RESUMO
Abdominal surgeries can sometimes lead to the formation of intra-abdominal adhesions, which may result in severe complications. Despite the availability of several diagnostic procedures, thermography has not been used for identifying intra-abdominal adhesions. Therefore, the objective of the current study was to assess abdominal temperature changes in rats with experimentally induced intra-abdominal adhesions. A total of 48 female rats were randomly divided into 4 groups (n = 12 each): Control (Group C), Laparotomy (Group Lap), Peritoneal Button Creation (Group PBC), and Uterus horn (Group UH). Skin temperature of abdominal region was measured before the procedure (T0) and daily thereafter until day 7 (T7). On day 7, all rats were euthanized for macroscopic evaluation, adhesion scoring, histopathological, immunohistochemical and immunofluorescence analyses. Significant differences were observed between Group C and Group PBC and Group UH at T5, while at T6 and T7, there was a difference between Group C and Group Lap, Group PBC, and Group UH in abdominal skin temperature (P < 0.05). The highest level of inflammation, angiogenesis, IL-1ß, and VEGF were observed in Group PBC followed by Group UH, Group Lap, and Group C (P < 0.05). There was a significant difference in adhesion formation between Group C and Groups Lap, PBC, and UH (P = 0.02). However, no significant difference was found in adhesion scores between Groups Lap, PBC, and UH (P = 0.25). A significant difference was found in mean abdominal skin temperature between adhesion scores 4 and 0, 1, and 2 (P < 0.05), while no significant difference was observed between adhesion scores 3 and 4 (P > 0.05). In conclusion, the current study suggests that the presence of intra-abdominal adhesions is associated with an increase in abdominal temperature, and this increase is correlates with the severity of adhesion.
Assuntos
Termografia , Animais , Aderências Teciduais , Termografia/métodos , Feminino , Ratos , Abdome , Temperatura Cutânea , Interleucina-1beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ratos Wistar , Raios InfravermelhosRESUMO
A light-activated chemically reactive fibrous patch (ChemPatch) with tissue adhesion and wound healing activity was developed for preventing postoperative peritoneal adhesion. ChemPatch was constructed by an integrative electrospinning fabrication strategy, generating multifunctional PCL-NHS fibers encapsulating antioxidant curcumin and MnO2 nanoparticles. ChemPatch exhibited excellent photothermal conversion, which not only reformed the physical state to match the tissue but also improved conjugation between ChemPatch and tissues, allowing for strong attachment. Importantly, ChemPatch possessed good antioxidant and radical scavenging activity, which protected cells in an oxidative microenvironment and improved tissue regeneration. Particularly, ChemPatch acted as a multifunctional barrier and could not only promote reepithelialization and revascularization in wound defect model but simultaneously ameliorate inflammation and prevent postoperative peritoneal adhesion in a mouse cecal defect model. Thus, ChemPatch represents a dual-active bioadhesive barrier for reducing the incidence and severity of peritoneal adhesions.
Assuntos
Cirurgia Geral , Complicações Pós-Operatórias , Telas Cirúrgicas , Aderências Teciduais , Cicatrização , Cavidade Peritoneal/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Luz , Telas Cirúrgicas/normas , Cirurgia Geral/instrumentação , Cirurgia Geral/métodos , Curcumina/uso terapêutico , Nanopartículas/química , Nanopartículas/uso terapêutico , Óxido de Magnésio/uso terapêutico , Resultado do Tratamento , Camundongos Endogâmicos ICR , Animais , Camundongos , Linhagem CelularRESUMO
BACKGROUND: Although low-dose carbon monoxide (CO) administration has been shown to have an anti-fibrotic effect in various fibrotic diseases, its effects on peritoneal adhesion (PA), one of the postoperative complications, are not elucidated. In this study, the effect of CO-releasing tricarbonyldichlororuthenium (II) dimer (CORM-2) administration on the formation of PA and the underlying factors of its potential effect were investigated. METHODS AND RESULTS: After the induction of PA, rats were divided into four groups with 8 rats in each group. The rats received either (i) dimethyl sulfoxide:saline solution (1:10) as a vehicle, (ii) 2.5 mg/kg CORM-2, (iii) 5 mg/kg CORM-2, or (iv) inactive (i) CORM (iCORM) intragastrically every day for a duration of 7 days. PA was not induced in rats (n = 8) designated as sham controls. Gross, histological, immunohistochemical and quantitative real-time polymerase chain reaction analyses were performed to evaluate the effectiveness of CORM-2 administration. Gross analysis showed that CORM-2 administration reduced PA formation compared to rats treated with vehicle. Histological and immunohistochemical examinations showed that increased collagen deposition, myofibroblast accumulation, microvessel density, and M1 macrophage count in the peritoneal fibrosis area of vehicle-treated rats decreased following CORM-2 treatments. PCR analyses showed that CORM-2 treatments decreased hypoxia-induced Hif1a, profibrotic Tgfb1, ECM components Col1a1 and Col3a1, collagen degradation suppressor Timp1, fibrinolysis inhibitor Serpine1, and pro-inflammatory Tnf mRNA expressions, while increasing the M2 macrophage marker Arg1 mRNA expression. CONCLUSIONS: These results suggested that CORM-2 administration reduces PA formation by affecting adhesiogenic processes such as pro-inflammatory response, fibrinolytic system, angiogenesis and fibrogenesis.
