A.M. Smooth muscle relaxant activity of 3-carbomethoxylpyridine from Pyrenacantha staudtii leaf on isolated rat uterus. Afr. J. Biotechnol., 2006, 12, 1271-1273.
[23]
Engel, N.; Oppermann, C.; Falodun, A.; Kragl, U. Proliferative effects of five traditional Nigerian medicinal plant extracts on human breast and bone cancer cell lines. J. Ethnopharmacol., 2011, 137(2), 1003-1010.
[http://dx.doi.org/10.1016/j.jep.2011.07.023] [PMID: 21782919]
[24]
Engel, N.; Falodun, A.; Kühn, J.; Kragl, U.; Langer, P.; Nebe, B. Pro-apoptotic and anti-adhesive effects of four African plant extracts on the breast cancer cell line MCF-7. BMC Complement. Altern. Med., 2014, 14, 334.
[http://dx.doi.org/10.1186/1472-6882-14-334] [PMID: 25199565]
[25]
Lawal, B.; Shittu, O.K.; Kabiru, A.Y.; Jigam, A.A.; Umar, M.B.; Berinyuy, E.B.; Alozieuwa, B.U.; Umar, M.B.; Alozieuwa, B.U. Potential antimalarials from African natural products: A reviw. J. Intercult. Ethnopharmacol., 2015, 4(4), 318-343.
[http://dx.doi.org/10.5455/jice.20150928102856] [PMID: 26649238]
[26]
Olorunniyi, O.; Morenikeji, O. In vivo antimalarial activity of crude aqueous leaf extract of Pyrenacantha staudtii against Plasmodium berghei (NK65) in infected mice. Afr. J. Pharm. Pharmacol., 2014, 12, 342-345.
[http://dx.doi.org/10.5897/AJPP2013.3950]
[27]
Awe, E.O.; Makinde, J.M.; Wakeel, O.K.; Adeloye, A.O. Evaluation of analgesic, anticonvulsant and hypnotic activities of Pyrenacanthia staundtii. Afr. J. Trad. CAM., 2005, 2, 122-128.
[http://dx.doi.org/10.4314/ajtcam.v2i2.31110]
[28]
Awe, E.O.; Kolawole, S.O.; Wakeel, K.O.; Abiodun, O.O. Antidiarrheal activity of Pyrenacantha staudtii Engl. (Icacinaceae) aqueous leaf extract in rodents. J. Ethnopharmacol., 2011, 137(1), 148-153.
[http://dx.doi.org/10.1016/j.jep.2011.04.068] [PMID: 21571058]
[29]
Oladoye, S.O.; Fakunle, C.O.; Adeoye, O.A.; Fashola, G.O. Isolation and characterization of an anticonvulsant principle from leaf extract of Pyrenacantha staudtii. J. Nat. Sci. Res., 2013, 13, 69-73.
[30]
Falodun, A.; Siraj, R.; Choudhary, M.I. GC-MS analysis of insecticidal leaf essential oil of Pyrenacantha staudtii Hutch and Dalz (Icacinaceae). Trop. J. Pharm. Res., 2009, 2, 139-143.
[http://dx.doi.org/10.4314/tjpr.v8i2.44522]
[31]
Lorke, D. A new approach to practical acute toxicity testing. Arch. Toxicol., 1983, 54(4), 275-287.
[http://dx.doi.org/10.1007/BF01234480] [PMID: 6667118]
[32]
Ajayi, A.A.; Ukponmwan, O.E. Possible evidence of angiotensin II and endogenous opioid modulation of novelty-induced rearing in the rat. Afr. J. Med. Med. Sci., 1994, 23(3), 287-290.
[PMID: 7604756]
[33]
Leite, J.R.; Carlini, E.A.; Lander, N.; Mechoulam, R. Anticonvulsant effects of the (-) and (+)isomers of cannabidiol and their dimethylheptyl homologs. Pharmacology, 1982, 24(3), 141-146.
