Postoperative Adhesion Formation Research Articles

Effect of ligustrazine nanoparticles on Th1/Th2 balance by TLR4/MyD88/NF-\u03baB pathway in rats with postoperative peritoneal adhesion

BackgroundPostoperative 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.MethodsTwenty-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.ResultsLN 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.ConclusionsLigustrazine 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.

MSC-derived immunomodulatory extracellular matrix functionalized electrospun fibers for mitigating foreign-body reaction and tendon adhesion

Adhesion formation during tendon healing remains a severe problem in clinical practice. Multiple factors contribute to postoperative adhesion formation, and macrophage-driven inflammation is thought to be greatly involved in this process. We hypothesize that reducing macrophage-mediated inflammation in the injured tendon by regulating M1 to M2 macrophage polarization may effectively inhibit adhesion formation. Here, we developed an acellular immunomodulatory biomaterial consisting of an electrospun polycaprolactone/silk fibroin (PCL/SF) composite fibrous scaffold functionalized with mesenchymal stem cell (MSC)-derived extracellular matrix (ECM). To enhance the immunoregulatory potential of MSCs, we performed inflammatory licensing with IFN-γ to obtain immunomodulatory ECM (iECM). Proteomic analyses of MSCs and their secreted ECM components from different culture conditions revealed the MSC-ECM molecular signatures and the potential mechanism of ECM immunoregulation. Then, the immunoregulatory potential of the iECM-modified scaffold was evaluated in vitro and in vivo. Relative to the PCL/SF fibrous scaffold, the iECM-functionalized scaffold facilitated M2 macrophage polarization and inhibited the expression of multiple cytokines (IL-1β, IL-6, CXCL11, IL-10, IL-1R2, and TGF-β1) in vitro, strongly suggesting the immunosuppressive ability of iECM derived from inflammatory licensed MSCs. Consistent with the in vitro findings, the results of rat subcutaneous implantation indicated that a markedly lower foreign-body reaction (FBR) was obtained in the PCL/SF-iECM group than in the other groups, as evidenced by thinner fibrotic capsule formation, less type I collagen production and more M2-type macrophage polarization. In the rat Achilles tendon injury model, the PCL/SF-iECM scaffold greatly mitigated tendon adhesion with clear sheath space formation between the tendon and the scaffold. These data highlight the immunomodulatory potential of iECM-functionalized fibrous scaffolds to attenuate FBR by modulating M2 macrophage polarization, thereby preventing tendon adhesion. Statement of significanceElectrospun PCL/SF fibrous scaffolds functionalized with ECM secreted by MSCs stimulated by inflammatory factor IFN-γ was developed that combined physical barrier and immunomodulatory functions to prevent tendon adhesion formation. PCL/SF micro-nanoscale bimodal fibrous scaffolds prepared by emulsion electrospinning possess high porosity and a large pore size beneficial for nutrient transport to promote intrinsic healing; moreover, surface modification with immunomodulatory ECM (iECM) mitigates the FBR of fibrous scaffolds to prevent tendon adhesion. The iECM-functionalized electrospun scaffolds exhibit powerful immunomodulatory potency in vitro and in vivo. Moreover, the iECM-modified scaffolds, as an anti-adhesion physical barrier with immunomodulatory ability, have an excellent performance in a rat Achilles tendon adhesion model. MSC secretome-based therapeutics, as an acellular regenerative medicine strategy, are expected to be applied to other inflammatory diseases due to its strong immunoregulatory potential.

Deletion of Calponin 2 Reduces the Formation of Postoperative Peritoneal Adhesions

