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Healing of colonic anastomosis in rats under obstructive ileus conditions

DISCOVERIES (ISSN 2359-7232), 2021, April-June issue

CITATION: 

Despoudi K, Mantzoros I, Ioannidis O, Loutzidou L, Christidis P, Chatzakis C, Gkasdaris G, Raptis D, Pramateftakis MG, Angelopoulos S, Zaraboukas T, Koliakos G, Tsalis KHealing of colonic anastomosis in rats under obstructive ileus conditions. Discoveries 2021, 9(2): e129. DOI: 10.15190/d.2021.8


Submitted: March 23, 2021; Revised: May 09, 2021; Accepted: May 10, 2021; Published: June 30, 2021; 

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Healing of colonic anastomosis in rats under obstructive ileus conditions

Kalliopi Despoudi (1), Ioannis Mantzoros (1), Orestis Ioannidis (1,*), Lydia Loutzidou (1), Panagiotis Christidis (1), Christos Chatzakis (1), Grigorios Gkasdaris (1), Dimitrios Raptis (1), Manousos George Pramateftakis (1), Stamatios Angelopoulos (1), Thomas Zaraboukas (2), George Koliakos (3), Konstantinos Tsalis (1)

(1) 4th Academic Department of Surgery, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece

(2) Department of Pathology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece

(3) Department of Biochemistry, School of Medicine, Aristotle University of Thessaloniki, Greece


*Corresponding authors: Dr. Orestis Ioannidis, MD, MSC, PhD, 4th Academic Department of Surgery, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Alexandrou Mihailidi 13, 54640 Thessaloniki, Greece; Phone: +302310814161; Fax: +302310551301; Email: telonakos@hotmail.com

Abstract

Background: The anastomosis leak in colon resections is a crucial post-operative complication with significant morbidity and mortality. 

Methods: Forty (40) Wistar rats were allocated in two groups. In SHAM group only anastomosis was performed. In ILEUS group anastomosis was performed following one day of ileus. Animals in both groups were subdivided in two groups according to the day they were sacrificed, 4th or 8th post-operative day. A number of variables between the groups were estimated.

Results: Body weight loss was higher following obstructive ileus on both days. Adhesion score in 4th and 8th post-operative day was higher in ILEUS1, ILEUS2 groups compared to SHAM1, SHAM2 groups respectively (p<0.001 for both). Neovascularization decreased following obstructive ileus compared to control on the 4th day (ILEUS1 vs. SHAM1, p=0.038). Bursting pressure was lower in ILEUS2 group than SHAM2 group (p<0.001). The number of fibroblasts decreased following obstructive ileus compared to control on the 4th and 8th day (ILEUS1 vs. SHAM1, p=0.001, ILEUS2 vs SHAM2, p=0.016). Hydroxyproline concentration was decreased in ILEUS2 group compared to SHAM2 group (p<0.001).

Conclusions: The balance of collagenolysis and collagenogenesis plays a decisive role in the healing of anastomoses following bowel obstruction. Under those circumstances, anastomosis’ bursting pressure is reduced owning to decreased neovascularization, reduced fibroblast presence and lower hydroxyproline concertation. In our study, local inflammation, neocollagen concentration and collagenase activity were not associated with this adverse effect. However, further research should delineate the mechanisms of healing of colonic anastomoses and identify those factors that can improve our outcomes.

