Novel macromolecular crosslinking hydrogel to reduce intra-abdominal adhesions.

BACKGROUND: The aim of this study was to compare the anti-adhesion efficacy of a biodegradable, in situ, macromolecular cross-linking hydrogel made from oxidized dextran/N-carboxyethyl chitosan (Odex/CEC) with a commercially available carboxymethylcellulose/modified hyaluronan barrier film (Seprafilm; Genzyme Corporation, Cambridge, MA) in a rat cecum abrasion model. METHODS: The rat model utilized a cecal abrasion and abdominal wall insult surgical protocol. The 2% Odex/CEC hydrogel treatment was applied by syringe to coat both the cecal and the abdominal wall insults, while other animals were treated with Seprafilm applied to the cecal injury only. Control animals did not receive any treatment. Animals were sacrificed after post operative day 21 and adhesion severity was quantitatively graded using a whole number scale from 0 - 3. Histological analysis was also performed for animals receiving Odex/CEC hydrogel treatment and no treatment (control). RESULTS: Mean adhesion score was 2.09+/-1.22 for control animals, 1.00+/-1.00 for 2% Odex/CEC hydrogel animals, and 1.25+/-1.22 for Seprafilm animals. Hydrogel treated animals showed significantly lower adhesion scores than control animals (P<0.05), while Seprafilm demonstrated a marginally lower adhesion score (P<0.1) compared with the controls. Histological analysis of an Odex/CEC treated rat showed tissue repair and small fragments of hydrogel inside both healed abdominal and cecal surfaces. CONCLUSIONS: Both Seprafilm and the 2% Odex/CEC hydrogel showed a significantly decreased adhesion score compared with the control. However, the hydrogel, compared with Seprafilm, offers ease of application and ability to conform to complex tissue geometries that could provide surgeons with another prophylactic treatment to prevent abdominal adhesions.

Cross-linked hyaluronic acid films to reduce intra-abdominal postsurgical adhesions in an experimental model.

BACKGROUND/AIMS: Intra-abdominal adhesions typically occur after surgically damaged tissues are situated in apposition, leading to fibrotic connections. The goal of this study was to demonstrate the in vivo efficacy of a cross-linked and insoluble hyaluronic acid (HA) film to reduce postsurgical adhesion in a rat model. METHODS: To measure in vitro adhesion resistance, porcine monocytes were deposited on the surface of films and their attachment was monitored by scanning electron microscopy. A rat cecum abrasion and abdominal insult model was utilized to demonstrate in vivo efficacy. Briefly, an HA film was deployed as a barrier between the damaged cecal and abdominal tissue surfaces for 21 days; control animals did not receive treatment. At the study conclusion, the rats were sacrificed and the degree of adhesion was determined using a scale from 0 to 3, where 0 = no adhesion and 3 = severe fibrosis. RESULTS: HA films resisted monocyte adhesion in vitro. The in vivo study results demonstrated a significantly lower mean adhesion score (0.625 +/- 0.517) with HA film treatment compared to the controls (2.09 +/- 1.22). CONCLUSION: Placement of HA films between injured tissues significantly decreases the severity of abdominal adhesions. Furthermore, the HA film's resistance to monocyte adhesion could be contributory to lowering in vivo adhesion scores.

A mobile cecum predisposing to a major complication of laparoscopic assisted ileostomy.

Laparoscopic-assisted stoma creation is becoming a more popular procedure in the adult surgical population. Our institution has previously reported the use of the laparoscopic assisted colostomy (LAC) in children. In this paper, we describe an important complication in a 4-year-old patient, with trisomy 21, who underwent a laparoscopic-assisted loop ileostomy (LAI) and, subsequently, developed a volvulus of the cecum around the loop ileostomy. We suggest that when LAI is performed, cecal mobility should be carefully evaluated. In the absence of adequate cecal peritoneal attachments, an additional procedure to fix the cecum should be considered to prevent a potential volvulus around the stoma.

Effects of feed supplementation with specific hen egg yolk antibody (immunoglobin Y) on Salmonella species cecal colonization and growth performances of challenged broiler chickens.

