Photobiomodulation therapy at 632 nm wavelength ameliorates intrauterine adhesion via activation of cAMP/PKA/CREB pathway.

Intrauterine adhesion (IUA), a major cause of uterine infertility, is pathologically characterized by endometrial fibrosis. Current treatments for IUA have poor efficacy with high recurrence rate, and restoring uterine functions is difficult. We aimed to determine the therapeutic efficacy of photobiomodulation (PBM) therapy on IUA and elucidate its underlying mechanisms. A rat IUA model was established via mechanical injury, and PBM was applied intrauterinely. The uterine structure and function were evaluated using ultrasonography, histology, and fertility tests. PBM therapy induced a thicker, more intact, and less fibrotic endometrium. PBM also partly recovered endometrial receptivity and fertility in IUA rats. A cellular fibrosis model was then established with human endometrial stromal cells (ESCs) cultured in the presence of TGF-ß1. PBM alleviated TGF-ß1-induced fibrosis and triggered cAMP/PKA/CREB signaling in ESCs. Pretreatment with the inhibitors targeting this pathway weakened PBM's protective efficacy in the IUA rats and ESCs. Therefore, we conclude that PBM improved endometrial fibrosis and fertility via activating cAMP/PKA/CREB signaling in IUA uterus. This study sheds more lights on the efficacy of PBM as a potential treatment for IUA.

Research on Mechanisms of Chinese Medicines in Prevention and Treatment of Postoperative Adhesion.

Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.

Exploring new therapeutic potentials of curcumin against post-surgical adhesion bands.

BACKGROUND: Adhesion band formation is a common cause of morbidity for patients undergoing surgeries. Anti-inflammatory and anti-fibrotic properties of curcumin, a pharmacologically active component of Curcuma longa, have been investigated in several studies. The aim of this study is to explore the therapeutic potential of curcumin in attenuating post-operative adhesion band (PSAB) formation in both peritoneal and peritendinous surgeries in animal models. METHODS: Bio-mechanical, histological and quantitative evaluation of inflammation, and total fibrosis scores were graded and measured in the presence and absence of phytosomal curcumin. RESULTS: Results showed that phytosomal curcumin significantly decreased severity, length, density and tolerance of mobility of peritendinous adhesions as well as incidence and severity of abdominal fibrotic bands post-surgery. Curcumin may decrease inflammation by attenuating recruitment of inflammatory cells and regulating oxidant/anti-oxidant balance in post-operative tissue samples. Moreover, markedly lower fibrosis scores were obtained in the adhesive tissues of phytosomal curcumin-treated groups which correlated with a significant decrease in quantity, quality and grading of fibers, and collagen deposition in animal models. CONCLUSION: These results suggest that protective effects of phytosomal curcumin against PSAB formation is partially mediated by decreasing inflammation and fibrosis at site of surgery. Further studies are needed to investigate the therapeutic potential of this molecule in preventing PSAB.

Evaluation of the Therapeutic Effects of the Hydroethanolic Extract of Portulaca oleracea on Surgical-Induced Peritoneal Adhesion.