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References

1. Pramateftakis MG, Kanellos D, Vrakas G, Tsachalis T, Raptis D, Makrantonakis  a, Koukouritaki Z, Kanellos I. Progress in rectal cancer staging and treatment. Tech Coloproctol 2010;14:29–31.
2. Kanellos I, Vasiliadis K, Angelopoulos S, Tsachalis T, Pramateftakis MG, Mantzoros I, Betsis D. Anastomotic leakage following anterior resection for rectal cancer. Tech Coloproctol 2004;8.
3. Mantzoros I. Oncologic impact of anastomotic leakage after low anterior resection for rectal cancer. Tech. Coloproctol.2010;14.
4. Kanellos D. Anastomotic leakage after colonic resection. Tech Coloproctol 2010;14.
5. Rygl M, Novotna J, Herget J, Skaba R, Snajdauf J. Parameters of healing in approximative intestinal anastomosis. Eur J Pediatr Surg 2009;19:25–9.
6. Witte MB, Barbul A. Repair of full-thickness bowel injury. Crit Care Med 2003;31:S538-46.
7. Gainant A. Prevention of anastomotic dehiscence in colorectal surgery. J Chir (Paris) 2000;137:45–50.
8. Abete M, Ronchetti V, Casano A, Pescio G. Anastomotic leakage after traditional surgery of the colon and rectum. Minerva Chir 2003;58:167–74.
9. Moran BJ, Heald RJ. Anastomotic leakage after colorectal anastomosis. Semin. Surg. Oncol.2000;18:244–8.
10. Walker KG, Bell SW, Rickard MJFX, Mehanna D, Dent OF, Chapuis PH, Bokey EL. Anastomotic leakage is predictive of diminished survival after potentially curative resection for colorectal cancer. Ann Surg 2004;240:255–9.
11. Rolim MF, Riger CJ, Eleutherio ECA, da Fonseca Colao C, Cotta Pereira G, Schanaider A. Colonic healing after portal ischemia and reperfusion: An experimental study with oxidative stress biomarkers. Redox Rep 2007;12:267–74.
12. Roscher R, Lommel K. Pathophysiology of ileus. Zentralbl Chir 1998;123:1328–33.
13. Cuffy M, Abir F, Audisio RA, Longo WE. Colorectal cancer presenting as surgical emergencies. Surg. Oncol.2004;13:149–57.
14. Pavlidis TE. Carcinoma of the colon caused intussusception presenting with obstructive ileus 2. Int. J. Colorectal Dis.2007;22:337.
15. van der Ham AC, Kort WJ, Weijma IM, van den Ingh HFGM, Jeekel H. Effect of antibiotics in fibrin sealant on healing colonic anastomoses in the rat. Br J Surg 1992;79:525–8.
16. Galanopoulos G, Raptis D, Pramateftakis MG, Mantzoros I, Kanellos I, Lazarides C. The effects of iloprost on colonic anastomotic healing in rats under obstructive ileus conditions. J Surg Res 2014;189:22–31.
17. Kanellos D, Pramateftakis MG, Mantzoros I, Zacharakis E, Raptis D, Despoudi K, Zaraboukas T, Koliakos G, Lazaridis H. The effects of the intraperitoneal administration of oxaliplatin and 5-FU on the healing of colonic anastomoses: an experimental study. Tech Coloproctol 2011;15:1–5.
18. Sapidis N, Tziouvaras C, Ioannidis O, Kalaitsidou I, Botsios D. The effect of glutamine and synbiotics on the healing of colonic anastomosis. Rev Esp Enfermedades Dig 2014;106:255–62.
19. Phillips JD, Kim CS, Fonkalsrud EW, Zeng H, Dindar H. Effects of chronic corticosteroids and vitamin a on the healing of intestinal anastomoses. Am J Surg 1992;163:71–7.
20. Shomaf M. Histopathology of human intestinal anastomosis. East Mediterr Heal J 2003;9:413–21.
21. Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem 1996;29:225–9.
22. Hewitt CW, Marra SW, Kann BR, Tran HS, Puc MM, Chrzanowski FA, Tran JL V., Lenz SD, Cilley JH, Simonetti VA, Delrossi AJ. BioGlue surgical adhesive for thoracic aortic repair during coagulopathy: Efficacy and histopathology. Ann Thorac Surg 2001;71:1609–12.
23. Raptis D, Mantzoros I, Pramateftakis MG, Despoudi K, Zaraboukas T, Koliakos G, Kanellos I, Lazarides C. The effects of tacrolimus on colonic anastomotic healing in rats. Int J Colorectal Dis 2012;27:299–308.