Anti-Salmonella spp. egg yolk antibodies (IgY) simultaneously directed against Salmonella Enteritidis and Salmonella Typhimurium were tested to determine if their inclusion in feed decreased Salmonella spp. cecal colonization in experimentally infected broiler chickens. Egg yolk powder (EYP) was obtained by freeze-drying egg yolks containing anti-Salmonella spp. Immunoglobin Y was included in feed at 5 levels of concentration (0 to 5%). Feeds were formulated to similar nutrient levels and provided for ad libitum intake from d 1 to 28. Three days after initiation of feed treatments (d 4), chickens were co-challenged with equal numbers of Salmonella Enteritidis and Salmonella Typhimurium (2x10(6) cfu/bird). Cecal samples were recovered weekly over the experimental period (d 7 to 28) to enumerate Salmonella spp. The effect of anti-Salmonella spp. IgY feed supplementation on growth performance of infected chickens was also evaluated during the same period. In comparison with the positive control treatment (PC), treatments involving EYP (T1, T2, T3, T4, and T5), whether containing anti-Salmonella spp. IgY or not, significantly improved (P<0.05) the growth performance of challenged chickens, but without reaching the performance levels of nonchallenged chickens (NC1 and NC2). However, no link can be established between the enhancement in growth performance of challenged birds and their contamination levels by Salmonella because in-feed incorporation of EYP had no significant effect on cecal colonization by Salmonella. Furthermore, the comparison of the 5 anti-Salmonella spp. IgY concentration levels in feed did not reveal any anti-Salmonella spp. IgY concentration effect on growth performance and Salmonella cecal colonization. These results suggest that anti-Salmonella spp. IgY would undergo denaturation and degradation after their passage through the animal gastrointestinal tract and reveal that components of EYP other than specific antibodies have a beneficial effect on growth performance.

[New aspects of pathogenesis of adhesive process in the abdominal cavity].

Adhesive process in the abdominal cavity is the leading cause of morbidity and mortality in abdominal surgery. The clinical investigation included 126 children with acute adhesive intestinal obstruction. All patients were divided into two groups: polyenzyme and monoenzyme groups. In the polyenzyme group there was one case of intestinal obstruction. In the monoenzyme group there were 4 children with intestinal obstruction. The experiment included 70 adult rats divided in two equal groups: the main and control groups. The main group animals were given a polyenzyme preparation. The control group had a high incidence of cecal adhesions, which was significantly higher than the number of adhesions in the main group (Chi-square test = 23.1, df=2, p = 0.001). Proteolytic enzymes induce cells to express, de novo, the vascular endothelial growth factor, fibroblast growth factor and Laminin. As a consequence of these effects, activation of T-lymphocytes and macrophages mediating the inflammatory response will be down-regulated. It was found that the levels of VEGF, FGF and Laminin in the abdominal cavity, detected by immunohistochemistry, were different in the rats having high level and having no postoperative abdominal adhesion. The level of angiogenesis factors was also rapidly normalized by means of polyenzyme therapy.

In situ cross-linkable hyaluronic acid hydrogels prevent post-operative abdominal adhesions in a rabbit model.

We studied the efficacy of an in situ cross-linked hyaluronic acid hydrogel (HAX) in preventing post-surgical peritoneal adhesions, using a rabbit sidewall defect-cecum abrasion model. Two cross-linkable precursors were prepared by modifying hyaluronic acid with adipic dihydrazide and aldehyde, respectively. The hydrogel precursors cross-linked to form a flexible hydrogel upon mixing. The hydrogel was biodegradable and provided a durable physical barrier, which was highly effective in reducing the formation of post-operative adhesions. Ten out of 12 animals in the untreated control group developed fibrous adhesions requiring sharp dissection, while only 2 out of 8 animals treated with HAX gels showed such adhesions, and those occurred in locations that were not covered by the hydrogel. We also studied means by which gel degradation time can be modulated by varying the precursor concentration and molecular weight.

Schinus terebinthifolius raddi (Aroeira) and Orbignya phalerata mart. (Babassu) effect in cecorrahphy healing in rats.