Aim of the study: Postoperative peritoneal adhesions are a common cause of morbidity after surgery, resulting in multiple complications. Macrophage-mediated inflammation and myofibroblast differentiation after tissue injury play central roles in the pathogenesis and progression of adhesion formation. Calponin 2 is an actin cytoskeleton regulatory protein in endothelial cells, macrophages and fibroblasts that are key players in the development of fibrosis. Deletion of calponin 2 has been shown to attenuate inflammatory arthritis, atherosclerosis and fibrocalcification of the aortic valves. The present study investigated the effect of calponin 2 deletion on attenuating the formation of peritoneal adhesions in a mouse model for potential use as a new therapeutic target. Materials and methods: Sterile surgical procedures under general anesthesia were used on paired wild type (WT) and calponin 2 knockout (KO) mice to generate mild injury on the cecal and abdominal wall peritonea. Three and seven days post-operation, the mice were compared postmortem for the formation of peritoneal adhesions. Tissues at the adhesion sites were examined with histology and immunofluorescent studies for macrophage and myofibroblast activations. Results: Quantitative scoring demonstrated that calponin 2 KO mice developed significantly less postoperative peritoneal adhesions than that in WT mice. Calponin 2 deletion resulted in less infiltration of F4/80+ macrophages at the adhesion sites with less myofibroblast differentiation and collagen deposition than WT controls. Conclusions: The data show that deletion of calponin 2 effectively reduces postoperative peritoneal adhesion, presenting a novel molecular target for clinical prevention.

Hysteroscopic morcellation versus bipolar resection for removal of type 0 and 1 submucous myomas: A randomized trial

ObjectivesTo compare hysteroscopic morcellation with bipolar resection for the removal of submucous type 0 and 1 myomas, in terms of procedure time (primary outcome), adverse events, tissue availability, short term effectiveness and postoperative adhesion formation (secondary outcomes). Study designThe study was performed from May 2011 to May 2018 in the Catharina hospital (Eindhoven, the Netherlands) and the Ghent University hospital (Ghent, Belgium). Women with type 0 and 1 submucous myomas up to 3 cm were randomized to hysteroscopic morcellation with the TruClearTM 8.0 Tissue Removal System or to bipolar resection with a rigid 8.5-mm resectoscope. Skewed time variables were log-transformed and analyzed with the Student t-test. Multiple linear regression analysis was performed to assess the effect of myoma diameter on operating time. ResultsForty-five and 38 women were included in the hysteroscopic morcellation and resection group, respectively. The median operating time was significantly shorter for hysteroscopic morcellation compared with resection (9.2 min [interquartile range 5.6–14.4] versus 13.4 min [interquartile range 8.6–17.5], P = .04). In the morcellation group, operating time, corrected for the myoma diameter, was reduced by 26 % (95 % CI 5–43%; P = .02). The median setup time was significantly longer in the morcellation group (5.2 min [interquartile range 4.2–6.9] versus 3.8 min [interquartile range 3.3–5.3], P = .006). The median total procedure time was not significantly different between the two techniques (14.4 min [interquartile range 11.4–19.2] versus 17.3 [interquartile range 12.7–23.8], P = .18). Two procedures of the morcellation group were converted to bipolar resection because of the myoma hardness. Complete resection was found in 89 % of the morcellation group and 95 % of the resection group. Adverse events occurred in 3 patients of the morcellation group, namely a fluid deficit > 2500 mL with the need of potassium suppletion, an asystolic vasovagal response after conversion to resection and postoperative fever requiring antibiotics. Tissue was available for pathology analysis in all cases. Routine second-look hysteroscopy performed in one center showed no intrauterine adhesions. ConclusionOverall, there is no difference in total procedure time between hysteroscopic morcellation using the TruClearTM system compared to bipolar resection for the removal of smaller type 0 and 1 submucous myomas. Although hysteroscopic morcellation is faster, its setup time is longer. Calcified myomas can be challenging and fluid deficit remains a limiting factor.

Comparison of the effect of two anti-adhesion materials on the formation of postoperative adhesions after myomectomy – an experimental study on rabbit does

This study compares the effect of Hyalobarrier Gel and 4DryField® PH on the formation of postoperative adhesions after myomectomy in an experimental study on rabbit does. Thirty experimental animals were divided into three groups: group A – control, group B – use of 4DryField® PH, and group C – use of the Hyalobarrier Gel. A simulated myomectomy was performed in each group. The animals were euthanised 14 days after the procedure and the antiadhesive effect of the above-mentioned preparations was evaluated according to the criteria. Statistical evaluation clearly showed differences in the antiadhesive effect in the scoring systems for groups B and C compared to control group A at a high level of significance. We demonstrated an obvious, statistically confirmed antiadhesive effect of the Hyalobarrier Gel and 4DryField® PH in an experimental model of the rabbit uterus. Comparing both preparations, the Hyalobarrier Gel shows a higher level of effectiveness. Based on the results of the experiment, both preparations can be unambiguously recommended for routine practice.

