Effect of hyaluronic acid on prevention of adhesion in rats

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(1)³¤¥Èó. * .* a. (2004) 44 4 Korean J Vet Res(2004) 44(4) : 663~668. Ñö*IZBMVSPOJDBDJEö~RFOOæÎöR\. «îÁ«ÁJ'Á;'ÁÖ^¾Á;J^ÁBÎ% ÁB\+Áã7Á;«

(2). *&L >~ *Â& Vjÿ>¶ö (²Òß: 2004j 9ú 15¢) 1. Effect of hyaluronic acid on prevention of adhesion in rats Jong hoon Lee, Joo Myoung Lee, Young min Yun, Tae young Kang, Ho choon Woo, Yoon ho Kang, Nam joong Kim1, Hee seok Kim, Kyoung kap Lee and Jongtae Cheong* Department of Veterinary Medicine, Cheju National University, Cheju 690-756, Korea Department of Companion Animal Science, HyeChon College, Daejeon 302-715, Korea (Accepted= September 15, 2004). 1. Abstracts : This study was conducted to investigate the effect of hyaluronic acid (HA) on prevention of abdominal adhesions depending on various concentrations thereof by inducing an abrasion experimentally in the cecum of rats. Each group was consisted of 10 rats, and 40 rats were divided into 4 groups comprising the saline treatment group, HA 0.4% treated group, 0.6% treated group, and 0.8% treated group. And abrasion was caused in the cecum by using dry gauze and thereby, adhesion was induced. On 7 days after the operation, adhesions of each region were evaluated into the range of 0 ~ 4. Significant difference was found in the adhesion score between the control group and each experimental group (P<0.05). Also, HA 0.4% treatment group showed the lowest adhesion score (P<0.05). In the light of the above results, HA 0.4% solution was more effective on prevention of adhesion than HA 0.6% and 0.8% solution. Key words : cecum, adhesion, abrasion, hyaluronic acid(HA). * . >æ pj ãÖ RFj^

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(7) ~ Wj ÛB~º WËº" transforming growth factor-βf ?f · cytokine " &>Ú FOj 6²Êº © [16]. B >F ê ; Ú¦ ËV *~ FO ;Wj O æ~V *~ ôf ªç' & B~² ê¯> ® . 7öB ï~ ~F& ¢Ú¾º ÿnö R F² Rj bÒ'b ªÒB FOj ÛB Ò Ï'b ÒÏ®~ BB .Vöº *î Ï Ò">, Ringer j FO OæB ÒÏ~&. Ò² 5 ÿböB B >F ê z® B~º ^B 6f ;ËV~ FO [2]. ; [1] 5 [4]f ¶§ >F ê ¢Ú¾º >; Ú ËV~ FOf > N &~, FÖ, »¦ê, ï", > ;W Ë 5 V ;j FB > ® ~&, Ellis [13]f ;ËV~ FO Ëöï, ²z Ë, ;ËV 5 VË Ë ÷Ã~ B ¸ ~& . f ? ® &~f ÖW &~ö 'Ëj "º º 7 FO Næ~º j7f Ö ~& [24]. Â& >F ;ËV¢ ·~º >Fj ê 8¢ Æ ;ã ¦Ò¢ ®j r 202« 7 188«öB FOj { > ® ~& [35]. FOf RF² ¦Ob >F ê 3¢ æ¾ê >. *Corresponding author: Jongtae Cheong Department of Veterinary Medicine, Cheju National University, Cheju 690-756, Korea [Tel: +82-64-754-3370, Fax: +82-64-725-3380, E-mail: [email protected]]. 663.