OBJECTIVE: Peritoneal adhesion (PA) is an abnormal connective tissue that usually occurs between tissues adjacent to damaged organs during processes such as surgery. In this study, the anti-inflammatory and antioxidant effects of Portulaca oleracea (PO) were investigated against postoperative-induced peritoneal adhesion. METHODS: Thirty healthy male Wistar rats (220 ± 20 g, 6-8 weeks) were randomly divided into four groups: (1) normal, (2) control (induced peritoneal adhesion), and (3) and (4) PO extracts (induced peritoneal adhesion and received 100 or 300 mg/kg/day of PO extract for seven days). Finally, macroscopic and microscopic examinations were performed using different scoring systems and immunoassays in the peritoneal lavage fluid. RESULTS: We found that the levels of adhesion scores and interleukin- (IL-) 1ß, IL-6, IL-10, tumour necrosis factor- (TNF-) α, transforming growth factor- (TGF-) ß 1, vascular endothelial growth factor (VEGF), and malondialdehyde (MDA) were increased in the control group. However, PO extract (100 and 300 mg/kg) notably reduced inflammatory (IL-1ß, IL-6, and TNF-α), fibrosis (TGF-ß 1), angiogenesis (VEGF), and oxidative (MDA) factors, while increased anti-inflammatory cytokine IL-10, antioxidant factor glutathione (GSH), compared to the control group. CONCLUSION: Oral administration of PO improved postoperational-induced PA by alleviating the oxidative factors, fibrosis, inflammatory cytokines, angiogenesis biomarkers, and stimulating antioxidative factors. Hence, PO can be considered a potential herbal medicine to manage postoperative PA. However, further clinical studies are required to approve the effectiveness of PO.

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.

Postoperative peritoneal adhesion: an update on physiopathology and novel traditional herbal and modern medical therapeutics.

Postoperative peritoneal adhesion (PPA) is a serious clinical condition that affects the high percentage of patients after abdominal surgery. In this review, we have tried to focus on pathophysiology and different underlying signal pathways of adhesion formation based on recent progress in the molecular and cellular mechanisms. Also, the strategies, developed based on traditional herbal and modern medicines, to prevent and treat the PPA via regulation of the molecular mechanisms were investigated. The search engines such as Google Scholar, PubMed, Scopus, and Science Direct have been used to evaluate the current literature related to the pathogenesis of adhesion formation and novel products. Recently, different mechanisms have been defined for adhesion formation, mainly categorized in fibrin formation and adhesion fibroblast function, inflammation, and angiogenesis. Therefore, the suppression of these mechanisms via traditional and modern medicine has been suggested in several studies. While different strategies with encouraging findings have been developed, most of the studies showed contradictory results and were performed on animals. The herbal products have been introduced as safe and effective agent which can be considered in future preclinical and clinical studies. Although a wide range of therapeutics based on traditional and modern medicines have been suggested, there is no agreement in the efficacy of these methods to prevent or treat adhesion formation after surgeries. Further basic and clinical researches are still needed to propose the efficiency of recommended strategies for prevention and treatment of PPA.

Therapeutic Role of Water-Soluble Contrast Media in Adhesive Small Bowel Obstruction: a Systematic Review and Meta-Analysis.

BACKGROUND: Adhesive small bowel obstruction (ASBO) is a common post-operative cause of hospitalisation. Water-soluble contrast media (WSCM) has become a popular non-surgical approach to treatment. However, previous reviews have concluded with conflicting results. This meta-analysis of randomised controlled trials (RCTs) re-evaluated the therapeutic value of WSCM in the management of ASBO. METHODS: A comprehensive search of PubMed, Embase, and Cochrane databases was undertaken to identify RCTs from January 2000 to November 2018. The primary outcomes of length of stay and secondary outcomes of time to resolution, need for surgery, and mortality were extracted from the included studies. Quantitative pooling of the data was based on the random effects model. RESULTS: Eight hundred and seventy-nine patients from the nine studies were included in the analysis. The administration of oral WSCM reduced the length of hospital stay (weighted mean difference - 0.15 days, P < 0.0001). However, WSCM does not reduce the need for surgery (relative risk 0.84, P < 0.009) and makes no difference to mortality rate (RR 0.99, P < 1.000). The definition of time to resolution of ASBO differed between the studies, ranging from time to passing flatus, to cessation of abdominal pain, and time to initiating oral intake. The significant differences in definition precluded meaningful quantitative pooling of this outcome. CONCLUSIONS: This meta-analysis evaluating the therapeutic value of WSCM has shown that it does not reduce the need for operative management in ASBO or impact mortality rates. It shortens hospital stay by 0.15 days (3.6 h) which is not clinically significant.

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.