24. Suzuki M, Takahashi A, Toki F, Hatori R, Tomomasa T, Morikawa A, Kuwano H. The effects of intestinal ischemia on colonic motility in conscious rats. J Gastroenterol 2008;43:767–73.
25. Kanellos I, Blouhos K, Demetriades H, Pramateftakis MG, Mantzoros I, Zacharakis E, Betsis D. The failed intraperitoneal colon anastomosis after colon resection. Tech Coloproctol 2004;8.
26. Lopez-Kostner F, Hool GR, Lavery IC. Management and causes of acute large-bowel obstruction. Surg Clin North Am 1997;77:1265–90.
27. Stephenson JA, Singh B. Intestinal obstruction. Surg Internet 2011;29:33–8.
28. Dabareiner RM, Sullins KE, White NA, Snyder JR. Serosal injury in the equine jejunum and ascending colon after ischemia-reperfusion or intraluminal distention and decompression. Vet Surg 2001;30:114–25.
29. Lindeström LM, Ekblad E. Structural and neuronal changes in rat ileum after ischemia with reperfusion. Dig Dis Sci 2004;49:1212–22.
30. Zucchetti F, Negro F, Matera D, Bolognini S, Mafucci S. Colorectal cancer: Obstruction is an independent negative prognostic factor after radical resection. Ann Ital Chir 2002;73:421–5.
31. Ripamonti CI, Easson AM, Gerdes H. Management of malignant bowel obstruction. Eur J Cancer 2008;44:1105–15.
32. Villar JM, Martinez AP, Villegas MT, Muffak K, Mansilla A, Garrote D, Ferron JA. Surgical options for malignant left-sided colonic obstruction. Surg Today 2005;35:275–81.
33. Dindo D, Weishaupt D, Lehmann K, Hetzer FH, Clavien PA, Hahnloser D. Clinical and morphologic correlation after stapled transanal rectal resection for obstructed defecation syndrome. Dis Colon Rectum 2008;51:1768–74.
34. Huang T-J, Wang J-Y, Lee L-W, Chen F-M, Chuan C-H, Chan H-M, Hou M-F, Huang C-J, Huang Y-S, Hsieh J-S. Emergency one-stage surgery for obstructing left-sided colorectal carcinomas. Kaohsiung J Med Sci 2002;18:323–8.
35. Eckmann C, Kujath P, Schiedeck THK, Shekarriz H, Bruch H-P. Anastomotic leakage following low anterior resection: results of a standardized diagnostic and therapeutic approach. Int J Colorectal Dis 2004;19:128–33.
36. Kjaergard HK. Suture support: is it advantageous? Am J Surg Internet 2001;182:15S–20S.
37. Carlson MA, Longaker MT. The fibroblast-populated collagen matrix as a model of wound healing: a review of the evidence. Wound Repair Regen Internet 2004;12:134–47.
38. Carlisle CR, Sparks EA, Der loughian C, Guthold M. Strength and failure of fibrin fiber branchpoints. J. Thromb. Haemost.2010;8:1135–8.
39. Tettamanti G, Grimaldi A, Congiu T, Perletti G, Raspanti M, Valvassori R, de Eguileor M. Collagen reorganization in leech wound healing. Biol Cell 2005;97:557–68.
40. Ottani V, Martini D, Franchi M, Ruggeri A, Raspanti M. Hierarchical structures in fibrillar collagens. Micron 2002;33:587–96.
41. Snyder JR. The pathophysiology of intestinal damage: effects of luminal distention and ischemia. Vet Clin North Am Equine Pract 1989;5:247–70.
42. Zanoni FL, Benabou S, Greco KV, Moreno ACR, Cruz JWMC, Filgueira FP, Martinez MB, Figueiredo LFP de, Silva MR e, Sannomiya P. Mesenteric microcirculatory dysfunctions and translocation of indigenous bacteria in a rat model of strangulated small bowel obstruction. Clinics 2009;64.
43. Rolim MF, Riger CJ, Eleutherio EC, Colao Cda F, Pereira GC, Schanaider A. Colonic healing after portal ischemia and reperfusion: an experimental study with oxidative stress biomarkers. Redox Rep Internet 2007;12:267–74.
44. Abela CB, Homer-Vanniasinkham S. Clinical implications of ischaemia-reperfusion injury. Pathophysiol  Off J Int Soc Pathophysiol  2003;9:229–40.
45. Tanaka R, Mochizuki H, Suzuki A, Katsube N, Ishitani R, Mizuno Y, Urabe T. Induction of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression in rat brain after focal ischemia/reperfusion. J Cereb Blood Flow Metab 2002;22:280–8.