PURPOSE: To evaluate the effect of Schinus terebinthifolius Raddi (aroeira) and Orbignya phalerata Mart. (babassu) in the healing process of cecorrhaphy in rats. METHODS: : Fifty four rats were used, distributed into three groups randomly: aroeira, babassu and control, which were divided into three subgroups (six animals) according to the time of the deaths (7, 14, 21 days). All underwent the same surgical procedure, cecotomy and cecorrhaphy. The animals in group aroeira and babassu received daily dose of 100 mg/kg of hydroalcoholic extract and 50 mg/kg of aquous extract respectively, by gavage. The control group received only saline solution. The parameters evaluated were: macroscopic changes, ,resistance test to air insufflations and histological changes. RESULTS: : All animals showed good healing without infection. All groups presented adhesions between cecum and neighboring organs. The resistance test insufflating of atmospheric air showed progressive increase of pressure according to the days in the aroeira group, and decrease in babassu group, without significant difference. Microscopy showed significant difference in the polymorphonuclear, hyperemia, angiogenesis, fibroblast proliferation and collagen histological variables in the 14th day. CONCLUSION: : Hydroalcoholic extract of aroeira and the aqueous extract of babassu favored the healing process in cecorrhaphy in rats.

The potential efficacy of Survanta (r) and Seprafilm (r) on preventing intra-abdominal adhesions in rats.

PURPOSE: To investigate the potential efficacy of beractant (Survanta(r)) and Seprafilm(r) on the prevention of postoperative adhesions. METHODS: Forty Wistar-albino female rats were used. The rats were randomly allocated into four groups of 10 rats each as control group (CG), beractant group (BG), Seprafilm(r) group (SG), and combined group (COG). All rats underwent cecal abrasion via midline laparotomy. Before abdominal closure, isotonic saline, beractant, Seprafilm, and combined agents were intraperitoneally administered. Adhesions were classified macroscopically with Canbaz Scoring System on postoperative day 10. Ceacum was resected for histopathological assessment. RESULTS: Macroscopic adhesion scores were significantly lower in BG, SG, and COG than CG (p<0.05); (45%, 15%, 25%, and 15%; respectively). Histopathological assessment revealed a reduced inflammation and fibrosis score in the study groups than CG (p<0.05). In BG, adhesion development, inflammation and fibrosis scores were lower than SG; however, it was not statistically significant. CONCLUSIONS: Intra-abdominal application of beractant is significantly effective for the prevention of adhesion formation with no adverse effect by covering the whole peritoneal mesothelium with excellent gliding properties in a rat model. The combination of both agents is also effective in reducing adhesion formation, however, not superior to single beractant application.

Analysis of the kinetics of peritoneal adhesion formation in the rat and evaluation of potential antiadhesive agents.

BACKGROUND: Peritoneal adhesions continue to be a significant cause of postoperative complications. Elucidating the origin of these adhesions has been hampered by the lack of a reproducible animal model. The purpose of this study was to create a standardized model in which a single, specific adhesion could be objectively measured. With this model the kinetics of adhesion formation were then evaluated. A variety of potential antiadhesive agents were then tested and compared. METHODS: In this study a reproducible, quantitative rat model was developed that used uniform defects on the peritoneal wall and cecal surface. The resulting adhesions were subsequently scored, and their strength was measured with a tensiometer. An evaluation of the kinetics of peritoneal adhesion formation was obtained by using a timed removal of silicone elastomer sheeting held between the two injured surfaces. The following antiadhesive agents were evaluated: Ringer's lactate solution; dextran 70 (32%); modified carboxymethylcellulose (1.0% and 2.0%); an absorbable barrier of specially knitted material composed of oxidized regenerated cellulose; fibrin sealant; silicone elastomer film; and expanded polytetrafluoroethylene membrane. RESULTS: Evaluation of the kinetics of peritoneal adhesion formation indicated that the susceptibility for adhesion formation was significantly decreased or eliminated after the first 36 hours. Evaluation of antiadhesion agents indicated that the magnitude of adhesion prevention was directly proportional to the agent's ability to remain at the site of injury during the critical period of adhesion formation. Permanent barriers (silicone elastomer film, expanded polytetrafluoroethylene membrane) provided the greatest antiadhesion effect but were not believed to be ideal agents because they remained at the site of injury well after the critical period of adhesion formation. The incidence of adhesion formation for the other agents was as follows: control (34 of 34), Ringer's lactate (12 of 12), absorbable barrier of knitted cellulose (10 of 10), 32% dextran 70 (8 of 12), 1% carboxymethylcellulose (6 of 12), fibrin sealant (4 of 9), and 2% carboxymethylcellulose (4 of 12). CONCLUSIONS: The efficacy of antiadhesion agents appears to be related to the agent's viscosity, ability to coat the wound surface, and residence time at the site of injury. In this rat model an agent that remained on the injured surfaces for at least 36 hours after injury appeared to be more effective in reducing adhesion formation than an agent with a shorter residence time.