Effects of 5-fluorouracil released from different prosthetic meshes on post-operative adhesion formation in rats.

Post-operative adhesion is a common problem in abdominal surgery. Especially, foreign materials are strong stimulus for the development of adhesions. The aim of this study was to investigate whether drug release material coated prosthetic mesh decreases intra-abdominal adhesion formation or not. 5-Fluorouracil (5-FU) releasing "chitosan gels" were loaded to polypropylene and polyglactin-910 grafts. Polypropylene, polyglactin-910 grafts, chitosan gel, and 5-FU-loaded polyglactin 910, polypropylene grafts were used to cover abdominal defects of rats which were created under sterile conditions (n=84). Each group was divided into two subgroups (n=6). Subgroups were sacrificed on the 7th and 30th days. The 7th day macroscopic examinations were similar. Polypropylene group was most adhesive group on the 30th day. There were less adhesions in chitosan gel and 5-FU-loaded groups. Capsule and capsule margins showed no difference on both the 7th and 30th days. Polypropylene-5-FU group and polypropylene-chitosan gel group showed significantly less macroscopic adhesions than polypropylene control group. Furthermore, polyglactin-910-chitosan gel group was less adhesive than polypropylene control group. This study showed that 5-FU decreases the adhesions but the dosage and release kinetics need further investigations.

A review of physiological and cellular mechanisms underlying fibrotic postoperative adhesion.

Postoperative adhesions (PA) are fibrotic tissues that are the most common driver of long-term morbidity after abdominal and pelvic surgery. The optimal drug or material to prevent adhesion formation has not yet been discovered. Comprehensive understanding of cellular and molecular mechanisms of adhesion process stimulates the design of future anti-adhesive strategies. Recently, disruption of peritoneal mesothelial cells were suggested as the 'motor' of PA formation, followed by a cascade of events (coagulation, inflammation, fibrinolysis) and influx of various immune cells, ultimately leading to a fibrous exudate. We showed that a variety of immune cells were recruited into adhesive peritoneal tissues in patients with small bowel obstruction caused by PA. The interactions among various types of immune cells contribute to PA development following peritoneal trauma. Our review focuses on the specific role of different immune cells in cellular and humoral mechanisms underpinning adhesion development.

Blockade of Tumor Necrosis Factor by Etanercept Prevents Postoperative Adhesion Formation in Mice.

Although adhesion formation is a frequent adverse event following intraperitoneal surgery, efficient prophylactic interventions have not yet been established. We recently reported that blockade of interleukin (IL)-6 prevented postoperative adhesion after cecum cauterization. Intriguingly, this intervention dampened tumor necrosis factor (TNF) induction in the injured serosa. Herein, we addressed whether TNF might be a key target and, if so, how TNF blockade rescued adhesion formation. Mice were administered an anti-TNF biologic (etanercept) on days -2 and -1 before and upon cecal cauterization. The adhesion scores were evaluated at day 7 postoperatively. Histological alterations were examined by immunochemistry/immunofluorescence studies. We incubated human neutrophils and mesothelial cell line cells with recombinant TNF in the presence of etanercept and measured transcript levels of cytokines and chemokines by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Etanercept rescued mice from adhesion formation, accompanied by a robust reduction of neutrophilia in the injured serosa. Immunofluorescence revealed a substantial formation of neutrophil extracellular traps (NETs) with the potential to induce tissue damage and profibrotic responses. In contrast, the etanercept-treated mice lacked NET formation. In addition, etanercept inhibited TNF-induced IL-6, TNF, and neutrophil-recruiting chemokines in neutrophils and mesothelial cells, a major cellular source of myofibroblasts in the adhesion band. Prophylactic administration of etanercept might be a potential strategy for preventing postoperative adhesion formation.