(8) 664. «îÁ"«ÁJ'"Á;'ÁÖ^¾Á;J^ÁBÎ7ÁB\+Áã7Á;«. b¾, BBº ; ÚöB >& Ò ¢Ú¾ ± f Î"¢ áæ á~& [6, 25]. $ Dextran, zz Êr, "Ã BB j 'Ï~º þ ®îº [5, 18, 26] BB f öÒN~ Ã&, Â., VË~ ÛB 5 Ú76² ~ &æ ¦·Ïj ¾ æÚî . Moll [24]f sodium carboxymethylcellulose (SCMC) Ï "'b FBB .V FO Oæ [29] 5 ÒF O Oæ¢ * Ï'b ÒÏ~&j r Î"'î. ~&, ; [3]f BöB ; Ú FOj F BÎ ê ¦*¢ ªÒ r, ÒFO Oæ¢ * SCMC¢ ; Úö ÒÏ®j r Î"'î ~& . SCMC~ FO Oæ V*f ; ÚöB ¶çj Af ËV~ Ëï ç7'b 7/~º ©j Oæ~ , J·Ïj b FOj Oæ~º ©b rJ ^ ® [7, 11, 22, 34, 38]. Rodgers [27], Koqak [21], Sawada [30]f hyaluronic acid(HA) Ï "'b FBB .V~ FO Bj ÛBÒ Ï'b ÒÏ~&j r Î"' î ~& . HAº N-acetyl glucosamine" D-glucuronic acid WB polysaccharide Ú'W Ö>~, ZëW . HA~ Òz' ßWf J·Ï, Ú~ ç W Fæ, .Ë Wî~ ª

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(12) Ãj ÛBÊ .²6 w VËj 6²Úb FOj .O [33]. Urman [37]f v~ ¶§'j .& ç¾ÚV *ö HA 0.25%, HA 0.4%, PBS¢ ; Úö R~ 14¢ ê ö {j ®j r HA 0.4%¢ ÒÏ R &Ë FO .Oö Î"'î ~& [36]. Seeger [32]f o# >F ê o#j V *ö SCMC 0.1% f HA 0.4%¢ IÚ" 6" êö {j ®j r ~ FO ;W 'îb¾ HA 0.4%¢ ÒÏ öB FOB Ô~ ~& . Holzman [19]f Æ¢öB Ë^ >F ê phosphate-buffered saline(PBS) f HA 0.4%, HA 1% Ïj ;j V *ö "« ê 2"¢ êö Bj ®j r PBSº *Ú 7öB 70% ;ê& FO B~& HA 0.4%öBº 10% ;ê& FO B~&b, HA 1%öBº 30% ;ê FO B ~& . V¢B þf HA 0.4 ~ 1% ÒöBº ;{ F. O ãËj r > ìÚ HA~ ³ê¢ 0.4%, 0.6% 5 0.8% ;~ FO;ê¢ jv~¶ ~& .. Òò 5 O». þ ÿ> £ 8 "_ B 300 g Ú~ z Sprague-Dawley rat ¢ þö ÒÏ~& . HA 0.4%, HA 0.6% 5 HA 0.8% R" saline Rj ' 10îÒO V~~& . ÏW Hyaluronic acid(LG Life Science Ltd, MW: 1,100 kDa) º Ã~>ö 0.4%, 0.6% 5 0.8% Ïb ò. r, membrane filter(0.25 µm) ¾Ò~& . FO FB O» Ketamine HCl(Ketalar , F·¯, 60 mg/kg)" xylazine HCl(Rompun , :þz, 7 mg/kg)b "G"Ò ~ î¢ ~& . ÿbj f* ;~, ~¦ ¢ ;7 .B~ B ê ; Ú ËV¢ ·~V *ö ' ê ¾~Ï 2 mlj ;ö "«~&, V "ç FB ¦* Ëö '' 1 ml~ Ïj V"ç FB *ö ê

(13) ~& . ¦*ö î ®¢ Ï~ '' 1 cm V Ëï Â. F rræ V"çj F BÎ r ;j V *ö 1 ml~ Ïj "«~&. . ã" b~º 4-0 polyglycolic acid (Dexon , Sherwood-Davis & Geck, USA)j Ï~ B³/ j ~&, b¦º 4-0 nylonb BÖ. /~&. . >F *, ê Bº R~æ p~ . FO~ ï& >F 7¢ ê, Î þÿb j ãº îÎ ê ¦ ¦j ~ FO B ¦¢ {~& . þ' > F .Nf ¢; ö &~ ræ á~º ^ Ò²~ > ~Ò¢ 6;&b ~, Table 1" ? ; [3]~ O »b FO ;ê¢ ï&~& . Ûê ¾Ò Ûê ¾Òº ANOVA test¢ Ï~ ' *~ F . . 2. . Table 1. Scoring system for adhesion Grade 0 1 2 3 4. Description of Adhesions No macroscopic adhesions Thin, filmy and easily separated adhesions Thick avascular and limited to one side Thin vascular and limited to one side Thick vascular and limited more than two sides.

