Keratinocyte growth factor: a new mesothelial targeted therapy to reduce postoperative pericardial adhesions☆

Lopes, Jaqueline B.; Dallan, Luís Alberto Oliveira; Filho, Sérgio Paulo Campana; Lisboa, Luiz Augusto Ferreira; Gutierrez, Paulo Sampaio; Moreira, Luíz Felipe Pinho; Oliveira, Sérgio Almeida de; Na, Stolf

doi:10.1016/j.ejcts.2008.09.046

Cited by 20 publications

(16 citation statements)

References 23 publications

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“…KGF can prevent and repair epithelium injuries of the skin, cornea, bladder, lungs, intestines, and liver through multiple approaches and multiple levels [32]. Lopes et al [13] employed KGF to prevent swine pericardial adhesions in their study and suggested that the use of growth factors targeting mesothelial cell proliferation or regeneration can reduce the severity of adhesions. However, it has not been reported that KGF can prevent peritoneal adhesions.…”

Section: Discussionmentioning

confidence: 99%

“…KGF has rarely been reported to prevent intra-abdominal adhesions by promoting mesothelial cell regeneration. KGF has been shown to improve mesothelial cell proliferation, which may enhance fibrinolytic activity to potentially suppress postoperative adhesions [13]. This study investigated whether the combined administration of KGF and sodium hyaluronate (HA) can prevent intra-abdominal adhesions in rats by promoting the orderly repair of the injured peritoneal mesothelial cell layer.…”

Section: Introductionmentioning

confidence: 99%

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Keratinocyte Growth Factor Combined with a Sodium Hyaluronate Gel Inhibits Postoperative Intra-Abdominal Adhesions

Wei

Zhou

Wang

et al. 2016

IJMS

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Postoperative intra-abdominal adhesion is a very common complication after abdominal surgery. One clinical problem that remains to be solved is to identify an ideal strategy to prevent abdominal adhesions. Keratinocyte growth factor (KGF) has been proven to improve the proliferation of mesothelial cells, which may enhance fibrinolytic activity to suppress postoperative adhesions. This study investigated whether the combined administration of KGF and a sodium hyaluronate (HA) gel can prevent intra-abdominal adhesions by improving the orderly repair of the peritoneal mesothelial cells. The possible prevention mechanism was also explored. The cecum wall and its opposite parietal peritoneum were abraded after laparotomy to induce intra-abdominal adhesion formation. Animals were randomly allocated to receive topical application of HA, KGF, KGF + HA, or normal saline (Control). On postoperative day 7, the adhesion score was assessed with a visual scoring system. Masson’s trichrome staining, picrosirius red staining and hydroxyproline assays were used to assess the magnitude of adhesion and tissue fibrosis. Cytokeratin, a marker of the mesothelial cells, was detected by immunohistochemistry. The levels of tissue plasminogen activator (tPA), interleukin-6 (IL-6), and transforming growth factor β1 (TGF-β1) in the abdominal fluid were determined using enzyme-linked immunosorbent assays (ELISAs). Western blotting was performed to examine the expression of the TGF-β1, fibrinogen and α-smooth muscle actin (α-SMA) proteins in the rat peritoneal adhesion tissue. The combined administration of KGF and HA significantly reduced intra-abdominal adhesion formation and fibrin deposition and improved the orderly repair of the peritoneal mesothelial cells in the rat model. Furthermore, the combined administration of KGF and HA significantly increased the tPA levels but reduced the levels of IL-6, tumor necrosis factor α (TNF-α) and TGF-β1 in the abdominal fluid. The expression levels of TGF-β1, fibrinogen and α-SMA protein and mRNA in the rat peritoneum or adhesion tissues were also down-regulated following the combined administration of KGF and HA. The combined administration of KGF and HA can significantly prevent postoperative intra-abdominal adhesion formation by maintaining the separation of the injured peritoneum and promoting mesothelial cell regeneration. The potential mechanism may be associated with rapid mesothelial cell repair in the injured peritoneum. This study suggests that combined administration of KGF and HA may be a promising pharmacotherapeutic strategy for preventing abdominal adhesions, which is worth further study, and has potential value in clinical applications.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Keratinocyte Growth Factor Combined with a Sodium Hyaluronate Gel Inhibits Postoperative Intra-Abdominal Adhesions

Wei

Zhou

Wang

et al. 2016

IJMS

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“…The prevention of postoperative adhesions to make sternal re-entry safer and to avoid its potentially associated lifethreatening complications has been a longstanding endeavor in cardiac surgery. The multiplicity of the proposed strategies, which range from the topical application of agents stimulating the pericardial fibrinolytic function by mesothelial cells 1 to the placement of resorbable 2 or nonresorbable 3 pericardial substitutes, clearly demonstrates that none of these strategies has proven convincing enough to gain wide clinical acceptance. On the basis of the study of Lassaletta, Chu, and Sellke, 4 it would seem that this list of compounds and devices can now be completed by.vodka.…”

mentioning

confidence: 99%

Vodka to prevent postoperative adhesions: Another unsuspected cardiac benefit of alcohol

Menasché

2012

The Journal of Thoracic and Cardiovascular Surgery

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“…Inúmeros problemas médicos são relatados como consequência da existência e da severidade das aderências pós-cirúrgicas, as quais dificultam futuras abordagens e adicionam maior morbidade e mortalidade às reoperações (Garrett e Matthews, 1989;Seeger, Kaelin et al, 1997;Bennett, Melanson et al, 2003;Lopes, Dallan et al, 2009).…”

