Standardised pomegranate peel extract lavage prevents postoperative peritoneal adhesion by regulating TGF-ß and VEGF levels.

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.

Preventive effect of Rumex crispus L. on surgically induced intra-abdominal adhesion model in rats.

BACKGROUND: Rumex crispus L. (Polygonaceae), known as "Labada" in Turkey, was reported to be used for the treatment of gynecological diseases such as postpartum complications and infertility in folk medicine. Earlier studies on R. crispus have shown that leaf, fruit and root extracts have anti-inflammatory and antioxidant activities and are used for the treatment of tumors in the uterus. The hypothesis of this study is that R. crispus may generate potential anti-adhesive activity against complex factors such as inflammation, oxidation and fibrosis. OBJECTIVES: We aimed to investigate the potential anti-adhesive activity of aqueous methanol extracts of leaves, fruits and roots of R. crispus. METHODS: Abdominal adhesion model was performed in 72 female Wistar Albino rats. In the first step of the experiment, the rats were divided into six groups namely, Sham, Control, Reference and Experimental Groups (consisting of three sub-groups in which R. crispus leaf, fruit and root extracts were applied at 100 mg/kg dose). The test samples were administered once to the peritoneal cavity and the rats were sacrificied at the end of the 14th day. Root extract showed prominent activity, therefore this extract was subjected to fractionation to obtain 3 fractions (30-60-100% methanol fractions) by using vacuum-liquid chromatography. In the second stage, animals were divided into 6 groups as Sham, Control, Reference and Experimental Groups (R30, R60, R100 at 100 mg/kg dose). Adhesion scoring, tissue total antioxidant and oxidant levels, histopathological and immunohistochemical (TNF-α, IL-6 and IL-8) analyzes were performed. RESULTS AND CONCLUSION: Adhesion scores, inflammatory cytokines and inflammation cells decreased by the application of R. crispus root extract. The fractions also showed similar anti-inflammatory effects, but R60 was found to be more effective in prevention of intra-abdominal adhesions and uterine fibrosis. R60 fraction, possessing potential bioactivity, was investigated in terms of phenolic composition by HPLC.

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-ß (TGF-ß). 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-ß1, 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.

Mechanical properties of the pectin hydrogels and inflammation response to their subcutaneous implantation.

We studied the influence of the mechanical properties of pectin hydrogels on acute inflammation and tissue repair after subcutaneous implantation. We used hard and soft pectin hydrogels. The results of histology and the analysis of serum-level cytokines demonstrated that the intensity of acute inflammation increased with increasing hardness of the pectin hydrogels. We also showed that the pectin hydrogels did not inhibit tissue repair. The results of the morphometric and texture analysis of the pectin hydrogels showed that the in vivo biodegradation kinetics of hard hydrogels were greater than those of soft pectin hydrogels. We also observed that on the surface of the hard and soft pectin hydrogels, a network of collagen fibers was formed. The surface of the pectin hydrogel was shown to prevent the adhesion of infiltrating inflammatory cells. The results of the in vitro experiments demonstrated that pectin hydrogels inhibited the functional activity of macrophages and minimally activated the complement system. Therefore, we showed that soft pectin hydrogels have low proinflammatory potential and can be used in surgery as a barrier material as prevention of adhesions in the abdominal cavity. The hard pectin hydrogel can be used in tissue engineering. The hard pectin hydrogels can be used in the reconstruction of skin because are overpopulated with collagen fibers and contribute to the formation of new connective tissue, their elasticity is comparable to the skin and can be adjusted. They are biodegradable, and no additional manipulation is required to remove them.

Developmental endothelial locus-1 prevents development of peritoneal adhesions in mice.

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.

Thermal Preconditioning May Prevent Tendon Adhesion by Up-Regulating HSP72 in Rats.