(14) Ñö* hyaluronic acidö ~R FO Oæ Îö R \. ~Wj ¦Ã~& .. Table 4. Comparison of postoperative adhesion sites. Ö . Group Sites. V"ç FB ¦* ËöB FO ;êº saline R öB 3.53Û0.36, HA 0.4% RöB 1.10Û0.45, HA 0.6% RöB 2.67Û0.54 Ò HA 0.8% R öB 3.17Û0.39~ adhesion score¢ ¾æÚî . Saline R" HA 0.4%, HA 0.6% 5 HA 0.8% Rj ' ' jv®j r saline Rö j HA 0.4%, HA 0.6% 5 HA 0.8% RöB FOB Ô~ . 7ö B HA 0.4% RöB FOB &Ë Ô~b (P<0.001), HA 0.6% R(P<0.005), HA 0.8% R (P<0.04) Bb FOB Ô~ . HA R *~ jvöBº ' *ö Îv F~W ®º N¢ & (P<0.05), HA 0.4% RöB FO B &Ë Ô~. (Table 2). Î þÿböB V"ç FB¦*f V"ç jF B¦*¢ « FO ;Wf HA 0.4%, HA 0.6%, HA 0.8% RöB '' 27.5%, 65%, 80% ¾æ Ò saline RöBº 87.5% &Ë ¸² ¾æÒ. (Table 3). Ë ËVfê B FO >îº, saline RöBº Ë" ²Ë, ã, çË, ïöB FO B~&, HA 0.4% RöBº Ë, ²Ë" ãöB FO B~& . HA 0.6% RöBº Ë" ²Ë, ã, ÖËöB FO ¢ÚÒ, HA 0.8% RöBº Ë" ²Ë, ã, çË, ïöB FO ¢ÚÒ (Table 4). Table 2. Comparison of adhesion scores after hyaluronic acid (HA) treatment Group. 665. Adhesion score. Û0.36 Û0.45 Û0.54 Û0.39. Saline HA 0.4% HA 0.6% HA 0.8%. 3.53 1.10 2.67 3.17. b c d. P-valuea P<0.001 P<0.005 P<0.04. a. ; Compared with saline group ; The value with different superscripts in the column is significantly different in adhesion scores (P<0.05). b,c,d. Table 3. Percentage of adhesion formation Saline. HA 0.4%. HA 0.6%. HA 0.8%. 87.5. 27.5. 65. 80. No adhesion C+C C+S C+P S+P Co+G C+S+P+G C+S+P+G+Co Numbers(n). Saline 0.4% HA 0.6% HA 0.8% HA − 2 2 1 2 1 1 1 10. 6 1 2 1 − − − − 10. − 2 1 1 3 2 1 − 10. − 2 2 2 1 2 − 1 10. *C: Cecum, Co: Colon, G: Greater omentum, P: Peritoneum, S: Small intestine. V. FOf ç~ ç¾ 6", bî b ~ Ú& "Ã>wj ¢bB RF²ö~ âÂ, RFj^

(15) ~ Ãb ~ fibrin matrix& çzçö Vî z& >Ú B~² B [24]. Goldberg [17]f Â. ÿ>B ¶çöB FO B ~& . . þöBê ¶ç ¦*ö Â. ^ rræ V"çj FBÎ Ö" ' öB · ·ç~ FO B~ & . HA Ïf >F · *ö çö "«~º © F O ;W .Oö z Î"' [10]. FO .O BB. f öBW ö >º "ê >F ·b B> º cçb¦V çj ^ [12]. HA Ïf j¦OW, J·Ï" ç ^ ·Ï ® . Kaufman [20]f >F Òòf ç *~ 7/b ;W>º FOf >W~ 7Ú Ïj >F · *ö "«~ ÛBÒ > ® ~& . ¢ " þöB rat¢ &çb þ Ö" HA 0.4% R (1.10Û0.45)öB FO 6>& &Ë Ô~, saline R(3.53Û0.36)öB FO 6>& &Ë ¸~ . HA 0.4%, HA 0.6% 5 HA 0.8% Rj '' jv®j r FO 6>º Îv F~W ®îb HA 0.4%, HA 0.6% 5 HA 0.8% RöBº HA 0.4% R & Ë Ôf FO;Wj ¾æÚî (P<0.001). Ò saline RöB FO B~ nê& ¸~º Fº saline 24* nö ;öB ² >>Ú >; Ú ËV j ªÒÊ JÊº VË ² ² >V r^ ©b º;B [6]. Î þÿböB V"ç FB¦* 5 V"ç jFB¦*~ FO ;Wj WªN ¾æÚîj r HA 0.4% RöB 27.5% Ô² ¾æÒ saline RöBº 87.5% ¸² ¾æ.