Section: Carboximetilquitosanaunclassified

“…Fonte: http://www.medicinageriatrica.com.br/tag/pericardio/ Vários métodos têm sido investigados para prevenir ou diminuir a gravidade das aderências pós-cirúrgicas (Smith, 1968;Gallo, Artinano et al, 1982;Milgalter, Uretzky et al, 1985;Vandersalm, Okike et al, 1986), mas apenas após a utilização dos polímeros sintéticos ou dos biopolímeros é que os resultados se tornaram mais consistentes e reprodutíveis (Duncan, Yaacobi et al, 1988;Seeger, Kaelin et al, 1997;Krause, Zazanis et al, 2001;Lopes, Dallan et al, 2009 (Liu, Huang et al, 2007), epicloridrina (Demarchi, Debrassi et al, 2014), Lu, Sheng et al, 2009;Reves, Bumgardner et al, 2013), e genipina (Reves, Bumgardner et al, 2013;Bao, Chen et al, 2014), com o objetivo de controlar as propriedades físico-químicas e criar uma rede polimérica estável. Entretanto, agentes de reticulação sintéticos são altamente citotóxicos, apresentando baixa biocompatibilidade (Speer, Chvapil et al, 1980).…”

Section: Carboximetilquitosanaunclassified

Propriedades físico-químicas e mecânicas de membranas porosas de carboximetilquitosana e hidrogéis de quitosana para aplicação em engenharia de tecidos

Fiamingo¹

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The aim of this study was to produce and characterize porous membranes of carboxymethylchitosan and chitosan-based hydrogel with physicochemical and mechanical properties appropriate for applications in tissue engineering. For this, chitosans with different degrees of acetylation (4.0% < ̅̅̅̅ < 40%) and high viscosity average molecular weight ( ̅̅̅̅ > 750,000 g mol -1 ) were produced by application of consecutive processes of ultrasound-assisted deacetylation (USAD) of the beta-chitin extracted from squid pens (Doryteuthis spp.). The carboxymethylation of extensively deacetylated chitosan (Qs-3; ̅̅̅̅ = 4%) was carried out by reaction with monochloroacetic acid in isopropanol/aqueous NaOH, producing CMQs-0 sample ( ̅̅̅̅ ≈ 0.98; ̅̅̅̅ ≈ 190,000 g mol -1 ).The ultrasonic irradiation was employed to depolymerize the CMQs-0 samples by irradiation for 1 h and 3 h, resulting in CMQs-1 samples ( ̅̅̅̅ ≈ 94,000 g mol -1 ) and CMQs-3 ( ̅̅̅̅ ≈ 43,000 g mol -1 ), respectively. For the production of crosslinked membranes, genipin was added at different concentrations (1.0 x 10 -4 mol L -1 , 3.0 x 10 -4 mol L -1 and 5.0 x 10 -4 mol L -1 ) in the aqueous solutions of CMQs, which were poured into Petri dishes and the crosslinking reaction proceeded for 24 h. Then, the crosslinked membranes (M-CMQs) were lyophilized, neutralized, washed, and lyophilized again resulting in nine samples which were characterized by crosslinking degree ( ̅̅̅̅̅̅ ), swelling ratio ( ̅̅̅̅ ), morphology, mechanical properties and the susceptibility to enzymatic degradation by lysozyme. The crosslinking degree ( ̅̅̅̅̅̅ ) increased with increasing concentration of genipin used in the reaction, varying from ̅̅̅̅̅̅ ≈ 3.3% (M-CMQs-01) to ̅̅̅̅̅̅ ≈ 17.8% (M-CMQs-35). The SEM analysis showed that the crosslinked membranes M-CMQs are porous structures that have a higher apparent pores density with increasing values of ̅̅̅̅ and ̅̅̅̅̅̅ . However, the membranes prepared from high molecular weight CMQs ( ̅̅̅̅ ˃ 94,000 g mol -1 ) and low crosslinked ( ̅̅̅̅̅̅ ˂ 10%)showed superior mechanical properties in terms of ultimate tensile strength (˃ 170 kPa) and maximum elongation at break (˃ 40%). However, the more susceptible membrane to enzymatic degradation was prepared from low molecular weight CMQs ( ̅̅̅̅ ≈ 43,000 g mol -1 ) and low cross-linking degrees ( ̅̅̅̅̅̅ < 11%). Stable chitosan hydrogels without any external crosslinking agent was successfully achieved by inducing the gelation of a viscous chitosan solution with aqueous NaOH or gaseous NH 3 . The hydrogels produced from high molecular weight ( ̅̅̅̅̅ ≈ 640,000 g mol -1 ) and extensively deacetylated chitosan ( ̅̅̅̅ ≈ 2.8%) at polymer concentrations above ≈ 2.0% exhibited improved mechanical properties due to the increase of the chain entanglements and intermolecular junctions. The results also show that the physicochemical and mechanical properties of chitosan hydrogels can be controlled by varying their polymer concentration and by controlling the gelation kinetics, i.e. by using different gelation routes. The b...

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Keratinocyte growth factor: a new mesothelial targeted therapy to reduce postoperative pericardial adhesions☆

Abstract: The stimulation of pericardial cells with KGF reduced the intensity of postoperative adhesions and facilitated the re-operation. This study suggests that the mesothelial regeneration is the new horizon in anti-adhesion therapies.

Cited by 20 publications

References 23 publications

Keratinocyte Growth Factor Combined with a Sodium Hyaluronate Gel Inhibits Postoperative Intra-Abdominal Adhesions

Keratinocyte Growth Factor Combined with a Sodium Hyaluronate Gel Inhibits Postoperative Intra-Abdominal Adhesions

Vodka to prevent postoperative adhesions: Another unsuspected cardiac benefit of alcohol

Propriedades físico-químicas e mecânicas de membranas porosas de carboximetilquitosana e hidrogéis de quitosana para aplicação em engenharia de tecidos

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