BACKGROUND/AIMS: The study aims to determine the effects of thermal preconditioning on tendon adhesion by regulating the expression of heat shock protein 72 (HSP72) in rat models. METHODS: Sixty male Wistar rats were collected and randomly assigned into the thermal preconditioning and control groups. During the 4th and 8th weeks following surgery, 15 rats were sacrificed in each period respectively, and their tendon adhesion was observed and evaluated. Biomechanical testing was performed to measure the tensile strength and gliding distance of tendons. Hematoxylin-eosin (HE) was used to observe the morphological structure of the tendons. Immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the HSP72, fibroblast growth factor-2 (FGF-2), fibroblast growth factor receptor-1 (FGFR-1), ß-catenin, epithelial cell adhesion molecule (EPCAM), Tenomodulin and scleraxis protein expressions. Pearson correlation analysis was applied to analyze the correlation between HSP72 expression and tendon adhesion. RESULTS: At the 4th week after surgery, we found no differences in the tendon adhesion scores or mRNA and protein expressions of HSP72 between the thermal preconditioning and control groups. However, after the 8th week after surgery, the thermal preconditioning group had a lower tendon adhesion score and higher mRNA and protein expressions of HSP72 than the control group. During the same period, we found longer gliding distance and higher expression levels of FGF-2, FGFR-1, ß-catenin, Tenomodulin and scleraxis, but lower EPCAM expression in the thermal preconditioning group. Pearson correlation analysis indicated that HSP72 mRNA and protein expression levels were negatively correlated with tendon adhesion. CONCLUSIONS: These findings provide evidence that thermal preconditioning may alleviate tendon adhesions via upregulation of HSP72 expression.

REDUCTION OF INTRA-ARTICULAR ADHESION BY TOPICAL APPLICATION OF DAIDZEIN FOLLOWING KNEE SURGERY IN RABBITS.

BACKGROUND: Intra-articular adhesion is the commonest complication that is faced by orthopedic surgeons after knee surgery. Thus, the present investigation evaluates the effect of daidzein on intra-articular adhesion in rabbits. MATERIAL AND METHODS: All the rabbits were separated in to four different groups each group carries ten rabbits. Cancellous bone was exposed in each rabbit by removing cortical bone from both side of the femoral condyle. Following daidzein (2.5, 5 and 10 mg/ml) was topically applied for the duration of 10 min to the decorticated areas. Thereafter for the period of 4 week surgical limb was fixed. Effect of daidzein on intra articular adhesion was estimated by visual score through macroscopic examination, histopathology study, hydroxyproline content, fibroblast and collage density. RESULTS: Data obtained in the study suggest that topical application of daidzein (5 and 10 mg/ml) loose the collagen and significantly decreases the adhesion at the decorticated areas. Moreover there were significant reduction in the fibroblast density, hydroxyproline content and optical density of collagen tissue in daidzein (5 and 10 mg/ml) treated group than control. CONCLUSION: Thus present study concludes that topical application of daidzein reduces intra-articular adhesion around the knee.

Comparison of honey and dextrose solution on post-operative peritoneal adhesion in rat model.