Assuntos
Monóxido de Carbono , Dimetil Sulfóxido , Animais , Ratos , Monóxido de Carbono/farmacologia , Hipóxia , RNA MensageiroRESUMO
PURPOSE: Endometriosis is a benign, but potentially serious gynaecological condition in terms of abdominal pain and impaired fertility. Laparoscopic excision techniques are considered the therapeutic standard. HybridAPC is presented as a novel technique for the non-contact thermal ablation of peritoneal endometriosis with simultaneous protection of the underlying thermosensitive structures by creating a needle-free elevated fluid cushion which enables a safer exposure and distance, as well as potentially improved peritoneal conditioning prior to APC. METHODS: In this prospective randomized clinical trial, 39 patients with 132 superficial endometriotic lesions in total were treated with HybridAPC or sharp excision in an initial laparoscopic procedure according to randomization. In a second-look laparoscopy, adhesion formation was rated macroscopically. Histologic samples were taken from previously treated areas for evaluation of eradication rate. RESULTS: The eradication rate was not significantly different between HybridAPC treatment and sharp excision (65 vs. 81%, p = .55). Adhesions formed in 5% of HybridAPC-treated lesions and in 10% after sharp excision (p = .49). HybridAPC treatment was significantly faster than sharp excision (69 vs. 106 s, p < .05). No intra- and postoperative complications were registered. CONCLUSION: This clinical trial demonstrates the feasibility of this novel surgical technique with a promising impact on adhesion prevention. Compared to sharp excision, HybridAPC is likely to be a safe, tissue-preserving, and fast method for the treatment of peritoneal endometriosis.
Assuntos
Endometriose , Laparoscopia , Feminino , Humanos , Endometriose/cirurgia , Endometriose/patologia , Coagulação com Plasma de Argônio , Estudos Prospectivos , Peritônio/patologia , Laparoscopia/métodos , Aderências Teciduais/prevenção & controle , Aderências Teciduais/cirurgia , Aderências Teciduais/patologiaRESUMO
BACKGROUND: Peritoneal adhesion formation is an inevitable consequence of abnormal repair of the peritoneum following different peritoneal injuries of intra-abdominal operations with the subsequent morbidity that they represent. Vast efforts have been made to elucidate the cause and prevent the development of abdominal adhesions. The aim of our study is to compare the capability of colchicine versus diphenhydramine (DPH) and methylprednisolone (MP), and also prednisolone in adhesion prevention. METHODS: Sixty-one male Wistar stock rats were divided into four groups. The first group attended as the control group. Groups 2, 3, and 4 received oral combination of MP + DPH solution (20 mg/kg), colchicine (0.02 mg/kg), and prednisolone (1 mg/ kg), respectively. Adhesion bands were induced by standardized abrasion of the peritoneum through a midline laparotomy. All rats were sacrificed on the 15th-day post medication administration and the subjects underwent an exploratory laparotomy. The presence of adhesions was evaluated with the modified using Nair's classification. RESULTS: The proportion of the control group with substantial adhesion bands (73.3%) was significantly higher than that of the MP + DPH (13.3%), colchicine (33.3%), and prednisolone (31.3%) groups. There were significant differences between the scores of the control and the MP + DPH, colchicine, and prednisolone groups (P = 0.001, 0.028, and 0.019, respectively). There was no statistically significant difference to favor colchicine against MP + DPH (P = 0.390) or MP + DPH against prednisolone (P = 0.394). CONCLUSIONS: Both colchicine and combination of DPH + MP prevented postoperative abdominal adhesions separately in our study. However, the lowest adhesion formation rate was observed in the DPH + MP group, even lower than the prednisolone group.