The Effect of Daikenchuto, Japanese Herbal Medicine, on Adhesion Formation Induced by Cecum Cauterization and Cecum Abrasion in Mice.

Daikenchuto (DKT) has been widely used for the treatment of postsurgical ileus in Japan. However, its effect on postsurgical adhesion formation has been obscure. In this study, the effect of DKT on postsurgical adhesion formation induced by cecum cauterization or cecum abrasion in mice was investigated. First, the expression of adhesion-related molecules in damaged ceca was investigated by quantitative (q)RT-PCR. During 24 h after surgery, mRNA expressions of interferon-γ (IFN-γ), plasminogen activator inhibitor-1 (PAI-1), interleukin-17 (IL-17), and Substance P (SP) in cauterized ceca and those of PAI-1 and IL-17 in abraded ceca were significantly up-regulated. Next, the effect of DKT on adhesion formation macroscopically evaluated with adhesion scoring standards. DKT (22.5-67.5 mg/d) was administered orally for 7 d during the perioperative period, and DKT did not reduce adhesion scores in either the cauterization model (control : DKT 67.5 mg/d, 4.8 ± 0.2 : 4.8 ± 0.2) or in the abrasion model (control : DKT 67.5 mg/d, 4.9 ± 0.1 : 4.5 ± 0.3). Histologically, collagen deposition and leukocyte accumulation were found at the adhesion areas of control mice in both models, and DKT supplementation did not alleviate them. Last, effect of DKT on expression of proadhesion moleculs was evaluated. DKT also failed to down-regulate mRNA expression levels of them in damaged ceca of both models. In conclusion, PAI-1 and IL-17 may be key molecules of postsurgical adhesion formation. Collagen deposition and leukocytes accumulation are histological characteristic feature of post-surgical adhesion formation. DKT may not have any preventive effect on postsurgical adhesion formation in mice.

Tetramethylpyrazine Improves Postoperative Tissue Adhesion: A Drug Repurposing.

Plants are known to possess plenty of pharmacological activities as a result of various phytoconstituents. Tetramethylpyrazine (TMP), one of the most widely used medicinal compound isolated from traditional Chinese herb, is usually employed for anti-oxidation, anti-inflammation, anti-platelet aggregation, anti-lipid, anti-fibrosis, as well as activating blood, removing stasis, dilating small arteries, improving microcirculation and antagonizing calcium. In the present paper, the anti-adhesion effect of TMP were reviewed. TMP was found to play a multi-target and muti-link role in anti-adhesion by inhibiting hyperplasia of collagen and overexpression of adhesion-related factors and reducing the concentration of white blood cells and fibrin in plasma. Because previous studies mostly focused on in vitro experiments and animal experiments, there is an urgent need for clinical research with abundant indicators to further prove its anti-adhesion potency. Future basic research should concentrate on the development of TMP as a biological material.

Evaluation of the effects of Iranian propolis on the severity of post operational-induced peritoneal adhesion in rats.

BACKGROUND: Peritoneal adhesion is a major complication of surgery that can lead to serious problems such as bowel obstruction, pain, infertility and even mortality. Propolis is a honey bee product with anti-inflammatory and anti-oxidant activities that could potentially protect against adhesive surgical complications. METHODS: Forty 8-weeks-old rats (275 ±â€¯25 g) were divided into five groups: normal group without any surgical procedure, and experimental groups treated with normal saline, 50 mg/kg, 100 mg/kg and 200 mg/kg of propolis. Peritoneal adhesions were examined macroscopically and also, the levels of inflammatory factors (IL-6, IL-1ß and TNF-α), growth factors (TGF-ß1 and VEGF) were evaluated in the study groups using ELISA. Biochemical indices of oxidative status including Nitric Oxide (NO), Malondialdehyde (MDA) and Glutathione (GSH) were also measured. RESULTS: Peritoneal adhesion scores, IL-1ß, IL-6, TNF-α, TGF-ß1, VEGF, NO, GSH and MDA levels were significantly different between the study groups (p < 0.001). Propolis treatment reduced 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) and MDA (p < 0.001), while GSH levels were increased (p < 0.001) compared with the vehicle group. Our results showed that higher dose of propolis was associated with significantly greater reductions in peritoneal adhesion (p < 0.001), TNF-α (p < 0.001), IL-1ß (p < 0.001), IL-6 (p < 0.001), VEGF (p < 0.001), NO (p < 0.001) and MDA (p < 0.001), a greater increase in GSH levels (p < 0.001) compared with the lower dose. CONCLUSIONS: Propolis treatment can dose-dependently reduce peritoneal adhesion through its anti-inflammatory, anti-angiogenic and antioxidant properties. Therefore, propolis might serve as a protective agent against post-surgical adhesive complications.