BACKGROUND: Peritoneal adhesion between abdominal organs is a complication of surgery. It causes major complications like pain, bowel obstruction, infertility and increases risk of death. Honey is known to have anti-inflammatory and antioxidant properties potentially relevant for adhesive protection. METHODS: Thirty rats were divided into five groups: negative control without any surgical procedure (normal group), control group treated with normal saline, experimental group I treated with 1ml of 10% honey, experimental group II treated with honey at half concentration of group I (honey0.5), and positive control group receiving 1ml of dextrose 5%. Inflammatory, growth and angiogenesis factors (TNF-α, Il-6, IL-1ß, TGF-ß1 and VEGF) of the adhesion tissue were assessed using ELISA. Antioxidant factors (NO, GSH and MDA) were also assessed using biochemical procedures. RESULTS: The difference between peritoneal adhesion scores, TNF-α, IL-1ß, IL-6, TGF-ß1, VEGF, NO, GSH and MDA value of all groups was strongly significant (p<0.001). We showed that honey can decrease peritoneal adhesion (p<0.001), TNF-α (p<0.001), IL-1ß (p<0.001), IL-6 (p<0.001), TGF-ß1 (p<0.001), VEGF (p<0.001), NO (p<0.001), MDA (p<0.001) and increase GSH (p<0.001) compared with control group. Honey 0.5 also significantly decreased peritoneal adhesion (p<0.001), TNF-α (p<0.001), IL-1ß (p<0.01), IL-6 (p<0.001), VEGF (p<0.001), NO (p<0.001), MDA (p<0.01) and increase GSH (p<0.001) compared with control group. CONCLUSIONS: We find that honey can decrease inflammatory, growth and angiogenesis factors which can advance peritoneal adhesion and increase antioxidant factors. Honey could serve as a protective agent for peritoneal adhesion.

Hemostasis vs. epidural fibrosis?: A comparative study on an experimental rat model of laminectomy.

AIM: The aim of this study was to evaluate the histopathological and biochemical impact and effectiveness of two hemostatic agents, Ankaferd blood stopper (ABS) and Microporous Polysaccharide Hemospheres (MPH), on epidural fibrosis in an experimental rat laminectomy model. MATERIAL AND METHODS: Twenty adult Wistar albino rats were divided into MPH-treated (n=6), ABS-treated (n=6) and control (n=8) groups. Laminectomy of the lumbar spine was performed in all animals and treatment groups were exposed to MPH and ABS while closure was applied in control group as per usual. Epidural fibrosis was evaluated in all groups macroscopically, histopathologically, biochemically and with electron microscopy four weeks later. RESULTS: Statistically, it was found that MPH-treated group had significantly less epidural fibrosis compared to ABS-treated and control groups. CONCLUSION: We compared two hemostatic agents for their propensity to cause adhesions in the present study. Our results show that MPH significantly reduces epidural scar formation and dural adhesion in a rat model of laminectomy while ABS increases postoperative fibrosis.

Reduction of intraarticular adhesion of knee by local application of rapamycin in rabbits via inhibition of fibroblast proliferation and collagen synthesis.

BACKGROUND: The formation of intraarticular adhesion is a common complication after total knee arthroplasty or anterior cruciate ligament reconstruction. Previously, little research was reported regarding whether the local application of rapamycin (RAPA) could reduce intraarticular adhesion following knee surgery. In our present study, we determined the therapeutic effect of RAPA by local application on the reduction of intraarticular adhesion following knee surgery in rabbits. METHODS: In this study, we built the model of knee surgery according to a previous study. The decorticated areas of the cortical bone were exposed and covered with cotton pads soaked with different concentrations of RAPA or physiological saline for 10 min. All of the rabbits were euthanized 4 weeks after the surgery. Macroscopic evaluation of the hydroxyproline content, the histological morphological analysis and collagen density and fibroblast density were used to evaluate the effect of RAPA on reducing intraarticular adhesion. RESULTS: The results shown that RAPA could significantly inhibit the proliferation of fibroblasts and reduce collagen synthesis; in the rabbit model of knee surgery, there were weak scar tissues around the decorticated areas in the 0.2 mg/ml RAPA group; moderate scar tissues were found in the 0.1 mg/ml RAPA group. However, severe fibrous adhesions were found in the 0.05 mg/ml RAPA group and the control group. The hydroxyproline content and the fibroblast density in the 0.2 mg/ml and 0.1 mg/ml RAPA groups were significantly less than those of the control group. CONCLUSIONS: We concluded that the local application of RAPA could reduce intraarticular adhesion after knee surgery in the rabbit model; this effect was mediated by inhibition of fibroblast proliferation and collagen synthesis, which may provide a new method for reducing intraarticular adhesion after clinical knee surgery.