[http://dx.doi.org/10.1159/000137588] [PMID: 7071126]
[34]
Rakhshandah, H.; Shakeri, M.T.; Ghasemzadeh, M.R. Comparative hypnotic effect of Rosa damascenes fractions and diazepam in mice. Iran. J. Pharm. Res., 2007, •••, 193-197.
[35]
Rakhshandah, H.; Shakeri, M.T.; Ghasemzadeh, M.R. Comparative hypnotic effect of Rosa damascena fractions and Diazepam in Mice. Iran. J. Pharm. Res., 2010, 6, 193-197.
[36]
Vohora, S.B. Unani Joshandah drugs for common cold, catarrh, cough and associated fevers. J. Ethnopharmacol., 1986, 16(2-3), 201-211.
[http://dx.doi.org/10.1016/0378-8741(86)90090-5] [PMID: 3747564]
[37]
Elisha, E.E.; Maliki, S.J.; Abraham, B.K. Effect of Jasmium officinale flower on the central nervous system of mouse. Int. J. Crude Drug Res., 1988, 26, 221-227.
[http://dx.doi.org/10.3109/13880208809053923]
[38]
Dilnawaz, P.; Shiriskumar, A. Investigation of anticonvulsant activity of Vanda rusburghii. J. Pharmacog. Phytochem., 2014, 2, 95-99.
[39]
Du, X.M.; Sun, N.Y.; Takizawa, N.; Guo, Y.T.; Shoyama, Y. Sedative and anticonvulsant activities of goodyerin, a flavonol glycoside from Goodyera schlechtendaliana. Phytother. Res., 2002, 16(3), 261-263.
[http://dx.doi.org/10.1002/ptr.862] [PMID: 12164273]
[40]
Alice, A.L.; Alvin, J.B. Glycine potentiates strychinine-induced convulsions: role of NMDA receptors. J. Neurosci., 1988, 8(10), 3823-3826.
[41]
Curtis, D.R.; Game, C.J.A.; Lodge, D. Benzodiazepines and central glycine receptors. Br. J. Pharmacol., 1976, 56(3), 307-311.
[http://dx.doi.org/10.1111/j.1476-5381.1976.tb07643.x] [PMID: 1260175]
[42]
Fujimori, H. Potentiation of barbital hypnosis as an evaluation method for CNS depressant. Psychopharmacology (Berl.), 1999, 7, 374-377.
[http://dx.doi.org/10.1007/BF00403761]
[43]
File, S.E.; Pellow, S. Intrinsic actions of the benzodiazepine receptor antagonist Ro 15-1788. Psychopharmacology (Berl.), 1986, 88(1), 1-11.
[http://dx.doi.org/10.1007/BF00310505] [PMID: 3003778]
[44]
Nogueira, E.; Vassilieff, V.S. Hypnotic, anticonvulsant and muscle relaxant effects of Rubus brasiliensis. Involvement of GABA(A)-system. J. Ethnopharmacol., 2000, 70(3), 275-280.
[http://dx.doi.org/10.1016/S0378-8741(99)00205-6] [PMID: 10837989]
[45]
Curtis, D.R.; Duggan, A.W.; Felix, D.; Johnston, G.A.R.; McLennan, H. Antagonism between bicuculline and GABA in the cat brain. Brain Res., 1971, 33(1), 57-73.
[http://dx.doi.org/10.1016/0006-8993(71)90305-2] [PMID: 4330214]
[46]
Kaminski, R.M.; Witkin, J.M.; Shippenberg, T.S. Pharmacological and genetic manipulation of kappa opioid receptors: Effects on cocaine- and pentylenetetrazol-induced convulsions and seizure kindling. Neuropharmacology, 2007, 52(3), 895-903.
[http://dx.doi.org/10.1016/j.neuropharm.2006.10.007] [PMID: 17126860]
[47]
Rogawski, M.A. Diverse mechanisms of antiepileptic drugs in the development pipeline. Epilepsy Res., 2006, 69(3), 273-294.
[http://dx.doi.org/10.1016/j.eplepsyres.2006.02.004] [PMID: 16621450]
[48]
Prut, L.; Belzung, C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: A review. Eur. J. Pharmacol., 2003, 463(1-3), 3-33.