Assuntos
Difenidramina , Doenças Peritoneais , Ratos , Masculino , Animais , Difenidramina/farmacologia , Ratos Wistar , Colchicina/uso terapêutico , Colchicina/farmacologia , Peritônio/cirurgia , Peritônio/patologia , Doenças Peritoneais/patologia , Metilprednisolona/uso terapêutico , Aderências Teciduais/etiologia , Aderências Teciduais/prevenção & controle , Complicações Pós-Operatórias/prevenção & controleRESUMO
BACKGROUND: Intraperitoneal adhesion formation is a significant problem following surgeries, resulting in substantial clinical and economic consequences. Glycyrrhiza glabra has several pharmacological properties consisting of anti-inflammatory, anti-microbial, anti-oxidant, anti-cancer, and immunomodulatory activities. AIM: Therefore, we aimed to investigate the impacts of G. glabra on the development of post-operative abdominal adhesion in a rat model. METHODS: Male Wistar rats weighing 200-250 g were divided into six groups (n = 8): Group 1: normal group (non-surgical), and the surgical groups including Group 2: control group received the vehicle, Group 3: G. glabra 0.5% w/v, Group 4: G. glabra 1% w/v, Group 5: G. glabra 2% w/v, and Group 6: dexamethasone, 0.4% w/v. The intra-abdominal adhesion was performed utilizing soft sterilized sandpaper on one side of the cecum, and the peritoneum was slightly washed with 2 ml of the extract or vehicle. In addition, macroscopic examination of adhesion scoring and the levels of inflammatory mediators [interferon (IFN)-γ, prostaglandin E2 (PGE2)], fibrosis markers [interleukin (IL)-4, transforming growth factor (TGF)-êµ], and oxidative factors [malondialdehyde (MDA), nitric oxide metabolites (NO), and reduced glutathione (GSH)] were evaluated. In vitro toxicities were also done on mouse fibroblast L929 and NIH/3T3 cell lines. RESULTS: We found higher levels of adhesion (P < 0.001), IFN-γ(P < 0.001), PGE2(P < 0.001), IL-4(P < 0.001), TGF-ß(P < 0.001), MDA(P < 0.001), and NO(P < 0.001), and lower levels of GSH(P < 0.001) in the control group. In contrast, G. glabra concentration dependent and dexamethasone alleviated the levels of adhesion (P < 0.05), inflammatory mediators (P < 0.001-0.05), fibrosis (P < 0.001-0.05), and oxidative (P < 0.001-0.05) factors, while propagating the anti-oxidant marker (P < 0.001-0.05) in comparison to the control group. Results also showed that the extract did not significantly reduce cell viability up to 300 µg/ml (P > 0.05). CONCLUSION: G. glabra could concentration-dependently mitigate peritoneal adhesion formation through its anti-inflammatory, anti-fibrosis, and anti-oxidant properties. However, further clinical investigations are required to approve that G. glabra may be a promising candidate against post-surgical adhesive complications.
Assuntos
Glycyrrhiza , Lavagem Peritoneal , Camundongos , Ratos , Masculino , Animais , Ratos Wistar , Antioxidantes , Extratos Vegetais/farmacologia , Glycyrrhiza/metabolismo , Mediadores da Inflamação/metabolismo , DexametasonaRESUMO
INTRODUCTION: The development of peritoneal adhesions and the effects of different antiadhesion agents on such mechanisms are not fully understood. Temporary rises of the C-reactive protein (CRP) level have been reported after antiadhesion agent application. We present the changes of inflammation markers observed after use of a starch-based polysaccharide certified for adhesion prevention and hemostasis 4DF (4DryField® PH). METHOD: Retrospective comparative analysis of inflammation markers in 40 patients undergoing laparoscopic adhesiolysis with or without adhesion prophylaxis was conducted. Statistical comparisons were performed by means of paired or unpaired t tests (for normally distributed continuous data), Wilcoxon matched pairs signed-rank tests or Mann-Whitney tests (for not-normally distributed continuous data), Mantel-Cox tests (for continuous data describing time intervals), and Fisher's exact tests (for discrete data). RESULTS: The maximum post-operative CRP level was significantly elevated in the 4DF group (87 vs. 29%; p < 0.001), whereas leukocyte concentration and body temperature did not differ between groups. No signs of infection were detected in any of the patients and CRP levels spontaneously dropped to normal values within few days. No side effects or complications were observed in both groups. In second-look surgeries performed for other diagnoses 1-56 weeks after the first interventions, no remnants of 4DF or any peritoneal inflammatory reactions were observed. CONCLUSION: The starch-based polysaccharide 4DF can be considered safe and does not induce inflammatory reactions of clinical significance. Further studies regarding 4DF degradation are recommended and, apart from macrophage migration, could also examine corresponding markers such as IL-6 and PCT.