Novel Trilaminar Polymeric Antiadhesion Membrane Prevents Postoperative Pericardial Adhesion

Postoperative pericardial adhesion formation is a prominent cause of morbidity and death in cardiovascular surgery, but there is still no ideal prevention method, especially in redo cases. This study investigated a novel antiadhesion trilaminar polymeric film compared with the Gore PRECLUDE Pericardial Membrane (W. L. Gore & Associates, Flagstaff, AZ) and a negative control. Our novel trilaminar membrane is composed of polyvinyl alcohol (PVA) and carboxymethylcellulose (CMC). An established pericardial adhesion rabbit model was used to test the property of the membrane. After sternotomy, a portion of pericardium was resected and the epicardium was abraded. Rabbits (n= 24) were randomly assigned to 3 groups: control group, no trilaminar membrane or expanded polytetrafluoroethylene (ePTFE); ePTFE group, or trilaminar membrane group (PVA-CMC group). Evaluation of adhesion formation was performed by resternotomy 4 weeks after the operation. The degree of tissue adhesion surrounding the heart in the PVA-CMC group was significantly less than in the control (P < .01) and ePTFE (P < .05) groups. The inflammation score in group PVA-CMC was significantly lower than that in the ePTFE (P < .01) and control (P < .01) groups. The fibrosis score was significantly lower in group PVA-CMC than that in the ePTFE (P < .05) and control (P < .01) groups. The novel trilaminar membrane effectively reduced postoperative pericardial adhesions. The placement of the trilaminar membrane at the time of sternal closure provides a novel combination to minimize the extent and severity of pericardial adhesions while providing a physical barrier between the sternum and the cardiac structures.

Effects of Glycerol and Sodium Pentaborate Formulation on Prevention of Postoperative Peritoneal Adhesion Formation.

Background Postoperative peritoneal adhesions (PPA) are a serious problem for abdominal surgery. An effective remedy has not been found yet. New formulation of glycerol and sodium pentaborate may be able to solve the problem. Method Female Wistar albino rats were randomly assigned into four equal groups. The adhesion model was created on the caecum anterior wall and covered with 2 ml 0.9% NaCl, 3% glycerol, 3% sodium pentaborate, and 3% glycerol plus 3% sodium pentaborate solutions in the groups, respectively. Two weeks later, the rats were sacrificed. PPA were graded macroscopically and microscopically. Results Total adhesion scores of the 3% glycerol + 3% sodium pentaborate group were statistically different from the other groups for macroscopic and also microscopic evaluations (p < 0.001). Conclusion 3% glycerol plus 3% sodium pentaborate as a new formulation has preventive effects on PPA with a synergistic mechanism.

Cubital tunnel syndrome: a surgical modification to in situ decompression to improve results

BackgroundThe gold standard for surgical treatment of cubital tunnel syndrome is in situ decompression. However, this procedure does not come without complications. Subluxation of the ulnar nerve and ulnar nerve neuritis from adhesion formation remain 2 potential complications after this procedure. It has been shown in the literature that young, active, male patients are most likely to have these complications postoperatively. We have developed a modification to in situ decompression by developing a fascial turnover flap and using a porcine submucosa extracellular matrix (Axogen) to help reduce both ulnar nerve subluxation and adhesion formation postoperatively.MethodsThirteen patients underwent cubital tunnel surgery by the highlighted technique to prevent postoperative ulnar nerve subluxation and adhesion formation. Patient outcomes including elbow range of motion, functional status, paresthesia, and grip strength were recorded.ResultsOf the 13 patients, 10 had excellent results, 1 had a good result, and 2 required revision with anterior transposition of the nerve. The mean Mayo Elbow Performance Score of the 11 patients not needing revision was 92.7.ConclusionThe described surgical technique provides surgeons with the ability to directly decompress the ulnar nerve while decreasing postoperative complications such as instability and adhesion formation.

Sodium aescinate significantly suppress postoperative peritoneal adhesion by inhibiting the RhoA/ROCK signaling pathway