(16) 666. «îÁ"«ÁJ'"Á;'ÁÖ^¾Á;J^ÁBÎ7ÁB\+Áã7Á;«. Ò . ©b >; 5 ; >FöB >F"; 7 &æ º ~ >F ¦* ~ ¦*öB ê · FO ;WF > ®rj r > ®î . Ë " FOB ¦*º Ë, ²Ë, ï, ÖË, ï &V >î . Ë" V"ç FB ¦*& FO ¾ Úê Fº ¦'b Ë~ V(çã : 10 mm) & B "* ËVf~ 7/ n®® ¢ÚÒV r ^¢ ÒòB . Seeger [32]f B~ Óö V"ç j «& FOj FB ê Ringer's Ïj &b HA 0.1%, HA 0.4% Ïj 'Ï Ö" HA 0.4% Ï HA 0.1% ±f FO .O Î"¢ & ~& . Burns [8]f BöB ; >F ê saline, phosphate-buffered saline(PBS), HA 0.1%, HA 0.25% 5 HA 0.4% Ïj ³êê ;j V *ö "« ê ¢"¢ êö FO ;ê¢ rj~j r HA 0.4% Ï FO .Oö &Ë Î"'î ~& . Holzman [19]f New Zealand White rabbits¢ ; >F ê HA 0.4% Ï, HA 1% Ï 5 PBS¢ ;j V *ö "« ê 14¢ ö FO ;ê¢ rj~ j r HA 0.4% Ïj ÒÏ öBº £ 10%ò FO ¢ÚÒ HA 1% ÏöBº 30%& FO ¢ ÚÒ ~& . $ PBS¢ ÒÏ öBº 70% ; ê& FO ¢Ú¾ FO .Oj *Bº HA 0.4% Ï j ÒÏ~º © z Î"'î ~& . . þöB jv ~j r HA 0.4% Ï &Ë Ö>~ HA 0.4% Ï ³ê& ¸¾ Ôj r FO . O Î"& ÎÚrº Fº HA Ï ³êf ª ¶ï .Z î> HA Ïf 6ê& >Ú B oöB J·Ïj ~æ á~V r^ö FO .Oö Î "'æ á~, ³ê& .Z Ôjæ HA Ï J ·Ï" .²6 wÛB VË ÎÚ^ FO .Oö Î"'æ á ©¢ ÒòB . ©f FO .O" HA~ 6êW &ê& ® º [8]f HA¢ ª¶ ¢ ÒÏ®j r &6êf &ª¶ ÒÏ®j r z Î"'î [27, 28]º öBê r > ® . þöB ; >F saline R" HA 0.4%, HA 0.6% 5 HA 0.8% Rj jv®j r HA 0.4% Ï FO ;W .Oö &Ë Î"' Ö"¢ ¾æÚ î .. Ö . ÑöB þ'b Ëö V"çj FBÎ ê Rj &b HA 0.4%, HA 0.6%, HA Rb J;~ ³êê HA Ï~ FO . O Î"¢ ï&~& . V"ç FB ¦*~ adhesion. saline 0.8%. º Ò">¢ R 3.53Û0.36, HA 0.4% R 1.10Û0.45, HA 0.6% R 2.67Û0.54, Ò HA 0.8% R 3.17Û0.39 ¾æÒ . & 5 ' þ *öº FO 6>& Îv F~ W ®º N¢ ¾æÚî(P<0.05), þ *öº HA 0.4% R &Ë FO B Ô~ (P<0.05). ç~ Ö" Ú " r ÑöB B >F~ Ö" FBB ; Ú FOöº HA 0.4% Ï HA 0.6%, HA 0.8% Ï FO .Oö z Î"'¢ .çB .. score. ^^ò. ;, RÆ, Î«. vö* cçö ~ F O;9ö & . ªç>~²æ. 1992, 9, 219-235. Î«, RÆ, ;, ;Ï. Sodium 2. Carboxymethylcellose 5 Dextran 70j Ï FO ;9 Oæö & . II. FO¶ ê Sodium Carboxymethylcellose 5 Dextran 70~ 4& Æ¢ ~ .çö ~º 'Ë. ªç>~²æ. 1993, 10, 227-235. ;« ;« , ã7, Ë%^. Bö* ;FO Sodium 3. Carboxymethylcellose¢ Ï ÒFO~ .O. ªç>~²æ 161-167. RÆ, Î«, .B1996,. 5. 14, vö* Carboxymethylcellose 4. 5 Ibuprofenj Ï FO;9 Oæö & . ªç>~²æ. 1993, 10, 203-214.. 1.. 5. Adhesion Study Group. Reduction of postoperative pelvic adhesions with intraperitoneal 32% Dextran 70: a prospective, randomized clinical trial. Fertil. Steril. 1983, 40, 612-619. 6. Bhatia, D. S. and Allen, J. E. The prevention of experimentally induced postoperative adhesions. Am. Surg. 1997, 63, 775-777. 7. Burns, J. W., Burgess, L., Skinner, K., Rose, R., Jude, C. M. and Diamond, M. P. A hyaluronate based gel for the prevention of postsurgical adhesions: evaluation in two animal species. Fertil. Steril. 1996, 66, 814-821. 8. Burns, J. W., Skinner, K., Colt, J., Sheidlin, A., Bronson, R., Yaccobi, Y. and Goldberg, E. P. Prevention of tissue injury and postsurgical adhesion by precoating tissues with hyaluronic acid solutions. J. Surg. Res. 1995, 59, 644-652. 9. diZerega, G. S. Contemporary adhesion prevention. Fertil. Steril. 1994, 61, 223-228. 10. Duncan, D. A., Carmichael, M. J., Goldberg, E. P., Mines, M. and Yaacobi, Y. Prevention of postoperative.