Intraperitoneal administration of activated protein C prevents postsurgical adhesion band formation.

Postsurgical peritoneal adhesion bands are the most important causes of intestinal obstruction, pelvic pain, and female infertility. In this study, we used a mouse model of adhesion and compared the protective effect of activated protein C (APC) to that of the Food and Drug Administration-approved antiadhesion agent, sodium hyaluronate/carboxymethylcellulose (Seprafilm) by intraperitoneal administration of either APC or Seprafilm to experimental animals. Pathological adhesion bands were graded on day 7, and peritoneal fluid concentrations of tissue plasminogen activator (tPA), d-dimer, thrombin-antithrombin complex, and cytokines (IL-1ß, IL-6, interferon-γ, tumor necrosis factor-α, transforming growth factor-ß1) were evaluated. Inflammation scores were also measured based on histologic data obtained from peritoneal tissues. Relative to Seprafilm, intraperitoneal administration of human APC led to significantly higher reduction of postsurgical adhesion bands. Moreover, a markedly lower inflammation score was obtained in the adhesive tissues of the APC-treated group, which correlated with significantly reduced peritoneal concentrations of proinflammatory cytokines and an elevated tPA level. Further studies using variants of human APC with or without protease-activated receptor 1 (PAR1) signaling function and mutant mice deficient for either endothelial protein C receptor (EPCR) or PAR1 revealed that the EPCR-dependent signaling activity of APC is primarily responsible for its protective activity in this model. These results suggest APC has therapeutic potential for preventing postsurgical adhesion bands.

Prevention of experimental postoperative peritoneal adhesions through the intraperitoneal administration of tanshinone IIA.

Postoperative adhesions develop after nearly every abdominal surgery. The formation of adhesions is associated with the inflammatory response, fibrinolytic system, and extracellular matrix deposition in response to injury. Tanshinone IIA is one of the major extracts obtained from Salvia miltiorrhiza, which has anti-inflammatory effects on many diseases. Postoperative adhesions were induced by injuring the parietal peritoneum and cecum in Wistar rats, followed by the administration of various dosages of tanshinone IIA. The adhesion scores for each group were collected seven days after the initial laparotomy. The activity of the tissue-type plasminogen activator in the peritoneal lavage fluid was measured. The messenger ribonucleic acid expression levels of the tissue-type plasminogen activator, plasminogen activator inhibitor-1, and cyclooxygenase-2 in the ischaemic tissues were measured by quantitative real-time polymerase chain reaction. The intraperitoneal administration of tanshinone IIA is effective for the prevention of the formation of postoperative adhesions in rats. Tanshinone IIA increased fibrinolytic activity in the peritoneal lavage fluid and tissue-type plasminogen activator messenger ribonucleic acid expression in ischaemic peritoneal tissues but decreased the plasminogen activator inhibitor and cyclooxygenase-2 messenger ribonucleic acid expression significantly. These results revealed that tanshinone IIA was a potent postoperative adhesion preventer by enhancing fibrinolytic activity and decreasing cyclooxygenase-2 activity.

Intraperitoneal Nigella sativa for prevention of postoperative intra-abdominal adhesions in rats.