Assuntos
Doenças Peritoneais , Complicações Pós-Operatórias , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Aderências Teciduais/prevenção & controleRESUMO
BACKGROUND: Postoperative peritoneal adhesion (PPA) is regarded as fibrous bands connecting both injured abdominal wall and organs or adjacent tissues. It is associated with T helper (Th)1 and Th2 differentiation. However, the critical role of the immunopathogenesis of adhesion formation was precisely unknown. The aim of this study was to investigate the effect of a new agent polylactic acid (PLA) nanoparticles loaded with ligustrazine, that is, ligustrazine nanoparticles (LN) on PPA and identify the potential mechanism. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into the sham, model, LN, and sodium hyaluronate (SH) groups. The structure of LN, including entrapment efficiency (EE) and loading capacity (LC), and in vitro drug release were calculated. Adhesions were scored and the Masson's trichrome staining was used to determine the collagen deposition. The expressions of TLR4, MyD88, and NF-κB were measured by qRT-PCR, immunohistochemistry, and western blot assay. Moreover, Th1-related cytokines (IFN-γ, IL-12), Th2-related cytokines (IL-4, IL-6) in the cecum tissue and serum were conducted by ELISA. RESULTS: LN had good EE, LC, and control-release delivery characters with fairly uniform diameter and spherical morphology. It could effectively prevent adhesion formation after surgery. Besides, it could reduce collagen fibers accumulation, downregulate the expression levels of TLR4, MyD88, and NF-κB, and maintain Th1/Th2 balance. CONCLUSIONS: Ligustrazine nanoparticles had effective effects on Th1/Th2 balance by regulating TLR4/MyD88/NF-κB pathway in PPA rats. It may be served as a promising therapy on postoperative adhesion formation.
Assuntos
Nanopartículas , Pirazinas/uso terapêutico , Equilíbrio Th1-Th2 , Aderências Teciduais/tratamento farmacológico , Animais , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Aderências Teciduais/imunologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
Peritoneal adhesion represents a severe complication following surgery. Punica granatum (pomegranate) possesses several anti-oxidative and anti-inflammatory properties. Pomegranate peel extract (PPEx) can alleviate the production of various inflammatory factors and cytokines. Thus, we sought to evaluate the anti-adhesion effects of pomegranate in rats. Thirty male Wistar rats (6-week-old, 220 ± 20 g) were divided into five groups (n = 6): normal group without any surgical procedures, control group, and experimental groups receiving 2 ml of 1%, 2%, and 4% w/v PPEx, respectively. Peritoneal adhesions were examined macroscopically. Furthermore, we evaluated inflammatory cytokines levels [interleukin 6 (IL-6), and tumour necrosis factor-α (TNF-α)], growth factors [transforming growth factor- ß1 (TGF-ß1), and vascular endothelial growth factor (VEGF)], and oxidative stress parameters [nitric oxide metabolites (NO), and malondialdehyde (MDA), and glutathione (GSH)] using biochemical methods. Our results showed that the adhesion score and IL-6, TNF-α, TGF-ß1, VEGF, NO, and MDA levels were increased in the control group. In contrast, the GSH level was diminished in the control group compared with the normal group (P < 0.001). PPEx (1 and 2% w/v) markedly reduced all measured parameters compared with the control group (P < 0.001-0.05). PPEx may reduce peritoneal adhesion by alleviating adhesion formation, IL-6, TNF-α, TGF-ß1, VEGF, NO, and MDA, and stimulating anti-oxidative factors. Therefore, PPEx may be considered an appropriate candidate for the treatment of postoperative peritoneal adhesion.