BackgroundAlthough mechanical barriers and modern surgical techniques have been developed to prevent postoperative adhesion formation, high incidence of adhesions still represents an important challenge in abdominal surgery. So far, there has been no available therapeutic drug in clinical practice. PurposeIn this study, we explored the efficacy of sodium aescinate (AESS) treatment against postoperative peritoneal adhesions, the potential molecular mechanism was also investigated. Study design and methodsSixty male Sprague-Dawley rats were randomly divided into 6 groups for the study: the blank, vehicle, positive control and three AESS administration groups (0.5, 1 and 2 mg/kg/d, intravenous administration for 7 days). Adhesions were induced by discretely ligating peritoneal sidewall. An IL-1β-induced HMrSV5 cell model was also performed to explore possible functional mechanism. ResultsThe results indicated that the incidence and severity of peritoneal adhesions were significantly lower in the AESS-treated groups than that in the vehicle and positive control group. AESS-treated groups showed that the secretion, activity, and expression of tPA in rat peritoneum were notably increased. The FIB levels in rat plasma were decreased. The immunohistochemical staining analysis demonstrated that collagen I and α-SMA deposition were significantly attenuated in AESS-treated peritoneal tissues. Besides, we found that AESS treatment reduced the protein levels of p-MYPT1. To further explore the mechanisms of AESS, both activator and inhibitors of RhoA/ROCK pathway were employed in this study. It was found that AESS-induced up-regulation of tPA was reversed by activator of ROCK, but the effects of ROCK inhibitors were consistent with AESS. ConclusionTaken together, the findings of in vivo and in vitro experiments proved that AESS could significantly suppress postoperative peritoneal adhesion formation through inhibiting the RhoA/ROCK signaling pathway. Our researches provide important pharmacological basis for AESS development as a potential therapeutic agent on peritoneal adhesions.

The effects of ozone therapy on postoperative adhesions and ovarian functions: An experimental study

Aim: Numerous methods are used to prevent the development of postoperative adhesion formation. There are few studies on the effects of ozone therapy on postoperative intraabdominal adhesions and ovarian functions. This study aimed to investigate the effects of ozone treatment on postoperative intraabdominal adhesions and ovarian roles in rats.Methods: Twenty female Wistar albino rats were randomly allocated into two groups as laparotomy (Group 1, n: 10) and laparotomy + intraperitoneal ozone (Group 2, n: 10). After laparotomy, parietal peritoneum, uterus and adnexal surfaces were scraped in both groups. Follicle-stimulating hormone (FSH), Estradiol (E2), Lactate Dehydrogenase (LDH), Urea, and Creatinine levels were measured, and histopathological evaluation was performed. Both groups were compared concerning histopathological and biochemical findings.Results: In the ozone-treated group, antioxidant levels (P=0.012) were significantly higher, and E2 levels (P=0.005) were substantially lower than the control group. There was no statistically significant difference between the two groups regarding FSH, Urea, Creatinine, and LDH (P=0.12, P=0.72, P=0.45, and P=0.79, respectively). Histopathologically, postoperative intraabdominal adhesion rates between the two groups were statistically similar.Conclusion: Although there was no statistically significant difference, ozone therapy had a decreasing effect on severe fibrosis and congestion rates. Although there was no difference in FSH, low levels of E2 in Group 2 suggest that ozone treatment may have a protective effect on the ovaries. However, further studies are needed concerning adhesion formation and the impact on ovarian functions.

Practical considerations in the use of a porcine model (Sus scrofa domesticus) to assess prevention of postoperative peritubal adhesions.

Infertility has been a common postoperative problem caused by peritoneal adhesions. Since several prophylactic agents have recently shown promising preliminary results, more complete studies comparing their real efficacy and safety are needed urgently. The aim of this study was to investigate and describe practical considerations of a porcine model that can be used to assess such prophylactic agents. First, 10 healthy 5½ months old female pigs (24.3–31.3 Kg) underwent a standardized laparoscopy to provoke peritubal adhesion formation without prophylactic agents. After 30 days, a second-look laparoscopy was performed to evaluate adhesions and perform adnexectomy for histopathological evaluation. Adhesions at different sites were classified by grade, for which the scores range from 0 (no adhesion) to 3 (very strong vascularized adhesions), and also by area, with scores ranging from 0 (no adhesion) to 4 (>75% of the injured area). The histopathological evaluation of the distal uterine horns, oviducts and ovaries were compared withthose from a control group of six healthy pigs with no previous surgery. Biological samples were collected to assess vitality, inflammation and renal, hepatic and hematopoietic systems. There were small (but significant) changes in serum albumin (P = 0.07), globulin (P = 0.07), C-reactive protein (P = 0.011), fibrinogen (P = 0.023) and bilirubin (P<0.01) after 30 days, but all values were within the normal range. No inflammation or abscess formation was observed, but different degrees of adhesion were identified. The estimated occurrence of adhesion (scores >0) and of strong / very strong adhesion (scores >1) was 75% (95% CI: 55–94.9) and 65% (95% CI: 45–85), respectively. The porcine model represents a useful animal platform that can be used to test the efficacy and safety of candidate prophylactic agents intended to prevent postoperative peritubal adhesions formation. We present several practical considerations and measures that can help to minimize animal suffering and avoid problems during such experiments.