OBJECTIVE: To evaluate intraperitoneal administration of Nigella sativa (NS) to prevent postoperative intraperitoneal adhesion (PPA) after surgical manipulation of rat uterine horn. MATERIALS AND METHODS: Two forms of NS were used in the study (Volatile oil (NSVO) and the ethanolic extract (NSEE)). A total of 50 rats were randomly assigned to the sham group (n = 10), control group (n = 10), NSVO group (n = 10), NSEE group (n = 10), and the Seprafilm group(n = 10). After 14 days, rats were sacrificed. Adhesions were examined macroscopically, and degree of adhesions was scored. A part of horn was excised, and superoxide dismutase (SOD) and glutathione peroxidase activities as well as malondialdehyde levels were evaluated, and histological score was calculated. RESULTS: Total microscopic score of the NSEE group was significantly lower than the control group (p = .001) and was marginally significantly lower than the seprafilm group (p = .005). Collagen formation score was higher in the seprafilm group compared to the sham and NSEE groups (p < 0.001, p = .003, respectively). Apoptotic cells were lower in the NSEE group compared to the control group (p = .003) and also lower in the NSEE and NSVO groups compared to the seprafilm group (p = .001, p < .001, respectively). Only SOD activity was higher in the NSVO and seprafilm groups compared to the control group (p < .001). CONCLUSION: NSEE form seems to have a possible effect in the prevention of PPAs. This may occur by its effect in decreasing collagen formation and by decreasing apoptosis in the injured tissues. NSVO form seems to induce SOD. Therefore, combined use of NSVO with seprafilm may increase the adhesion preventive effect of seprafilm.

Berberine hydrochloride prevents postsurgery intestinal adhesion and inflammation in rats.

Intestinal adhesion, characterized by connection of the loops of the intestine with other abdominal organs by fibrous tissue bands, remains an inevitable event of abdominal operations and can cause a number of complications. Berberine hydrochloride (berberine), a natural plant alkaloid derived from Chinese herbal medicine, is characterized by diverse pharmacological effects, such as anticancer and lower elevated blood glucose. This study is designed to investigate the effects of berberine on adhesion and inflammation after abdominal surgeries and the underlying molecular mechanisms. Adhesion severity grades and collagen deposition were assessed 14 days after surgery. We evaluated the levels of intercellular adhesion molecule-1 (ICAM-1) and inflammatory cytokines interleukin-1ß (IL-1ß), IL-6, transforming growth factor ß (TGF-ß), tumor necrosis factor-α (TNF-α), and examined transforming growth factor-activated kinase 1 (TAK1)/c-Jun N-terminal kinase (JNK) and TAK1/nuclear factor κB (NF-κB) signaling. The surgery group experienced the most severe adhesions, and berberine strikingly reduced the density and severity of adhesion. Results showed significant lower expression of IL-1ß, IL-6, TGF-ß, TNF-α, and ICAM-1, in berberine groups compared with the operation group. Activities of phosphorylated JNK and phosphorylated NF-κB were inhibited in the berberine groups compared with the surgery group. Our novel findings identified berberine hydrochloride as a promising strategy to prevent adhesion by downregulating ICAM-1 and reduce inflammation by inhibiting the TAK1/JNK and TAK1/NF-κB signaling after abdominal surgery, which brought out a good therapeutic approach for the development of clinical application for postoperative abdominal adhesion and inflammation.

[Effects of Fukang oral liquid on the prevention of intrauterine adhesion and expressions of TGF-beta1, PAI-1 and MMP-9 in endometrium of rats].

OBJECTIVE: To investigate the preventing effect of Fukang oral liquid (fuk) in intrauterine adhesions and its effects on the expression of TGFbeta-1, PAI-1 and MMP-9 in endometrium of rats with intrauterine adhesions. METHODS: 50 female wistar rats were divided into high, medium, low dose of Fukang oral liquid group (Hfuk, Mfuk, Lfuk), blank control group (Bcon), and model control group (Mcon) (n = 10 in each group). The rats in Hfuk, Mfuk and Lfuk groups were treated with intragastric administration of 4 mL, 2 mL and 1 mL Fukang Oral Liquid per day, while the rats in Mcon group and Bcon group received 2 mL physiological saline intragastric administration per day. All of rats were executed on 10th day and the sample of endometrium was harvested for the study of histology and morphology and the expression of TGFbeta-1, PAI-1 and MMP-9. RESULTS: Under the light microscope, the organizational structure of the uterine cavity and uterine wall was clear in Bcon group, the uterine cavity disappeared in Mcon group, and the layers structure remained normal arrangement in three fuk treated groups. TGFbeta-1 and PAI-1 protein expressions in Hfuk, Mfuk, Lfuk groups were less than those in Mcon group (P < 0.001), but MMP-9 protein expressions were higher. (P < 0.001). CONCLUSION: Fukang oral liquid show preventing effect on IUA, the mechanism may be related to its effects on the expressions of TGF-beta1, PAI-1, and MMP-9 in the endometrium.