Assuntos
Lavagem Peritoneal/métodos , Extratos Vegetais/administração & dosagem , Punica granatum , Complicações Pós-Operatórias/prevenção & controle , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Frutas , Masculino , Extratos Vegetais/isolamento & purificação , Complicações Pós-Operatórias/metabolismo , Ratos , Ratos Wistar , Aderências Teciduais/metabolismo , Aderências Teciduais/prevenção & controle , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Nanogels are attractive biocompatible materials that enable local delivery of multiple drugs. In this study, we demonstrated that 3D printing technology could be used to precisely construct nanogel discs carrying paclitaxel and rapamycin. 3D-printed nanogel disc rounds (12 mm diameter × 1 mm thickness) carrying paclitaxel and rapamycin evaded premature gelation during storage and the initial burst release of the drugs in the dissolution medium. In vivo 3D-printed nanogel discs permitted successful intraperitoneal delivery of paclitaxel and rapamycin in ES-2-luc ovarian-cancer-bearing xenograft mice. They were also shown to be therapeutically effective and capable of preventing postsurgical peritoneal adhesions in the treated xenograft mice.
Assuntos
Neoplasias Ovarianas/tratamento farmacológico , Poloxâmero/química , Impressão Tridimensional , Animais , Antibióticos Antineoplásicos/uso terapêutico , Feminino , Humanos , Camundongos , Paclitaxel/uso terapêutico , Sirolimo/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Postoperative peritoneal adhesions, fibrous bands formed in the peritoneal cavity following surgery, represent a common, challenging and costly problem faced by surgeons and patients, for which effective therapeutic options are lacking. Since aberrant inflammation is one of the key mechanisms underlying peritoneal adhesion formation, here we set out to study the role of developmental endothelial locus-1 (Del-1), which has been recently identified as an endogenous inhibitor of inflammation, in the formation of postoperative peritoneal adhesions using a mouse model of peritoneal adhesions induced by ischemic buttons. Del-1-deficient mice had a higher incidence of adhesions, and their adhesions had higher quality and tenacity scores. Del-1 deficiency also led to enhanced inflammation mediators and collagen production. Finally, Del-1 supplementation decreased the incidence and severity of postoperative peritoneal adhesions. Taken together, these results indicate a protective role for Del-1 in postoperative peritoneal adhesion formation.
Assuntos
Proteínas de Transporte/metabolismo , Doenças Peritoneais/metabolismo , Doenças Peritoneais/prevenção & controle , Peritônio/patologia , Aderências Teciduais/metabolismo , Aderências Teciduais/prevenção & controle , Animais , Proteínas de Ligação ao Cálcio , Moléculas de Adesão Celular , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Inflamação/patologia , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Camundongos Endogâmicos C57BL , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Complicações Pós-Operatórias/etiologia , Receptores Fc/metabolismo , Índice de Gravidade de Doença , Aderências Teciduais/etiologiaRESUMO
BACKGROUND: Intra-abdominal adhesions and their complications following abdominal surgery are serious problems, with an incidence of 67-93%. Prevention of peritoneal adhesion formation may eliminate the need for surgical intervention, decreasing complications, morbidity, and cost. Bevacizumab is a recombinant monoclonal antibody which specifically binds vascular endothelial growth factor, an important cytokine in adhesion formation, and neutralizes its biological activity. We developed an experimental model in rats to determine the effect of bevacizumab in preventing adhesion formation and analyzed its effect both micro- and macroscopically. METHODS: We used 32. Wistar rats randomly divided into two groups: Group A (control) and Group B (bevacizumab), with 16 rats each. A modified cecum abrasion model was developed; 0.9% NaCl solution was administered intraperitoneally to Group A and bevacizumab to Group B. On day 15, adhesion formation was evaluated both macro- and microscopically. RESULTS: Both micro- and macroscopic adhesion grades in Group B were significantly lower than those of control Group A; macroscopic grades were 2.69 ± 0.95 and 0.69 ± 0.8, and microscopic grades were 2.25 ± 1.06 and 0.5 ± 0.52 for Groups A and B, respectively. CONCLUSIONS: Bevacizumab was effective in preventing intraperitoneal adhesion formation in our study; however, its inhibitory effects on embryogenesis and the hematopoietic, endocrine, and immune systems may limit its clinical use.
Assuntos
Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Inibidores da Angiogênese/farmacologia , Animais , Bevacizumab/farmacologia , Modelos Animais de Doenças , Feminino , Injeções Intraperitoneais , Ratos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: This study aimed to investigate the effects of ambroxol hydrochloride chitosan reduced the degree of peritoneal adhesion. METHODS: A total of 120 Sprague-Dawley (SD) rats were experimented, group A: the damaged peritoneal was covered with ambroxol hydrochloride chitosan, group B: chitosan membrane only, group C: nothing. Enzyme-linked immunosorbent assay (ELISA), western blotting, and immunohistochemistry (IHC) were used to observe the expression of TNF-α and NF-κB p65. RESULTS: TNF-α and NF-κB p65 in group A significantly decreased in comparison with the controls. IHC showed TNF-α and NF-κB p65 were significantly down-regulated in group A. Adhesion grade in the treatment group was significantly lower than in controls. CONCLUSION: Ambroxol hydrochloride chitosan reduced the degree of peritoneal adhesion.