46. Madl C, Druml W. Systemic consequences of ileus. Bailliere’s Best Pract Res Clin Gastroenterol 2003;17:445–56.
47. Serpytis M, Ivaskevicius J. Intra-abdominal hypertension and multiple organ dysfunction syndrome. Med  2005;41:903–9.
48. Anderova M, Vorisek I, Pivonkova H, Benesova J, Vargova L, Cicanic M, Chvatal A, Sykova E. Cell death/proliferation and alterations in glial morphology contribute to changes in diffusivity in the rat hippocampus after hypoxia-ischemia. J Cereb Blood Flow Metab 2011;31:894–907.
49. Palys MD, Haffajee AD, Socransky SS, Giannobile W V. Relationship between C-telopeptide pyridinoline cross-links (ICTP) and putative periodontal pathogens in periodontitis. J Clin Periodontol 1998;25:865–71.
50. Trenti L, Biondo S, Golda T, Monica M, Kreisler E, Fraccalvieri D, Frago R, Jaurrieta E. Generalized peritonitis due to perforated diverticulitis: Hartmann’s procedure or primary anastomosis? Int J Colorectal Dis 2011;26:377–84.
51. Demling RH. Nutrition, anabolism, and the wound healing process: an overview. Eplasty 2009;9:e9.
52. Syk I, Ågren MS, Adawi D, Jeppsson B. Inhibition of matrix metalloproteinases enhances breaking strength of colonic anastomoses in an experimental model. Br J Surg 2001;88:228–34.
53. Kobayashi T, Inoue T, Okada H, Kikuta T, Kanno Y, Nishida T, Takigawa M, Sugaya T, Suzuki H. Connective tissue growth factor mediates the profibrotic effects of transforming growth factor-beta produced by tubular epithelial cells in response to high glucose. Clin Exp Nephrol Internet 2005;9:114–21.
54. Fleisher AG, Evans KG, Nelems B, Finley RJ. Effect of routine fibrin glue use on the duration of air leaks after lobectomy. Ann Thorac Surg 1990;49:133–4.
55. Nomori H, Horio H, Morinaga S, Suemasu K. Gelatin-resorcinol-formaldehyde-glutaraldehyde glue for sealing pulmonary air leaks during thoracoscopic operation. Ann Thorac Surg 1999;67:212–6.
56. De Castro Durães L, Ferreira Ribeiro Durães E, De Campos Lobato LF, Gonçalves De Oliveira P, Batista De Sousa J. Correlation between bursting pressure and breaking strength in colonic anastomosis. Acta Cir Bras  2013;28:447–52.
57. Hoffmann NE, Siddiqui SA, Agarwal S, McKellar SH, Kurtz HJ, Gettman MT, Ereth MH. Choice of Hemostatic Agent Influences Adhesion Formation in a Rat Cecal Adhesion Model. J Surg Res 2009;155:77–81.
58. Stumpf M, Cao W, Klinge U, Klosterhalfen B, Kasperk R, Schumpelick V. Collagen distribution and expression of matrix metalloproteinases 1 and 13 in patients with anastomotic leakage after large-bowel surgery. Langenbeck’s Arch Surg 2002;386:502–6.
59. Desmoulière A, Chaponnier C, Gabbiani G. Tissue repair, contraction, and the myofibroblast. Wound Repair Regen.2005;13:7–12.
60. Steffensen B, Häkkinen L, Larjava H. Proteolytic events of wound-healing - Coordinated interactions among matrix metalloproteinases (MMPs), integrins, and extracellular matrix molecules. Crit Rev Oral Biol Med 2001;12:373–98.
61. van Der Ham AC, Kort WJ, Weijma IM, Van Ingh HFGMD, Jeekel J. Effect of fibrin sealant on the healing colonic anastomosis in the rat. Br. J. Surg.1991;78:49–53.
62. Ekmektzoglou KA, Zografos GC, Kourkoulis SK, Dontas IA, Giannopoulos PK, Marinou KA, Poulakou M V., Perrea DN. Mechanical behavior of colonic anastomosis in experimental settings as a measure of wound repair and tissue integrity. World J Gastroenterol 2006;12:5668–73.
63. Oxlund H, Christensen H, Seyer-Hansen M, Andreassen TT. Collagen deposition and mechanical strength of colon anastomoses and skin incisional wounds of rats. J Surg Res 1996;66:25–30.