Medical ozone therapy decreases postoperative uterine adhesion formation in rats.

PURPOSE: Various studies have been performed to find out novel treatment strategies to prevent postoperative adhesion formation. Ozone therapy (OT) is shown to reduce inflammation in several pathological conditions. Therefore, we aimed to evaluate the efficacy of OT in a rat model of experimental uterine adhesion (EUA). METHODS: Thirty female Wistar rats (200-250 g) were divided into three groups: sham, EUA and EUA+OT. EUA and EUA+OT groups were subjected to the postoperative adhesion procedure by bipolar coagulation on the uterine horns and corresponding pelvic sidewall parietal peritoneum. EUA+OT group received 0.7 mg/kg daily single dose for 3 days of ozone/oxygen mixture intraperitoneally after adhesion induction. All animals were killed on the 7th day and uterine adhesions were scored. Uterine tissues and peritoneal washing fluid were harvested for all analyses. RESULTS: Uterine malondialdehyde levels in the EUA group were significantly higher compared to the other groups. However, in the EUA group, uterine superoxide dismutase and glutathione peroxidase activities were lower than in other groups. Peritoneal fluid TNF-α levels were found to be significantly different for all groups (p < 0.001). Macroscopic total adhesion score was significantly higher in the EUA group compared to the other groups (p < 0.001). But, total score in the EUA+OT group was lower than in the EUA group (p = 0.006). CONCLUSIONS: Medical OT prevents postoperative uterine adhesions by modulating TNF-α levels and oxidative/antioxidative status in an experimental uterine adhesion model.

Synergistic effects of hyperbaric oxygen and granulocytecolony stimulating factor on postoperative adhesion formation in a rat cecal abrasion model.

PURPOSE: We investigated the synergistic effect of hyperbaric oxygen (HBO) and granulocyte-colony stimulating factor (G-CSF) on adhesion formation in rats. METHODS: 40 adult male Sprague-Dawley rats (250-350 g) were divided into 4 groups. In group-1, no further management was undertaken. Group-2 received HBO therapy, group-3 was treated with 50 ug/kg subcutaneous G-CSF once daily for 7 days following laparatomy and cecal abrasion and group-4 was given both G-CSF and HBO therapies. On the 7th day, all rats were sacrificed and adhesions were scored. Tissue samples from adhesions and peritonea and cecum wall were examined both pathologically and biochemically for tissue hydroxyproline content. RESULTS: No mortality occurred in study groups. When the groups were evaluated according to the adhesion numbers and grades, there was a statistically significant difference between the control and groups 3 and 4 (P < 0.001). There was no statistically significant difference between groups 1 and 2 (p > 0.05). HBO + G-CSF group was significantly different from control, HBO and G-CSF groups, regarding hydroxyproline contents (p = 0.005). Inflammation and fibrosis did not differ significantly among the groups (p = 0.248), (p = 0.213). CONCLUSION: HBO treatment could not reduce the adhesion formation alone. Combined use of HBO and G-CSF, has a markedly preventive effect on postoperative adhesion formation (Tab. 1, Fig. 2, Ref. 57).

Tranilast: a pharmaceutical candidate for reduction of adhesions using a novel approach.

Postsurgical adhesion formation has numerous deleterious side effects in a wide variety of surgical settings. Physical barriers used together with laparoscopy were developed in hopes of reducing the tissue trauma seen with open procedures and separating tissues during the critical time of healing to reduce adhesion formation. Despite meticulous techniques by surgeons and the availability of barriers, adhesion formation remains a serious problem, with more than $1 billion spent annually on complications arising from adhesions. Our laboratories have combined a previously marketed drug, Tranilast, with a gel to provide a locally delivered medicated device that can reduce adhesion formation. This article will review the role of Tranilast in the key pathways involved in adhesion formation.