A hyaluronate based gel for the prevention of postsurgical adhesions: evaluation in two animal species.

OBJECTIVE: To assess in two animal surgery models, the efficacy of a bioabsorbable gel to prevent postoperative adhesions. DESIGN: A randomized, prospective, blinded study using animal abdominal surgery models. SETTING: Two animals species with surgical traumas to induce adhesion formation. INTERVENTIONS: A chemically modified hyaluronate and carboxymethylcellulose-based gel formulation. MAIN OUTCOME MEASURES: The number of animals with no adhesions, mean number of adhesions, and total adhesion score. RESULTS: Treatment with the bioabsorbable gel increased the number of animals without any adhesion by 70% in a rat cecal abrasion model and by > 90% in a rabbit sidewall defect-bowel abrasion model when compared with nontreatment control animals. Other outcome measures showed similar efficacy. CONCLUSION: The modified hyaluronate-carboxymethylcellulose gel was effective in two animal species after surgery in the abdominal cavity. The gel appears to act as a physical barrier between damaged peritoneal tissue and may be appropriate for human clinical trials in open and laparoscopic surgical procedures.

Evaluation of the SprayGel adhesion barrier in the rat cecum abrasion and rabbit uterine horn adhesion models.

OBJECTIVE: To evaluate the efficacy of a new adhesion barrier in the prevention of postoperative adhesion formation. DESIGN: A double-blind controlled study of the efficacy of SprayGel in reducing postoperative adhesion formation in two animal models. SETTING: Animal care facility of a contract testing laboratory. ANIMAL(S): Sixteen Sprague-Dawley male rats were randomly allocated into two groups in the cecum abrasion model. Twenty New Zealand white female rabbits were randomly allocated into two groups in the uterine horn abrasion model. INTERVENTION(S): In the rat model, the cecum was abraded with gauze and the abdominal wall was abraded with a scalpel. Treated animals received SprayGel coating on injured surfaces; control animals received no treatment. In the rabbit model, uterine horns were abraded with a scalpel. Treated animals received SprayGel coating on injured surfaces; control animals received no treatment. MAIN OUTCOME MEASURE(S): Postoperative adhesion formation. RESULT(S): In the rat model, SprayGel was found to significantly reduce the incidence of adhesions, which formed in 7 of 8 control rats compared with 1 of 8 treated rats. In the rabbit model, SprayGel was found to significantly reduce both the extent and severity of adhesions. CONCLUSION(S): Application of SprayGel in two animal models reduced formation of postoperative adhesions. Further investigation in large animal and clinical settings is warranted.

Colonic pseudo-obstruction in burns patients.

Acute pseudo-obstruction is a rare complication in burns patients. An awareness of the factors implicated in its pathogenesis such as prolonged bed rest, narcotic medications, hypokalaemia, sepsis and surgery (all commonly associated with burns patients) is essential if this condition is to be avoided. Early diagnosis, prokinetic and cathartic agents, and aggressive endoscopic intervention are essential to halt the progression of caecal dilatation. Excisional surgery and stoma formation are necessary for salvage of complicated colonic pseudo-obstruction.