Assuntos
Ambroxol/uso terapêutico , Quitosana/uso terapêutico , Expectorantes/uso terapêutico , Hemostáticos/uso terapêutico , Peritônio/patologia , Aderências Teciduais/prevenção & controle , Animais , Modelos Animais de Doenças , Intestinos/cirurgia , Ratos , Ratos Sprague-DawleyRESUMO
Postoperative peritoneal adhesion (PPA) is the most frequent complication after abdominal surgery. Current anti-adhesion strategies largely rely on the use of physical separating barriers creating an interface blocking peritoneal adhesion, which cannot reduce inflammation and suffers from limited anti-adhesion efficacy with unwanted side effects. Here, by exploiting the alternative activated macrophages to alleviate inflammation in adhesion development, a flexible graphene-composite-film (F-GCF) generating far-infrared (FIR) irradiation that effectively modulates the macrophage phenotype toward the anti-inflammatory M2 type, resulting in reduced PPA formation, is designed. The anti-adhesion effect of the FIR generated by F-GCF is determined in the rat abdominal wall abrasion-cecum defect models, which exhibit reduced incidence and area of PPA by 67.0% and 92.1% after FIR treatment without skin damage, significantly superior to the clinically used chitosan hydrogel. Notably, within peritoneal macrophages, FIR reduces inflammation reaction and promotes tissue plasminogen activator (t-PA) level via the polarization of peritoneal macrophages through upregulating Nr4a2 expression. To facilitate clinical use, a wirelessly controlled, wearable, F-GCF-based FIR therapy apparatus (GRAFT) is further developed and its remarkable anti-adhesion ability in the porcine PPA model is revealed. Collectively, the physical, biochemical, and in vivo preclinical data provide compelling evidence demonstrating the clinical-translational value of FIR in PPA prevention.
Assuntos
Modelos Animais de Doenças , Grafite , Complicações Pós-Operatórias , Animais , Aderências Teciduais/prevenção & controle , Ratos , Grafite/farmacologia , Complicações Pós-Operatórias/prevenção & controle , Suínos , Dispositivos Eletrônicos Vestíveis , Raios Infravermelhos , Ratos Sprague-DawleyRESUMO
Postoperative intra-abdominal adhesions represent a significant post-surgical problem. Its complications can cause a considerable clinical and cost burden. Herein, our study aimed to investigate the effect of Everolimus on peritoneal adhesion formation after inducing adhesions in rats. In this experimental study, adhesion bands were induced by intraperitoneal injection of 3 ml of 10% sterile talc solution in 64 male albino rats. The first group served as the control group. The second one received oral Prednisolone (1 mg/kg/day), the third received Everolimus (0.1 mg/kg/day), and group four received both drugs with similar dosages for four consecutive weeks. The formation of adhesion bands was qualitatively graded according to the Nair classification. The rats in the control group had extensive adhesions between the abdominal wall and the organs. Regarding substantial adhesion formation, 50% (8/16) of animals in the control group had substantial adhesions, while this rate in the groups receiving Prednisolone, Everolimus, and combination treatment was 31%, 31%, and 31%, respectively. Also, 68.75% (5/11) of the Prednisolone recipients had insubstantial adhesions, the same as Everolimus recipients, while in the combination group, 66.66% (10/15) rats had insubstantial adhesions. Everolimus demonstrated satisfactory results in reducing the rates of induced peritoneal adhesion in an experimental model, similar to Prednisolone and superior to a combination regime.