[http://dx.doi.org/10.1016/S0014-2999(03)01272-X] [PMID: 12600700]
[49]
Blanchard, D.C.; Griebel, G.; Blanchard, R.J. Mouse defensive behaviors: Pharmacological and behavioral assays for anxiety and panic. Neurosci. Biobehav. Rev., 2001, 25(3), 205-218.
[http://dx.doi.org/10.1016/S0149-7634(01)00009-4] [PMID: 11378177]
[50]
Vogel, H.G.; Vogel, W.H.W.H. Potentiation of Hexobarbital Sleeping Time.Drug Discovery and Evaluation; Vogel, H.G.; Vogel, W.H., Eds.; Springer-Verlag Berlin Heidelberg: New York, 1997, pp. 267-268.
[http://dx.doi.org/10.1007/978-3-662-03333-3]
[51]
Fujimori, H. Potentiation of barbital hypnosis as an evaluation method for central nervous system depressants. Psychopharmacology (Berl.), 1965, 7(5), 374-378.
[http://dx.doi.org/10.1007/BF00403761] [PMID: 5837313]
[52]
Lu, M-C. Studies on the sedative effect of Cistanche deserticola. J. Ethnopharmacol., 1998, 59(3), 161-165.
[http://dx.doi.org/10.1016/S0378-8741(97)00108-6] [PMID: 9507899]
[53]
Datta, S. Cellular and chemical neuroscience of mammalian sleep. Sleep Med., 2010, 11(5), 431-440.
[http://dx.doi.org/10.1016/j.sleep.2010.02.002] [PMID: 20359944]
[54]
Gottesmann, C. GABA mechanisms and sleep. Neuroscience, 2002, 111(2), 231-239.
[http://dx.doi.org/10.1016/S0306-4522(02)00034-9] [PMID: 11983310]
[55]
Chu, Q.P.; Wang, L.E.; Cui, X.Y.; Fu, H.Z.; Lin, Z.B.; Lin, S.Q.; Zhang, Y.H. Extract of Ganoderma lucidum potentiates pentobarbital-induced sleep via a GABAergic mechanism. Pharmacol. Biochem. Behav., 2007, 86(4), 693-698.
[http://dx.doi.org/10.1016/j.pbb.2007.02.015] [PMID: 17383716]
[56]
Jiang, J.G.; Huang, X.J.; Chen, J.; Lin, Q.S. Comparison of the sedative and hypnotic effects of flavonoids, saponins, and polysaccharides extracted from Semen Ziziphus jujube. Nat. Prod. Res., 2007, 21(4), 310-320.
[http://dx.doi.org/10.1080/14786410701192827] [PMID: 17479419]
[57]
Linck, V.M.; da Silva, A.L.; Figueiró, M.; Piato, A.L.; Herrmann, A.P.; Dupont Birck, F.; Caramão, E.B.; Nunes, D.S.; Moreno, P.R.H.; Elisabetsky, E. Inhaled linalool-induced sedation in mice. Phytomedicine, 2009, 16(4), 303-307.
[http://dx.doi.org/10.1016/j.phymed.2008.08.001] [PMID: 18824339]
[58]
Dehar, N.; Walia, R.; Ratol, S. Potentiation of thiopentone sodium induced hypnosis by Berberis aristata in rodents. Asian J. Pharm. Clin. Res., 2012, 5, 131-133.
[59]
Nyeem, M.A.B.; Alam, M.A.; Awal, M.A.; Mostafa, M.; Uddin, S.J.; Islam, N.; Rouf, R. CNS depressant effect of the crude ethanolic extract of the flowering tops of Rosa damascene. Iranian J. Pharmacol. Therapeut., 2006, 5, 171-174.
[60]
Ayoka, A.O.; Akomolafe, R.O.; Iwalewa, E.O.; Akanmu, M.A.; Ukponmwan, E.O. Sedative, antiepileptic and antipsychotic effect of Spondial monbin in mice and rats. J. Ethnopharmacol., 2006, 103, 166-175.