(17) Ñö* hyaluronic acidö ~R FO Oæ Îö R \ 11.. 12.. 13.. 14.. 15.. 16.. 17.. 18. 19.. 20.. 21.. 22.. pericardial adhesions with hydrophilic polymer solution. J. Surg. Res. 1988, 45, 44-49. Elkins, T. E., Ahokas, R. A., Bury, R. J., Homsey, C. A., Ling, F. W., Malinak, L. R. and Ritter, J. L. Adhesion prevention by solutions of sodium carboxymethylcellulose in the rat. Fertil. Steril. 1984, 41, 926928. Ellis, H. The cause and prevention of prevention of postoperative intraperitoneal adhesions. Surg. Gynecol. Obstet. 1971, 133, 497-511. Ellis, H., Buchan, S., Crowe, A., Hawthom, R., Lower, A., McGuire, A., Menzies, D., Moran, B., O'Brien, F., Parker, M., Thompson, J., Wilson, M. and Lower, A. Adhesion-related hospital readmissions after abdominal and pelvic surgery. Lancet. 1999, 353, 1476. Fraser, J. R. E. and Laurent, T. C. Turnover and metabolism of hyaluronan. In: The Biology of Hyaluronan. pp. 41-53, Chichester, London, 1989. Fraser, J. R. E., Laurent, T. C. and Laurent, U. B. G. Hyaluronan: its nature, distribution, functions, and turnover. J. Intern. Med. 1997, 242, 27-33. Fukazawa, M., Rodgers, K. E. and Yanagihara, D. L. The mitogenic activity of peritoneal tissue repair cells: control by growth factors. J. Surg. Res. 1989, 47, 45-51. Goldberg, E. P., Habal, M. B. and Sheets, J. W. Peritoneal adhesions: prevention with the use of hydrophilic polymer coatings. Arch. Surg. 1980, 115, 776-780. Holtz, G. Current use of ancillary modalities for adhesion prevention. Fertil. Steril. 1985, 44, 174-176. Holzman, S., Connolly, R. J. and Schwaitzberg, S. D. Effect of hyaluronic acid solution on healing of bowel anastomoses. J. Invest. Surg. 1994, 7, 431-437. Kaufman, H. E., Katz, J., Valenti, J., Sheets, J. W. and Goldberg, E. P. Corneal endothelium damage with intraocular lenses: contact adhesion between surgical materials and tissue. Science. 1977, 198, 525-527. Koqak, I., Unlu, C., Akcan, Y. and Yakin, K. Reduction of adhesion formation with cross-linked hyaluronic acid after peritoneal surgery in rats. Fertil. Steril. 1999, 72, 873-878. Leach, R. E., Burns, J. W., Dawe, E. J., SmithBarbour, M. D. and Diamond, M. P. Reduction of postsurgical adhesion formation in the uterine horn model with use of hyaluronate/carboxymethylcellulose. 667. gel. Fertil. Steril. 1998, 69, 415-418. 23. Mast, B. A., Diegelmann, R. F., Krummel, T. M. and Cohen, I. K. Hyaluronic acid modulates proliferation, collagen and protein synthesis of cultured fetal fibroblasts. Matrix. 1993, 13, 441-446. 24. Moll, H. D., Schumacher, J., Wright, J. C. and Spano, J. S. Evaluation of sodium carboxymethylcellulose for prevention of experimentally induced abdominal adhesions in ponies. Am. J. Vet. Res. 1991, 52, 88-91. 