64. Loncar MB, Al-azzeh E, Sommer PSM, Marinovic M, Schmehl K, Kruschewski M, Blin N, Stohwasser R, Gött P, Kayademir T. Tumour necrosis factor alpha and nuclear factor kappaB inhibit transcription of human TFF3 encoding a gastrointestinal healing peptide. Gut 2003;52:1297–303.
65. Schreinemacher MH, Bloemen JG, Van Der Heijden SJ, Gijbels MJ, Dejong CH, Bouvy ND. Collagen fleeces do not improve colonic anastomotic strength but increase bowel obstructions in an experimental rat model. Int J Colorectal Dis 2011;26:729–35.
66. Iizuka M, Konno S. Wound healing of intestinal epithelial cells. World J Gastroenterol 2011;17:2161–71.
67. Willis S, Stumpf M. Leakages after surgery of the lower gastrointestinal tract. Chirurg 2004;75:1071–8.
68. Rudinskaite G, Tamelis A, Saladzinskas Z, Pavalkis D. Risk factors for clinical anastomotic leakage following the resection of sigmoid and rectal cancer. Medicina (Kaunas) 2005;41:741–6.
69. Munireddy S, Kavalukas SL, Barbul A. Intra-abdominal Healing: Gastrointestinal Tract and Adhesions. Surg. Clin. North Am.2010;90:1227–36.
70. Steed DL. Wound-healing trajectories. Surg. Clin. North Am.2003;83:547–55.
71. Gantwerker EA, Hom DB. Skin: Histology and physiology of wound healing. Clin. Plast. Surg.2012;39:85–97.
72. Liu L, Kubes P. Molecular mechanisms of leukocyte recruitment: Organ-specific mechanisms of action. Thromb. Haemost.2003;89:213–20.
73. Mammen JM V., Matthews JB. Mucosal repair in the gastrointestinal tract. Crit Care Med  2003;31:S532–7.
74. Fukai T, Takeda A, Uchinuma E. Wound healing in denervated rat skin. Wound Repair Regen 2005;13:175–80.
75. Tidball JG. Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol 2005;288:R345-53.
76. Singh S, Young A, McNaught CE. The physiology of wound healing. Surg. (United Kingdom) 2017;35:473–7.
77. Pramateftakis MG, Kanellos D, Mantzoros I, Despoudi K, Raptis D, Angelopoulos S, Koliakos G, Zaraboukas T, Lazaridis C. Intraperitoneally administered irinotecan with 5-fluorouracil impair wound healing of colonic anastomoses in a rat model: an experimental study. Tech Coloproctol  2011;15 Suppl 1:S121-5.
78. Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev 2003;83:835–70.
79. Li W, Dasgeb B, Phillips T, Li Y, Chen M, Garner W, Woodley DT. Wound-healing perspectives. Dermatol. Clin.2005;23:181–92.
80. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Repair Regen.2008;16:585–601.
81. Gottrup F, Holstein P, Jørgensen B, Lohmann M, Karlsmark T. A new concept of a multidisciplinary wound healing center and a national expert function of wound healing. Arch Surg 2001;136:765–72.
82. Penhallow K. A review of studies that examine the impact of infection on the normal wound-healing process. J Wound Care  2005;14:123–6.
83. Diegelmann RF. Wound healing: an overview of acute, fibrotic and delayed healing. Front Biosci  2004;9:283.
84. Enoch S, Price P. Cellular, molecular and biochemical differences in the pathophysiology of healing between acute wounds, chronic wounds and wounds in the aged. World Wide Wounds2004;2005.
85. Baum CL, Arpey CJ. Normal cutaneous wound healing: clinical correlation with cellular and molecular events. Dermatol Surg 2005;31:674–86; discussion 686.
86. Thomas DW, Harding KG. Wound healing. Br J Surg 2002;89:1203–5.
87. Ramasastry SS. Acute wounds. Clin. Plast. Surg.2005;32:195–208.
88. Monaco JAL, Lawrence WT. Acute wound healing: An overview. Clin. Plast. Surg.2003;30:1–12.
89. Murray B, Wilson DJ. A study of metabolites as intermediate effectors in angiogenesis. Angiogenesis 2001;4:71–7.
90. Shimizu T, Nishihira J, Watanabe H, Abe R, Honda A, Ishibashi T, Shimizu H. Macrophage migration inhibitory factor is induced by thrombin and factor Xa in endothelial cells. J Biol Chem 2004;279:13729–37.