[Mechanism of salvianolate in preventing postoperative intestinal adhesion in rats].

OBJECTIVE: To observe the effects of salvianolate on rats with postoperative intestinal adhesion and to explore the prevention mechanism. METHODS: Forty SD male rats with intestinal adhesion were randomly divided into four groups: untreated group, low-dose salvianolate-treated group (12 mg/kg), medium-dose salvianolate-treated group (24 mg/kg) and high-dose salvianolate-treated group (48 mg/kg), with another ten SD male rats as normal control. Intraperitoneal injection of glucose was administered to the rats in the normal control group and the untreated group, and intraperitoneal injection of salvianolate was administered to the rats in the low-, medium- and high-dose salvianolate-treated groups. They were all treated for 8 days and once a day. On the eighth day after surgery the blood samples of each group were collected. Grades of intestinal adhesion were ranked by macroscopic observation. The adhesive tissues between viscera and belly wall were taken for pathological observation. The levels of interleukin-1beta (IL-1beta), interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-alpha) were determined by enzyme linked immunosorbent assay. RESULTS: Salvianolate can significantly reduce the extent of postoperative intestinal adhesion, obviously decrease the levels of IL-1beta, TNF-alpha and inhibit the hyperplasy of fibrous connective tissue. However, there was no significant impact on the level of IL-4. CONCLUSION: Salvianolate can reduce the extent of postoperative intestinal adhesion, decrease the expression of IL-1beta and TNF-alpha and inhibit the hyperplasy of fibrous connective tissue. This may be the mechanism of salvianolate in preventing intestinal adhesion.

Chinese medicine compound Changtong oral liquid on postoperative intestinal adhesions.

AIM: The aim of this study was to observe the effect of a Chinese medicine compound Changtong oral liquid (CT) on tissue plasminogen activity (t-PA), plasminogen activator inhibitor (PAI), TGF-beta1 and hydroxyproline (OHP). METHODS: Two sets of animal experiments were performed in the present study. Forty New Zealand rabbits and 48 Sprague-Dawley (SD) rats were assigned randomly to one of the five groups: sham adhesion, adhesion with saline, adhesion with low dosage of the CT, adhesion with middle dosage of the CT and adhesion with high dosage of the CT. t-PA and PAI activity in plasma, OHP and TGF-beta1 expression in adhesion were investigated. Analysis of variance was used to test differences among groups. RESULTS: CT treatment increased plasma t-PA activity in rabbits but decreased TGF-beta1 activity in rats. The data were expressed from low to high dose respectively as follows: t-PA, 46.1+/-8.6 microkat/L, 59.6+/-10.1 microkat/L, 64.0+/-11.5 microkat/L; TGF-beta1 28+/-7.23%, 31+/-3.05%, 30+/-4.04%. There were significant differences compared with saline-treated animals (t-PA 26.4+/-5.1 microkat/L, TGF-beta1 54+/-5.51%). OHP content in cecum of rabbits from middle and high but not low dose of CT lowered significantly as compared with saline-treated rabbits, 0.3641+/-0.1373, 0.3348+/-0.0321, 0.2757+/-0.0497 mg/g vs 0.4183+/-0.0883 mg/g of protein, P>0.05, P<0.05, P<0.05 respectively. The rabbit plasma PAI activity and OHP content in abdominal wall had no difference in all groups. CONCLUSION: CT treatment significantly enhanced t-PA activity in rabbits, but decreased TGF-beta1 content in rats, OHP content in cecum of rabbits, and failed to affect the activity of PAI and OHP content in abdominal wall in rabbits, compared with saline group. The result suggests that CT could effectively prevent adhesions without interfering wound healing.