Boric acid is as effective as hyaluronic acid-based agent in preventing intra-abdominal adhesions in a rat model.

In this experimental rat model, we aimed to investigate boric acid's possible protective effect against the formation of post-operative abdominal adhesions through its anti-inflammatory and antioxidant properties. Forty healthy male albino rats were randomly and evenly allocated to vehicle, hyaluronic acid-based (HA-b) material, boric acid 50 (BA50), boric acid 100 (BA100), and sham groups. Intra-abdominal adhesions were induced by mechanical cecal abrasion. Macroscopic and pathologic assessments of the adhesions were done and tissue tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) levels were measured. Total abdominal adhesion scores were 129.7, 91.07, 53.77, 90.07, and 140.5 for the vehicle, HA-b, BA50, BA100, and sham groups, respectively, with the highest score indicating more severe adhesions. A significant difference in fibrosis scores was noted between both BA50 and BA100, and the sham group (p=0.018). When objective parameters were analyzed, TNF-α levels were significantly lower in the BA50 group than the sham, BA100, and vehicle groups (p=0.01, 0.019, and 0.03, respectively). TGF-β1 levels were also significantly lower in BA50 group than the sham, BA100, and the vehicle groups (p=0.013, 0.016, and 0.05, respectively). No difference was observed for any parameter between BA50 group and HA-b group. Topical boric acid at a dose of 50 mg/kg is found safe and as effective as the hyaluronic acid-based agent in preventing postoperative abdominal adhesions in our rat model.

Anti-interleukin-6 receptor antibody treatment ameliorates postoperative adhesion formation

Postoperative adhesion formation often ruins the quality of life or is an obstacle to illnesses with curative operation such as cancer. Previously we demonstrated that interferon-γ-promoted fibrin deposition drove postoperative adhesion formation. However, its underlying cellular and molecular mechanisms remain poorly understood. We found that myofibroblasts of the adhesion predominantly expressed signature molecules of mesothelial cells that line the serosa. Microarray analysis revealed IL-6 as a key underlying player, supported by elevated IL-6 levels in the peritoneal fluid of post-laparotomy human subjects. Injured serosa of cecum-cauterized mice also exhibited induction of Il6, which was followed by Tnf, concomitant with rapid accumulation of neutrophils, substantial population of which expressed TGF-β1, a master regulator of fibrosis. Besides, neutrophil-ablated mice showed reduction in induction of the adhesion, suggesting that TGF-β1+neutrophils triggered the adhesion. Human neutrophils expressed TGFB1 in response to TNF-α and TNF in response to IL-6. Moreover, anti-IL-6 receptor monoclonal antibody abrogated neutrophil recruitment and adhesion formation. Thus, IL-6 signaling represents a potential target for the prevention of postoperative adhesions.

NPPB prevents postoperative peritoneal adhesion formation by blocking volume-activated Cl- current.

5-Nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) is a non-specific chloride channel blocker. Peritoneal adhesion is an inevitable complication of abdominal surgery and remains an important clinical problem, leading to chronic pain, intestinal obstruction, and female infertility. The aim of this study is to observe the effects of NPPB on peritoneal adhesions and uncover the underlying mechanism. The formation of postoperative peritoneal adhesions was induced by mechanical injury to the peritoneum of rats. MTT assay and wound-healing assay were used to evaluate proliferation and migration of primary cultured adhesion fibroblasts (AFB) respectively. Whole-cell chloride currents were measured using a fully automated patch-clamp workstation. Cell volume changes were monitored by light microscopy and video imaging. Our results demonstrated that NPPB could significantly prevent the formation of peritoneal adhesion in rats and inhibit the proliferation of AFB in a concentration-dependent manner. NPPB also reduced the migration of AFB cells with an IC50 of 53.09 μM. A 47% hypotonic solution successfully activated the ICl,vol in AFB cells. The current could be blocked by extracellular treatment with NPPB. Moreover, 100 μM NPPB almost completely eliminated the capacity of regulatory volume decrease (RVD) in these cells. These data indicate that NPPB could prevent the formation of postoperative peritoneal adhesions. The possible mechanism may be through the inhibition of the proliferation and migration of AFB cells by modulating ICl,vol and cell volume. These results suggest a potential clinical use of NPPB for preventing the formation of peritoneal adhesions.