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.

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.

[Prevention of abdominal adhesions in rats by rhynchophylline through inhibition of Smad singnaling pathway].

Postoperative intra-abdominal adhesion is one of the most common complications in the postoperative period. Current remedies are very ineffective to prevent the pathological outcomes except steroid hormones. Rhynchophylline is deemed as a pharmacologically active component from traditional Oriental medicine Uncaria rhynchophylla (Miq.) Jacks. (Rubiaceae). This study was designed to investigate the preventative effect of rhynchophylline on the abdominal adhesions in rats. Rhynchophylline relieved the experimental abdominal adhesion and decreased the levels of interleukin-1 ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the blood serum in a dose-dependent manner. The levels of transforming growth factor- ß1 (TGF-ß1) and connective tissue growth factor (CTGF) were reduced significantly in the peritoneal fluid. The potential mechanism of the activity is related to inhibition of the TGF- ß1/Smad signaling pathway.

Preoperative vitamin C supplementation improves colorectal anastomotic healing and biochemical parameters in malnourished rats.

PURPOSES: The objective of this study was to evaluate the effect of supplementation with vitamin C on intestinal anastomosis healing in malnourished rats. METHODS: Male Wistar rats were divided into three groups: (1) sham, well-nourished rats that received vehicle; (2) FR+Veh, rats that were subjected to food restriction and received vehicle; and (3) FR+VC, rats that were subjected to food restriction and received vitamin C. Four days before surgery, the animals received vitamin C (100 mg/kg/day) via gavage and underwent colon resection with anastomosis in a single plane. The survival rate of rats was monitored until day 7 after surgery. Regarding anastomosis tissues, we examined intra-abdominal adhesion index, hydroxyproline content, collagen density, inflammatory parameters, and oxidative damage to proteins and lipids. RESULTS: Malnutrition decreases body weight and increases mortality; the survival rate was 90 % in group 1, 60 % in group 2, and 80 % in group 3. Vitamin C was able to increase hydroxyproline concentration and density of collagen and decrease the intra-abdominal adhesion index, as well as the infiltration of neutrophils and oxidative damage to proteins in malnourished rats compared to group treated with vehicle. CONCLUSIONS: Preoperative vitamin C supplementation can improve the intestinal anastomosis healing, biochemical alterations, and prolong survival in rats subjected to food restriction.

The Effect of Ethanol Extract of Rose (Rosa damascena) on Intra-abdominal Adhesions After Laparotomy in Rats.