Assuntos
Everolimo , Prednisolona , Animais , Everolimo/farmacologia , Everolimo/administração & dosagem , Aderências Teciduais/tratamento farmacológico , Aderências Teciduais/prevenção & controle , Aderências Teciduais/patologia , Prednisolona/farmacologia , Prednisolona/administração & dosagem , Ratos , Masculino , Quimioterapia Combinada , Modelos Animais de Doenças , Peritônio/patologia , Peritônio/efeitos dos fármacos , Doenças Peritoneais/tratamento farmacológico , Doenças Peritoneais/patologia , Doenças Peritoneais/prevenção & controle , Doenças Peritoneais/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/tratamento farmacológicoRESUMO
Post-surgical abdominal adhesions, although poorly understood, are highly prevalent. The molecular processes underlying their formation remain elusive. This review aims to assess the relationship between neutrophil extracellular traps (NETs) and the generation of postoperative peritoneal adhesions and to discuss methods for mitigating peritoneal adhesions. A keyword or medical subject heading (MeSH) search for all original articles and reviews was performed in PubMed and Google Scholar. It included studies assessing peritoneal adhesion reformation after abdominal surgery from 2003 to 2023. After assessing for eligibility, the selected articles were evaluated using the Critical Appraisal Skills Programme checklist for qualitative research. The search yielded 127 full-text articles for assessment of eligibility, of which 7 studies met our criteria and were subjected to a detailed quality review using the Critical Appraisal Skills Programme (CASP) checklist. The selected studies offer a comprehensive analysis of adhesion pathogenesis with a special focus on the role of neutrophil extracellular traps (NETs) in the development of peritoneal adhesions. Current interventional strategies are examined, including the use of mechanical barriers, advances in regenerative medicine, and targeted molecular therapies. In particular, this review emphasizes the potential of NET-targeted interventions as promising strategies to mitigate postoperative adhesion development. Evidence suggests that in addition to their role in innate defense against infections and autoimmune diseases, NETs also play a crucial role in the formation of peritoneal adhesions after surgery. Therefore, therapeutic strategies that target NETs are emerging as significant considerations for researchers. Continued research is vital to fully elucidate the relationship between NETs and post-surgical adhesion formation to develop effective treatments.
Assuntos
Armadilhas Extracelulares , Armadilhas Extracelulares/metabolismo , Humanos , Aderências Teciduais/metabolismo , Aderências Teciduais/patologia , Neutrófilos/metabolismo , Complicações Pós-Operatórias/etiologia , Animais , Abdome/cirurgia , Abdome/patologiaRESUMO
Postoperative peritoneal adhesion (PPA) is a prevalent complication of abdominal surgery, posing a significant hindrance to postsurgical recovery. Although several strategies have been developed to alleviate and prevent adhesions, their efficacy remains unsatisfactory. For the first time, we studied the therapeutic effect and mechanism of our recently developed thermally stable oligonucleotide-based mimetics of hepatocyte growth factor (HGF DNA aptamer) to prevent PPA. The HGF DNA aptamer effectively inhibited canonical TGF-ß1 signaling transduction, partially suppressing mesothelial mesenchymal transition. Additionally, the aptamer, respectively, upregulated and downregulated the expression of tissue plasminogen activator and plasminogen activator inhibitor 1, thereby enhancing fibrinolytic activity. As a pleiotropic factor, the HGF DNA aptamer also enhanced the migratory and proliferative capacities of mesothelial cells. Finally, the aptamer demonstrated a higher level of effectiveness in preventing PPAs than the commercially available antiperitoneal adhesion barrier, Seprafilm. Due to its therapeutic benefits, excellent stability, biosafety, cost-effectiveness, and versatility, the HGF DNA aptamer demonstrates promise for preventing PPA in future clinical settings.
Assuntos
Aptâmeros de Nucleotídeos , Transição Epitelial-Mesenquimal , Fibrinólise , Fator de Crescimento de Hepatócito , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/farmacologia , Fator de Crescimento de Hepatócito/metabolismo , Aderências Teciduais/prevenção & controle , Humanos , Fibrinólise/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Teste de Materiais , Tamanho da Partícula , Complicações Pós-Operatórias/prevenção & controleRESUMO
The dried flower bud of Syzygium aromaticum L. (S. aromaticum) (Myrtaceae), cloves, have been used for their analgesic and anti-inflammatory activities. Peritoneal adhesion (PA) is the most common complication of abdominal and pelvic surgeries, which causes significant adverse effects and severe economic burden. The present study aimed to evaluate the preventive effect of S. extract (SAE) on PA formation in a rat model. Male Wistar 8-week-old rats were randomly divided into sham, control (received vehicle), and treatment (0.25%, 0.5%, and 1% w/v of SAE) groups. The adhesion and related factors were examined using the Nair scoring system and immunological and biochemical kits for the levels of inflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)-α], growth factors [transforming growth factor (TGF)-ß1 and vascular endothelial growth factor (VEGF)], oxidative [nitric oxide (NO) and malondialdehyde (MDA)], and anti-oxidative [glutathione (GSH)] factors. Our results figured out that the adhesion score and IL-6, TNF-α, TGF-ß1, VEGF, NO, and MDA levels were significantly increased, but the GSH level was decreased in the control group compared to the sham group (p < 0.001-0.05). On the other hand, the 0.25% SAE group had a lower adhesion score, and IL-6, TNF-α, TGF-ß1, VEGF, NO, and MDA levels were significantly decreased compared with the vehicle group, and the level of GSH was increased (p < 0.001-0.05). SAE could efficiently reduce adhesion score and regulate inflammatory cytokines, oxidative and anti-oxidative factors, and biomarkers of fibrosis and angiogenesis. Therefore, clove extract can be considered a potential candidate for PA management.