Efficacy of tenoxicam on intra-abdominal adhesion prevention in a rat model.

The aim of this study was to investigate the effect of tenoxicam as a non-steroidal anti-inflammatory drug (NSAID) on intra-abdominal adhesion prevention in a rat model. Altogether 50 Wistar-Albino rats weighing 220-280 g were assigned to five groups, each of which was made up of 10 rats. All the rats were anaesthetized and prepared for sterile surgery. After a mid-line laparotomy was performed, a 1 cm area of the caecum was rubbed with gauze until subserosal haemorrhage developed, and then a 5 mm-diameter part of the peritoneum on the right side of the abdominal wall was removed. Prior to complete closure, 3 ml of the test material was placed into the abdominal cavity. On the eighth day the rats were killed and the adhesion score was determined. The groups and their mean adhesion scores were as follows: control group (normal saline), 2.5; group of dilution buffer, 1.8; tenoxicam (0.125 mg/kg), 1.3; tenoxicam (0.25 mg/kg), 1.3; and tenoxicam (0.5 mg/kg), 0.9. The differences between the adhesion scores among all the groups (P < 0.05, Kruskal-Wallis test), and those between the tenoxicam groups and control group (P < 0.05, Mann-Whitney U-test), were significant. Thus a single instillation of tenoxicam into the peritoneal cavity at the time of surgery reduced adhesion formation effectively in this model, irrespective of dosage.

alpha-Difluoromethylornithine: a promising lead for preventive chemotherapy for coccidiosis.

alpha-Difluoromethylornithine (DFMO; RMI 71,782) given in drinking water in concentrations as low as 0.0625% inhibited infections of Eimeria tenella and minimized the development of lesions in chickens. It had approximately the same activity as a currently used anticoccidial drug, amprolium, and also had the advantage of being relatively nontoxic in chickens. Body weight gains were not reduced in chickens given 0.0635% DFMO or less for 14 days starting 8 days before they were inoculated with oocysts, but were reduced in chickens given drinking water containing 0.125 and 0.25% DFMO. The anticoccidial activity of DFMO was completely reversed by injection (intraabdominal) of putrescine hydrochloride (300 mg/kg of body weight/day), indicating that the drug may act by blocking putrescine biosynthesis. Inoculated chickens, in which coccidial lesion development was suppressed by DFMO, resisted subsequent challenge exposure with E tenella, as did nontreated infected control birds which had recovered from infection.

Intra-abdominal adhesions and their prevention by topical tissue plasminogen activator.

Recent work shows that a common pathway in adhesion production is a reduction in local plasminogen activator activity (PAA). This deficit permits deposited surface fibrin to become organized to fibrous adhesions. A rabbit model for adhesion formation was used to assess the effect of replacing the deficit with recombinant tissue plasminogen activator (rt-PA). Adhesions were produced by stripping peritoneum from corresponding parietal and visceral areas. One week later the adhesions were divided. Either rt-PA or placebo was applied to the divided adhesion. After a further week the animal was killed and the adhesions assessed. Sixty strips were performed. Fifty-five adhesions were produced (92%). Placebo gel was applied to 28 sides and rt-PA applied to 27. Twenty-two of the placebo group recurred (79%). Two of the rt-PA group reformed (7%, chi 2 = 20.883, P less than 0.001). Recombinant tissue plasminogen activator is an effective inhibitor of adhesion formation in the experimental animal.

[Synergic effect of Dextran 70 at 32% and an antibiotic in the prevention of peritoneal adhesions. Experimental study in rats]. / Effet synergique du Dextran 70 à 32% et d'un antibiotique dans la prévention des adhérences péritonéales. Etude expérimentale chez le rat.

In an experimental study we evaluate the anti-adherential effect of four different solutions: physiological serum, Chloramphenicol, Dextran 70 (32%) and the association of these last two solutions. Synergic effect is shown when using an antibiotic (Chloramphenicol) with a non-bactericid solution (Dextran). Comparing our results with current literature, we are confident on the efficacity of similar association concerning other solutions than Dextran 70 (32%).