BACKGROUND: Abdominal adhesions are pathological connections in peritoneal surfaces that are created after abdominal surgery. The aim of this study was to evaluate the inhibitory effect of Rosa damascena extract on adhesions, considering the antioxidant properties of rose. METHODS: Thirty healthy rats were divided into 3 groups: rats treated by 1% (A) and 5% (B) of R. damascena extract and the con- trol group (C). After administering anesthesia, the abdominal wall was opened and 3 shallow incisions (2 cm) were made on the right wall, and a 2 × 2 piece of peritoneal surface was removed on the left side of the abdominal wall. Then 3 mL of 1% (A) and 5% (B) R. damascena extract was administered into the abdominal cavity. The control group (C) received 3 mL of distilled water. The abdominal cavity was sutured, and a second laparotomy was carried out 14 days later to the created adhesions according to the Canbaz scale, and a histopathologic examination was also performed. All data was analyzed by SPSS volume 16 (Chicago, IL); P less than 0.05 was considered statistically significant. RESULTS: The amount of adhesion in group A was significantly lower than that of group C, 1.4 ± 1.265 versus 3 ± 0.816, (P = 0.007). The histological investigation also showed significant differences in the se- verity of fibrosis (P = 0.029) and inflammation (P = 0.009) between groups A and C; all rats in group B (5%) were found dead. CONCLUSION: This study indicated the use of R. damascena at a 1% level resulted in a remarkable decrease of intra-abdominal adhesions after laparotomy in rats. Further studies are necessary on this extract and its derivatives for treatment of such diseases in the human model.

The time course of resolution of adhesions during fibrinolytic therapy in tetracycline-induced pleural injury in rabbits.

The time required for the effective clearance of pleural adhesions/organization after intrapleural fibrinolytic therapy (IPFT) is unknown. Chest ultrasonography and computed tomography (CT) were used to assess the efficacy of IPFT in a rabbit model of tetracycline-induced pleural injury, treated with single-chain (sc) urokinase plasminogen activators (scuPAs) or tissue PAs (sctPA). IPFT with sctPA (0.145 mg/kg; n = 10) and scuPA (0.5 mg/kg; n = 12) was monitored by serial ultrasonography alone (n = 12) or alongside CT scanning (n = 10). IPFT efficacy was assessed with gross lung injury scores (GLIS) and ultrasonography scores (USS). Pleural fluids withdrawn at 0-240 min and 24 h after IPFT were assayed for PA and fibrinolytic activities, α-macroglobulin/fibrinolysin complexes, and active PA inhibitor 1 (PAI-1). scuPA and sctPA generated comparable steady-state fibrinolytic activities by 20 min. PA activity in the scuPA group decreased slower than the sctPA group (kobs = 0.016 and 0.042 min(-1)). Significant amounts of bioactive uPA/α-macroglobulin (but not tPA; P < 0.05) complexes accumulated at 0-40 min after IPFT. Despite the differences in intrapleural processing, IPFT with either fibrinolysin was effective (GLIS ≤ 10) in animals imaged with ultrasonography only. USS correlated well with postmortem GLIS (r(2) = 0.85) and confirmed relatively slow intrapleural fibrinolysis after IPFT, which coincided with effective clearance of adhesions/organization at 4-8 h. CT scanning was associated with less effective (GLIS > 10) IPFT and higher levels of active PAI-1 at 24 h following therapy. We concluded that intrapleural fibrinolysis in tetracycline-induced pleural injury in rabbits is relatively slow (4-8 h). In CT-scanned animals, elevated PAI-1 activity (possibly radiation induced) reduced the efficacy of IPFT, buttressing the major impact of active PAI-1 on IPFT outcomes.

Gelatin sealing sheet for arterial hemostasis and anti-adhesion in vascular surgery: a dog model study.