91. Deiters U, Barsig J, Tawil B, Mühlradt PF. The macrophage-activating lipopeptide-2 accelerates wound healing in diabetic mice. Exp Dermatol 2004;13:731–9.
92. Clark RAF, An JQ, Greiling D, Khan A, Schwarzbauer JE. Fibroblast Migration on Fibronectin Requires Three Distinct Functional Domains. J Invest Dermatol 2003;121:695–705.
93. Bouma BN, Mosnier LO. Thrombin Activatable Fibrinolysis Inhibitor (TAFI) at the interface between coagulation and fibrinolysis. In: Pathophysiology of Haemostasis and Thrombosis. 2003. page 375–81.
94. Wilson DA. Principles of early wound management. Vet. Clin. North Am. - Equine Pract.2005;21:45–62.
95. Toy LW. Matrix metalloproteinases: their function in tissue repair. J Wound Care 2005;14:20–2.
96. Salmela MT, Pender SLF, Karjalainen-Lindsberg ML, Puolakkainen P, MacDonald TT, Saarialho-Kere U. Collagenase-1 (MMP-1), matrilysin-1 (MMP-7), and stromelysin-2 (MMP-10) are expressed by migrating enterocytes during intestinal wound healing. Scand J Gastroenterol 2004;39:1095–104.
97. Theoret CL. The pathophysiology of wound repair. Vet. Clin. North Am. - Equine Pract.2005;21:1–13.
98. Midwood KS, Williams LV, Schwarzbauer JE. Tissue repair and the dynamics of the extracellular matrix. Int. J. Biochem. Cell Biol.2004;36:1031–7.
99. Stumpf M, Cao W, Klinge U, Klosterhalfen B, Kasperk R, Schumpelick V. Collagen distribution and expression of matrix metalloproteinases 1 and 13 in patients with anastomotic leakage after large-bowel surgery. Langenbeck’s Arch Surg 2002;386:502–6.
100. Faruquzzaman, Mazumder SK. The healing role of erythropoietin in the obstructive vs nonobstructive left colonic anastomosis. Bratislava Med J 2009;110:530–5.
101. Hendriks T, Hesp WLEM, Klompmakers AA, Lubbers EJC, de Boer HHM. Solubility of tissue hydroxyproline in experimental intestinal anastomoses. Exp Mol Pathol 1985;43:253–9.
102. Hashimoto T, Suzuki Y, Tanihara M, Kakimaru Y, Suzuki K. Development of alginate wound dressings linked with hybrid peptides derived from laminin and elastin. Biomaterials 2004;25:1407–14.
103. Kosir MA, Quinn CCV, Wang W, Tromp G. Matrix glycosaminoglycans in the growth phase of fibroblasts: More of the story in wound healing. J Surg Res 2000;92:45–52.
104. Türlü C, Willumsen N, Marando D, Schjerling P, Biskup E, Hannibal J, et al. A human cellular model for colorectal anastomotic repair: The effect of localization and transforming growth factor-β1 treatment on collagen deposition and biomarkers. Int J Mol Sci. 2021 Feb 2;22(4):1–17. 
105. Strowitzki MJ, Kimmer G, Wehrmann JS, Ritter AS, Radhakrishnan P, Opitz VM, et al. Inhibition of HIF-prolyl hydroxylases improves healing of intestinal anastomoses. JCI Insight. 2021 Apr 22;6(8). 
106. Wiegerinck M, Hyoju SK, Mao J, Zaborin A, Adriaansens C, Salzman E, et al. Novel de novo synthesized phosphate carrier compound ABA-PEG20k-Pi20 suppresses collagenase production in Enterococcus faecalis and prevents colonic anastomotic leak in an experimental model. Br J Surg. 2018 Sep 1;105(10):1368–76. 
107. Krarup PM, Eld M, Jorgensen LN, Hansen MB, Ågren MS. Selective matrix metalloproteinase inhibition increases breaking strength and reduces anastomotic leakage in experimentally obstructed colon. Int J Colorectal Dis. 2017 Sep 1;32(9):1277–84. 
108. Lorenzi T, Trombettoni MMC, Ghiselli R, Paolinelli F, Gesuita R, Cirioni O, et al. Effect of omiganan on colonic anastomosis healing in a rat model of peritonitis, American Journal of Translational Research. 2017;9(7):3374–86. 
109. Despoudi K, Mantzoros I, Ioannidis O, Cheva A, Antoniou N, Konstantaras D, et al. Effects of albumin/glutaraldehyde glue on healing of colonic anastomosis in rats. World J Gastroenterol. 2017 Aug 21;23(31):5680–91.