[Prevention of adhesions after appendectomy]. / O profilaktike apaek posle appendektomii.

The author suggests a modification of the invagination method of appendectomy without ligation of the stump. This method is the most physiologic one; it minimizes the inflammatory process and prevents an undue formation of adhesions. Experimental grounds for the method are described. 204 patients were operated upon. This method has shown better long-term results as compared to typical appendectomy.

Biodegradable and thermosensitive monomethoxy poly(ethylene glycol)-poly(lactic acid) hydrogel as a barrier for prevention of post-operative abdominal adhesion.

Post-operative peritoneal adhesions are serious consequences of abdominal or pelvic surgery and cause severe bowel obstruction, chronic pelvic pain and infertility. In this study, a novel nano-hydrogel system based on a monomethoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) di-block copolymer was studied for its ability to prevent abdominal adhesion in rats. The MPEG-PLA hydrogel at a concentration of 40% (w/v) was injected and was able to adhere to defect sites at body temperature. The ability of the hydrogel to inhibit adhesion of post-operative tissues was evaluated by utilizing a rat model of abdominal sidewall-cecum abrasion. It was possible to heal wounded tissue through regeneration of neo-peritoneal tissues ten days after surgery. Our data showed that this hydrogel system is equally as effective as current commercialized anti-adhesive products.

Schinus terebinthifolius raddi (Aroeira) and Orbignya phalerata mart. (Babassu) effect in cecorrahphy healing in rats

ABSTRACT PURPOSE: To evaluate the effect of Schinus terebinthifolius Raddi (aroeira) and Orbignya phalerata Mart. (babassu) in the healing process of cecorrhaphy in rats. METHODS : Fifty four rats were used, distributed into three groups randomly: aroeira, babassu and control, which were divided into three subgroups (six animals) according to the time of the deaths (7, 14, 21 days). All underwent the same surgical procedure, cecotomy and cecorrhaphy. The animals in group aroeira and babassu received daily dose of 100 mg/kg of hydroalcoholic extract and 50 mg/kg of aquous extract respectively, by gavage. The control group received only saline solution. The parameters evaluated were: macroscopic changes, ,resistance test to air insufflations and histological changes. RESULTS : All animals showed good healing without infection. All groups presented adhesions between cecum and neighboring organs. The resistance test insufflating of atmospheric air showed progressive increase of pressure according to the days in the aroeira group, and decrease in babassu group, without significant difference. Microscopy showed significant difference in the polymorphonuclear, hyperemia, angiogenesis, fibroblast proliferation and collagen histological variables in the 14th day. CONCLUSION : Hydroalcoholic extract of aroeira and the aqueous extract of babassu favored the healing process in cecorrhaphy in rats.

The potential efficacy of Survanta (r) and Seprafilm (r) on preventing intra-abdominal adhesions in rats

ABSTRACT PURPOSE: To investigate the potential efficacy of beractant (Survanta(r)) and Seprafilm(r) on the prevention of postoperative adhesions. METHODS: Forty Wistar-albino female rats were used. The rats were randomly allocated into four groups of 10 rats each as control group (CG), beractant group (BG), Seprafilm(r) group (SG), and combined group (COG). All rats underwent cecal abrasion via midline laparotomy. Before abdominal closure, isotonic saline, beractant, Seprafilm, and combined agents were intraperitoneally administered. Adhesions were classified macroscopically with Canbaz Scoring System on postoperative day 10. Ceacum was resected for histopathological assessment. RESULTS: Macroscopic adhesion scores were significantly lower in BG, SG, and COG than CG (p<0.05); (45%, 15%, 25%, and 15%; respectively). Histopathological assessment revealed a reduced inflammation and fibrosis score in the study groups than CG (p<0.05). In BG, adhesion development, inflammation and fibrosis scores were lower than SG; however, it was not statistically significant. CONCLUSIONS: Intra-abdominal application of beractant is significantly effective for the prevention of adhesion formation with no adverse effect by covering the whole peritoneal mesothelium with excellent gliding properties in a rat model. The combination of both agents is also effective in reducing adhesion formation, however, not superior to single beractant application.