BACKGROUND: The bilayer gelatin sealing sheet was developed as a safe, effective, easy-to-handle and low-cost hemostatic agent. OBJECTIVE: To examine the feasibility of gelatin sealing sheets using a canine arterial hemorrhage model. METHODS: In vivo degradation of gelatin sealing sheets was examined by implanting subcutaneously in rats. For the hemostatic and anti-adhesion efficacy investigations, femoral arteries of dogs were pricked with syringe needle to make a small hole and a gelatin (i.e. experimental group) or fibrin glue sealing sheet (i.e. control group) was applied on the hole to stop bleeding (n=8). After discontinuation of the bleeding, the skin incisions were closed and re-examined 4 weeks postoperatively. RESULTS: From the degradation study, 4 h thermally treated gelatin sheet which degraded within 3 weeks in vivo was chosen for the further hemostatic study. In all cases of gelatin and fibrin glue sealing sheets, bleeding from the needle hole on canine femoral arteries was effectively stopped. Postoperative adhesions and inflammation at the site in the experimental group were significantly less than those in the control group (P<0.01 for adhesion scores). CONCLUSIONS: The gelatin sealing sheet was found to be as effective as the fibrin glue sealing sheet as a surgical hemostatic agent, and more effective in preventing postoperative adhesions.

SAFETY PROFILE OF OCRIPLASMIN FOR SYMPTOMATIC VITREOMACULAR ADHESION: A Comprehensive Analysis of Premarketing and Postmarketing Experiences.

PURPOSE: After the recent approval of ocriplasmin by the Food and Drug Administration, postmarketing safety concerns have been raised by the vitreoretinal community. The American Society of Retina Specialists Therapeutic Surveillance Committee was commissioned to monitor postmarketing drug-related and device-related adverse events. The purpose of this report is to analyze the postmarketing safety experience in the context of available premarketing safety data. METHODS: Periodic aggregate safety reports consisting of premarketing, or clinical trial, data (n = 999 injections) and postmarketing reports through July 16, 2013 (n = 4,387 injections), were retrospectively analyzed by the TSC. The aggregate data were analyzed to classify adverse events, and the postmarketing safety data for each event type were compared with the premarketing data. RESULTS: Eight categories of adverse events were identified. Acute reduction in visual acuity attributable to either worsening of macular pathology or development of subretinal fluid, electroretinogram changes, dyschromatopsia, retinal tears and detachments, lens subluxation or phacodonesis, impaired pupillary reflex, and retinal vessel findings were reported in both the premarketing and postmarketing experiences. Ellipsoid zone (inner segment/outer segment) findings were only reported in the postmarketing experience. Rates of postmarketing reports were lower than in the premarketing data. Adverse events were generally transient, and characteristics of these adverse events were generally similar between the premarketing and postmarketing experience. CONCLUSION: Postmarket analyses are limited by significant underreporting, and in the case of ocriplasmin as a first in-class drug, they may not have captured safety events that have only more recently been identified. Nonetheless, postmarket analyses can identify the scope of potential safety events based on real-world experiences. Ocriplasmin administration should be guided by an appropriate and informed risk-benefit discussion with the patient. Ongoing active postmarket surveillance by all practitioners will continue to be critical to better understand this safety profile.

Efficacy of glycerol and flax seed oil as anti-adhesive barriers after thyroidectomy.

BACKGROUND: We evaluated the effects of local flax seed oil and glycerol application for reducing adhesion formation after thyroidectomy. MATERIAL AND METHODS: We randomly assigned 18 female Wistar albino rats (median weight: 275 g, median age: 4.5 mth) to 3 groups: 0.1 ml 0.9% NaCl, glycerol, and flax seed oil were sprayed in a perithyroidal area after thyroidectomy operation on all animals as anti-adhesive barriers. Rats were sacrificed on the postoperative 14th day and adhesions were evaluated macroscopically and microscopically. RESULTS: The median macroscopic adhesion score was 3.0±0.0 in the 0.9% NaCl group, 1.33±0.52 in the glycerol group, and 1.67±0.53 in the flax seed oil group. The median histopathological fibrosis scores were 2.33±0.82, 0.67±0.52, and 0.83±0.75, respectively. Both glycerol and flaxseed oil group macroscopic and microscopic scores were significantly lower than the 0.9% NaCl group (p<0.05). There was no significant difference among the groups (p>0.05). CONCLUSIONS: Glycerol and flax seed oil both decrease the incidence of post-thyroidectomy adhesion in rats, but glycerol is more effective.