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    Starting on April 13th 2016, all articles selected for a peer-review will receive the post peer-review decision within ~10 days. The initial pre-screening time will remain the same (48h from the submission of the manuscript). This decision will significantly accelerate the publication, with no effect on the quality of the peer-review process.

  • 2016, February | Manuscript submission

    Discoveries is commited to excellence, quality and high editorial standards. We are receiving an increasing number of manuscripts for which the identity of the authors/corresponding author can't be verified. Please NOTE that ALL these articles were and will be immediately REJECTED. Indicating an institutional email address is the easiest way to overcome this problem! Moreover, we do not accept any pressure on our editorial board to accept a manuscript. This results in a prompt rejection of the article.

    Editorial Policies
  • 2016, January | Main Objective

    After reaching all proposed milestones until now (including being indexed by Google Scholar in 2014), Discoveries' next Aim is PubMed indexing of all its articles (already published and upcoming). There will be no charge for the submission or publication of articles before Discoveries is indexed.

  • 2015, August | Discoveries - on PubMed

    We are happy to announce that our first Discoveries articles were included in PMC and PubMed. More articles (submitted by NIH funded authors) are now processed for being included.

    Discoveries articles now on PubMed
  • 2015, April | Special Issue

    DISCOVERIES published the SPECIAL ISSUE entitled "INFLAMMATION BETWEEN DEFENSE AND DISEASE: Impact on Tissue Repair and Chronic Sickness".

    Special Issue on "Inflammation"
  • 2015 | Ischemia Collection

    DISCOVERIES launched a call for papers for a Collection of Articles with focus on "ISCHEMIA". If you are interested to submit a manuscript, please contact us at info@discoveriesjournals.org

  • 2014, September | Special Issue

    DISCOVERIES just publish the SPECIAL ISSUE entitled "CELL SECRETION & MEMBRANE FUSION" in September 2014. Initially scheduled for publication between October 2014-March 2015, this issue was successfully published earlier than scheduled. 

    Special Issue
  • 2014, April | Indexed by Google Scholar

    All our published articles are now indexed by Google Scholar! First citations to Discoveries articles are included! Search for the article's title (recommended) or the authors:

    Google Scholar Search
  • 2014 | DISCOVERIES

    DOIs (Digital Object Identifiers) are now assigned to all our published manuscripts in Discoveries. DOI uniquely identifies an article and is provided by CrossRef.

    CrossRef
  • 2013, July | Manuscript Submission

    Submit your manuscript FREE, FAST and EASY ! (in less than 1 minute)! There are NO fees for the manuscript submission or publishing of the accepted manuscripts.
    read more

  • 2013, July | DISCOVERIES

    We are now ACCEPTING MANUSCRIPTS for publishing in DISCOVERIES. We aim publishing a small number of high impact experimental articles & reviews (around 40/year) to maintain a high impact factor. Domains of interest: all areas related to Medicine, Biology and Chemistry ...

    read more
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