Peritoneal regeneration and pathogenesis of postoperative peritoneal adhesions formation

Despite the long history of the peritoneal regeneration and the peritoneal adhesions formation pathogenesis studies, as well as a large number of clinical and experimental trials, so far, many questions about the pathophysiology of postoperative adhesions remain controversial. Postoperative formation of peritoneal adhesions is considered to be part of a pathological regeneration process that occurs after any peritoneum injury, especially in connection with surgery. Factors that lead to formation of adhesions are different (mechanical, physical, chemical, infectious, implantation). Inflammatory mediators, free radical oxidation processes, and oxidative stress also play an important role in the modulation of adhesions. A key role in the formation of adhesions belongs to pathological decrease in peritoneal fibrinolytic activity in response to inflammation and surgery. Studies on both animal models and humans have shown that two major factors lead to a decrease in fibrinolysis: a decrease in local tPA activity and an increase in PAI‑1 activity locally and systemically. It is the balance between the activity of tPA and PAI‑1 that plays a central role in the pathological adhesion formation, and the imbalance correlates with the severity of the adhesive process. Thus, pathological adhesion is a multifactorial condition, the development of which is due to a combination of various factors, many of which are genetically determined by local and systemic reactions of the body, and features of surgical treatment. To develop effective methods for prevention and treatment of adhesions, a more complete understanding of this process is needed at both the cellular and molecular genetic levels. The key to preventing post‑operative adhesion formation is likely to be the selective suppression of one or more critical factors that are necessary for its formation. There are practically no works in literature to study the features of adhesions pathogenesis in children.

Current controversies in tubal disease, endometriosis, and pelvic adhesion

Reproductive surgery for proximal and distal tubal occlusion, as well as for reversal of tubal ligation, may be an alternative or an adjunct to IVF. Surgery for adenomyosis and endometriosis, including endometriomas, may be considered for the treatment of infertility and/or pelvic pain but carries the risks of surgical complications and diminished ovarian reserve. A greater understanding of the pathogenesis of postoperative peritoneal adhesion formation is needed to develop more effective preventive measures to optimize the clinical results of surgery.

Danhong Injection Alleviates Postoperative Intra-abdominal Adhesion in a Rat Model.

Background Among all the common complications that occur after abdominal surgery, intestinal adhesion is perhaps the most unpleasant one. However, current methods to treat and prevent intestinal adhesion are limited; thus, exploring new methods to prevent and treat intestinal adhesion is greatly needed. In this study, we demonstrated that Danhong injection (DHI) may be used as a promising method to prevent and treat intra-abdominal adhesion in a rat model. Materials and Methods Forty-eight rats were randomly divided into six groups. Except for the sham-operated group, all rats underwent cecal abrasion to establish an adhesion model. After the operation, the rats in the DHI-treated groups received different doses of DHI via the tail vein daily, while the other group was treated with the same volume of saline solution. Seven days after the operation, all rats were sacrificed, and the degree of adhesion was evaluated by Nair's scoring system. The extent of inflammation in the adhesion tissue was detected by HE staining and the expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β). The collagen deposition was assessed by Sirius red staining and α-SMA, MMP9, t-PA, and PAI-1 levels. Oxidative stress was indicated by the level of reactive oxygen species (ROS) in adhesion tissues and by immunohistochemical labeling of Nrf2. Furthermore, rat primary peritoneal mesothelial cells (RPMCs) were treated with H2O2 and DHI, and NF-κB phosphorylation was detected to illustrate the effect of DHI on oxidative stress. Results The intra-abdominal adhesion scores were significantly decreased in the groups treated with a high dose of DHI compared with the control groups, and the degree of inflammation, fibrosis, and oxidative stress was also significantly decreased. DHI treatment significantly reduced the levels of TNF-α, TGF-β1, and PAI and increased the expression levels of MMP9, Nrf2, and t-PA in the adhesion tissues. ROS levels and NF-κB phosphorylation were significantly reduced in DHI-treated RPMCs compared with the control RPMCs. Conclusion DHI alleviates the formation of postoperative intra-abdominal adhesions by inhibiting inflammation, collagen deposition, and oxidative stress in a rat model and may serve as a promising drug to prevent intra-abdominal adhesions.