[http://dx.doi.org/10.1016/j.jep.2005.07.019] [PMID: 16188408]
[61]
Huang, P.; Xiao, A.; Zhou, M.; Zhu, Z.; Lin, S.; Zhang, B. Heritable gene targeting in zebrafish using customized TALENs. Nat. Biotechnol., 2011, 29(8), 699-700.
[http://dx.doi.org/10.1038/nbt.1939] [PMID: 21822242]
[62]
Nicoll, R.A. Introduction to Pharmacology of CNS Drugs.Basic and Clinical Pharmacology, 8th ed; Katzung, B.G., Ed.; Lange Medical Books/McGraw-Hill: New York, USA, 2001, pp. 351-363.
[63]
Gale, K. Subcortical structures and pathways involved in convulsive seizures generation. J. Clin. Neurophysiol. Off. Publ. Am. Electroencephalogr. Soc., 1992, 2, 264-277.
[http://dx.doi.org/10.1097/00004691-199204010-00007]
[64]
Ahmadiani, A.; Mandgary, A.; Sayyah, M. Anticonvulsant effect of flutamide on seizures induced by pentylenetetrazole: Involvement of benzodiazepine receptors. Epilepsia, 2003, 44(5), 629-635.
[http://dx.doi.org/10.1046/j.1528-1157.2003.36402.x] [PMID: 12752460]
[65]
Smith, M.; Wilcox, K.S.; White, H.S. Discovery of antiepileptic drugs. Neurotherapeutics, 2007, 4(1), 12-17.
[http://dx.doi.org/10.1016/j.nurt.2006.11.009] [PMID: 17199014]
[66]
Rang, H.P.; Dale, M.M.; Ritter, J.M. Pharmacology, 4th ed; Churchill Livingstone: USA, 2000, pp. 604-613.
[67]
Adeyemi, O.O.; Yemitan, O.K.; Adebiyi, O.O. Sedative and anticonvulsant activities of the aqueous root extract of Sanseviera liberica Gerome & Labroy (Agavaceae). J. Ethnopharmacol., 2007, 113(1), 111-114.
[http://dx.doi.org/10.1016/j.jep.2007.05.007] [PMID: 17583456]
[68]
Costa, E.; Guidotti, A.; Mao, C.C. Evidence for involvement of GABA in the action of Benzodiazepines: Studies on rat cerebellum.Mechanisms of Action of Benzodiazepines; Costa, E.; Greengard, P., Eds.; Raven Press: UK, 1975, Vol. 14, pp. 113-151.
[69]
Wood, J.D.; Peesker, S.J. The role of GABA metabolism in the convulsant and anticonvulsant actions of aminooxyacetic acid. J. Neurochem., 1973, 20(2), 379-387.
[http://dx.doi.org/10.1111/j.1471-4159.1973.tb12137.x] [PMID: 4698285]
[70]
Marcus, R.; Coulsto, A.M. Water Soluble Vitamins., 1985.
[71]
Hong, J.S. Hippocampal opioid peptides and seizures. Epilepsy Res. Suppl., 1992, 7, 187-195.
[PMID: 1361330]
[72]
Foote, F.; Gale, K. Proconvulsant effect of morphine on seizures induced by pentylenetetrazol in the rat. Eur. J. Pharmacol., 1984, 105(1-2), 179-184.
[http://dx.doi.org/10.1016/0014-2999(84)90665-4] [PMID: 6489446]
[73]
Simmons, M.L.; Chavkin, C. Endogenous opioid regulation of hippocampal function. Int. Rev. Neurobiol., 1996, 39, 145-196.
[http://dx.doi.org/10.1016/S0074-7742(08)60666-2] [PMID: 8894847]
[74]
Lauretti, G.R.; Ahmad, I.; Pleuvry, B.J. The activity of opioid analgesics in seizure models utilizing N-methyl-DL-aspartic acid, kainic acid, bicuculline and pentylenetetrazole. Neuropharmacology, 1994, 33(2), 155-160.
[http://dx.doi.org/10.1016/0028-3908(94)90002-7] [PMID: 7913538]

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