Assuntos
Citocinas , Syzygium , Animais , Masculino , Ratos , Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão , Citocinas/metabolismo , Fibrose , Glutationa/metabolismo , Interleucina-6/metabolismo , Estresse Oxidativo , Ratos Wistar , Syzygium/química , Syzygium/metabolismo , Fator de Crescimento Transformador beta1 , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Espectrometria de MassasRESUMO
INTRODUCTION: Postoperative peritoneal adhesions formed after abdominal surgery still continue to exist as an unresolved health problem. AIM: The aim of the present study is to examine whether omega -3 fish oil has a preventive effect on postoperative peritoneal adhesions. METHODS: Twenty-one female Wistar-Albino rats were separated into 3 groups (sham, control, and experimental group), each consisting of 7 rats. In sham group, only laparotomy was performed. Both in control and experimental group rats; the right parietal peritoneum and cecum were traumatized to form petechiae. Following this procedure, unlike the control group, the abdomen was irrigated with omega-3 fish oil in the experimental group. Rats were re-explored on the 14th postoperative day and adhesions were scored. Tissue samples and blood samples were taken for histopathological and biochemical analysis. RESULTS: None of the omega-3 fish oil given rats developed macroscopically postoperative peritoneal adhesion (P=0.005). Omega-3 fish oil formed an anti-adhesive lipid barrier on injured tissue surfaces. Microscopic evaluation revealed diffuse inflammation with excessive connective tissue and fibroblastic activity in control group rats while foreign body reactions were common in omega-3 given rats. The mean amount of hydroxyproline in samples from injured tissues was significantly lower in omega-3 given rats than in control rats. (P=0.004). CONCLUSION: Intraperitoneal application of omega-3 fish oil prevents postoperative peritoneal adhesions by forming an anti-adhesive lipid barrier on injured tissue surfaces. However, further studies are needed to determine whether this adipose layer is permanent or will be resorbed over time.
Assuntos
Doenças Peritoneais , Animais , Ratos , Feminino , Humanos , Ratos Wistar , Doenças Peritoneais/patologia , Doenças Peritoneais/prevenção & controle , Doenças Peritoneais/cirurgia , Peritônio/cirurgia , Laparotomia , Óleos de Peixe/farmacologia , Aderências Teciduais/patologia , Aderências Teciduais/prevenção & controle , Aderências Teciduais/cirurgia , Complicações Pós-Operatórias/prevenção & controleRESUMO
Peritoneal adhesion is a common abdominal surgical complication that induces abdominal haemorrhage, intestinal obstruction, infertility, and so forth. The high morbidity and recurrence rate of this disease indicate the need for novel therapeutic approaches. Here, we revealed the protective roles of tetrahydroberberrubine (THBru), a novel derivative of berberine (BBR), in preventing peritoneal adhesion and identified its underlying mechanism in vivo and in vitro. Abrasive surgery was used to create a peritoneal adhesion rat model. We found that THBru administration markedly ameliorated peritoneal adhesion, as indicated by a lowered adhesion score and ameliorated caecal tissue damage. By comparison, THBru exhibited more potent anti-adhesion effects than BBR at the same dose. Mechanistically, THBru inhibited inflammation and extracellular matrix (ECM) accumulation in the microenvironment of adhesion tissue. THBru suppressed the expression of inflammatory cytokines including interleukin-1ß (IL-1ß), IL-6, transforming growth factor ß (TGF-ß), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1), by regulating the transforming growth factor beta-activated kinase 1 (TAK1)/c-Jun N-terminal kinase (JNK) and TAK1/nuclear factor κB (NF-κB) signaling pathways. However, THBru promoted the activation of MMP-3 by directly blocking the TIMP-1 activation core and subsequently decreased collagen deposition. Taken together, this study identifies THBru as an effective anti-adhesion agent that regulates diverse mechanisms, thereby outlining its potential therapeutic implications for the treatment of peritoneal adhesion.