25. Rein, M. S. and Hill, J. A. 32% dextran 70(Hyskon) inhibits lymphocyte and macrophage function in vitro: a potential new mechanism for adhesion prevention. Fertil. Steril. 1989, 52, 88-91. 26. Replogle, R. L., Johnson, R. and Gross, R. E. Prevention of postoperative intestinal adhesions with combined promethazine and dexamethasone therapy: Experimental and clinical studies. Ann. Surg. 1966, 163, 580-588. 27. Rodgers, E., Joseph, C., Johns, B., diZerega, G. S. and Wefki, G. Reduction of adhesion formation with hyaluronic acid after peritoneal surgery in rabbits. Fertil. Steril. 1997, 67, 553-558. 28. Rooney, P., Kumar, S., Ponting, J. and Wang, M. The role of hyaluronan in tumour neovascularization. Int. J. Cancer. 1995, 60, 632-636. 29. Ryan, C. K. and Sax, H. C. Evaluation of a carboxymethylcellulose sponge for prevention of postoperative adhesions. Am. J. Surg. 1995, 169, 154160. 30. Sawada, T., Tsukada, K., Hasegawa, K., Ohashi, Y., Udagawa, Y. and Gomel, V. Cross-linked hyaluronate hydrogel prevents adhesion formation and reformation in mouse uterine horn model. Hum. Reprod. 2001, 16, 353-356. 31. Scott, J. E. Extracellular matrix, supramolecular organisation and shape. J. Anat. 1995, 187, 259-269. 32. Seeger, J. M., Kaelin, L. D., Staples, E. M., Yaacobi, Y., Bailey, J. C., Normann, S., Burns, J. W. and Golberg, E. P. Prevention of postoperative pericardial adhesions using tissue-protective solutions. J. Surg. Res. 1997, 68, 63-66. 33. Shushan, A., Mor-Yosef, S. and Avgar, A. Hyaluronic acid for preventing experimental postoperative intraperitoneal adhesion. J. Reprod. Med. 1994, 39, 398-402. 34. Trent, A. M. and Baily, J. V. Bovine peritoneum: Fibrinolytic activity and adhesion formation. Am. J..

(18) 668. «îÁ"«ÁJ'"Á;'ÁÖ^¾Á;J^ÁBÎ7ÁB\+Áã7Á;«. Vet. Res. 1986, 47, 653-659. 35. Trimbos-Kemper, T. C., Trimbos, J. B. and van Hall, E. V. Adhesion formation after tubal surgery: results of the eighth-day laparoscopy in 188 patints. Fertil. Steril. 1985, 43, 395. 36. Urman, B. and Gomel, V. Effect of hyaluronic acid on postoperative intraperitoneal adhesion formation and reformation in the rat model. Fertil. Steril. 1991, 56, 568-570.. 37. Urman, B., Gomel, V. and Jetha, N. Effect of hyaluronic acid on postoperative intraperitoneal adhesion formation in the rat model. Fertil. Steril. 1991, 56, 563567. 38. Vural, B., Mervan, R., Corakci, A., Ozeren, S., Keskin, N., Vural, S., Yucesoy, I. and Erk, A. A trial of reducing adhesion formation in a uterine horn model. Gynecol. Obstet. Invest. 1998, 45, 58-61..

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