Preservation of peritoneal fibrinolysis owing to decreased transcription of plasminogen activator inhibitor-1 in peritoneal mesothelial cells suppresses postoperative adhesion formation in laparoscopic surgery
ABSTRACT BACKGROUND: Postoperative adhesion formation is regulated by peritoneal fibrinolysis, which is determined by tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1). This study compared peritoneal fibrinolysis and adhesion formation after laparoscopic surgery (LAP) and open surgery (OP). METHODS: We divided 154 male rats into 3 groups after cecal cauterization: Control, no treatment; LAP, CO(2) pneumoperitoneum at 5 mmHg for 60 minutes; and OP, laparotomy for 60 minutes. Adhesions were quantified at day 7. The activity and mRNA level of tPA and PAI-1 were determined by enzyme-linked immunosorbent assay in plasma and peritoneal lavage and by real-time polymerase chain reaction in peritoneal mesothelial cells from omentum. We also examined peritoneal fibrinolysis in human gastric cancer patients treated with LAP (n = 14) or OP (n = 10). RESULTS: In the animal study, adhesion scores, PAI-1 activity in peritoneal lavage fluid, and PAI-1 mRNA levels in peritoneal mesothelium were significantly greater in the OP group than the control and LAP groups. In the human study, postoperative PAI-1 mRNA levels were significantly greater in the OP group than the LAP group. Additionally, PAI-1 mRNA levels and subsequent adhesion formation were induced by prolonged operative time in the OP group, but not the LAP group. CONCLUSION: Preservation of peritoneal fibrinolysis owing to decreased PAI-1 expression at the transcriptional level in peritoneal mesothelial cells is associated with suppression of postoperative adhesion formation in LAP. PAI-1 mRNA levels and subsequent adhesion formation were not induced by prolonged operative time in LAP. These results highlight the less invasiveness nature of LAP.
SourceAvailable from: Krina T Zondervan[Show abstract] [Hide abstract]
ABSTRACT: To standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the condition.
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ABSTRACT: Adhesion development is the most common sequelae of intra-abdominal and pelvic surgery and represents a significant, yet poorly understood, cause of morbidity among post-operative patients. It remains unclear, for example, exactly why adhesions form more frequently in certain tissues and/or patients, or at specific locations within them, as opposed to others. This review contributes to the growing knowledge pool by elucidating factors that potentially predispose to the development of adhesions. Given the strong correlation between a hypofibrinolytic state and adhesion formation, this review article will examine not only those factors that have been shown to directly predispose to adhesion development, but also those that are likely do so indirectly by means of altering the coagulation/fibrinolytic profile. A literature search was performed using the PubMed database for all relevant English language articles up to February 2014. All of the identified articles were reviewed with particular attention to predisposing factors to post-operative adhesion development. In addition, the reference lists of each article were reviewed to identify additional relevant articles. Various factors have been shown to directly increase the risk of post-operative adhesion development; namely, certain genetic polymorphisms in the interleukin-1 receptor antagonist, increased estrogen exposure, and endometriosis. In addition, numerous factors are known to increase the risk of fibrosis, therefore likely increasing the risk of adhesion development indirectly. These factors include genetic polymorphisms in plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor, diabetes mellitus, metabolic syndrome, hyperglycemia, obesity, depression, binge alcohol consumption, anti-Parkinsonian medications, oral hormone therapy, pregnancy, and cancer. The literature reviewed in this paper will help to direct future research aimed at understanding the mechanisms that underlie the association of certain factors with adhesion development. This information will be crucial in the creation of adequate preventative and treatment strategies. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: firstname.lastname@example.org.Human Reproduction Update 05/2015; DOI:10.1093/humupd/dmv021 · 8.66 Impact Factor
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ABSTRACT: This study concentrates on the development of biodegradable nanofiber membranes with controlled drug release to ensure reduced tissue adhesion and accelerated healing. Nanofibers of poly(lactic-co-glycolic acid) (PLGA) loaded with epigallocatechin-3-O-gallate (EGCG), the most bioactive polyphenolic compound in green tea, were electrospun. The physicochemical and biomechanical properties of EGCG-releasing PLGA (E-PLGA) nanofiber membranes were characterized by atomic force microscopy, EGCG release and degradation profiles, and tensile testing. In vitro antioxidant activity and hemocompatibility were evaluated by measuring scavenged reactive oxygen species levels and activated partial thromboplastin time, respectively. In vivo antiadhesion efficacy was examined on the rat peritonea with a surgical incision. The average fiber diameter of E-PLGA membranes was approximately 300-500 nm, which was almost similar to that of pure PLGA equivalents. E-PLGA membranes showed sustained EGCG release mediated by controlled diffusion and PLGA degradation over 28 days. EGCG did not adversely affect the tensile strength of PLGA membranes, whereas it significantly decreased the elastic modulus and increased the strain at break. E-PLGA membranes were significantly effective in both scavenging reactive oxygen species and extending activated partial thromboplastin time. Macroscopic observation after 1 week of surgical treatment revealed that the antiadhesion efficacy of E-PLGA nanofiber membranes was significantly superior to those of untreated controls and pure PLGA equivalents, which was comparable to that of a commercial tissue-adhesion barrier. In conclusion, the E-PLGA hybrid nanofiber can be exploited to craft strategies for the prevention of postsurgical adhesions.International Journal of Nanomedicine 08/2014; 9:4067-78. DOI:10.2147/IJN.S68197 · 4.20 Impact Factor