icodextrin and Disease-Models--Animal

Metabolic syndrome (MetS) is commonly observed among peritoneal dialysis (PD) patients, and hyperbranched polyglycerol (HPG) is a promising glucose-sparing osmotic agent for PD. However, the biocompatibility of a HPG-based PD solution (HPG) in subjects with MetS has not been investigated. This study compared the local and systemic effects of a HPG solution with conventional physioneal (PYS) and icodextrin (ICO) PD solutions in rats with MetS. Obese type 2 diabetic ZSF1 rats received a daily intraperitoneal injection of PD solutions (10 mL) for 3 months. The peritoneal membrane (PM) function was determined by ultrafiltration (UF), and the systemic responses were determined by profiling blood metabolic substances, cytokines and oxidative status. Tissue damage was assessed by histology. At the end of the 3-month treatment with PD solutions, PM damage and UF loss in both the PYS and ICO groups were greater than those in the HPG group. Blood analyses showed that compared to the baseline control, the rats in the HPG group exhibited a significant decrease only in serum albumin and IL-6 and a minor glomerular injury, whereas in both the PYS and ICO groups, there were more significant decreases in serum albumin, antioxidant activity, IL-6, KC/GRO (CXCL1) and TNF-α (in ICO only) as well as a more substantial glomerular injury compared to the HPG group. Furthermore, PYS increased serum creatinine, serum glucose and urine production. In conclusion, compared to PYS or ICO solutions, the HPG solution had less adverse effects locally on the PM and systemically on distant organs (e.g. kidneys) and the plasma oxidative status in rats with MetS.

Topics: Animals; Biomarkers; Cytokines; Diabetes Mellitus, Type 2; Dialysis Solutions; Disease Models, Animal; Glycerol; Icodextrin; Inflammation Mediators; Injections, Intraperitoneal; Kidney; Male; Obesity; Organic Chemicals; Oxidative Stress; Peritoneal Dialysis; Peritoneum; Permeability; Polymers; Rats, Zucker; Time Factors

The purpose of this study was to compare the effects of thymoquinone and icodextrin in rats within the framework of an experimental adhesion model.. Rats were separated into three groups: (1) a control group consisting of rats that had 2 ml of isotonic solution administered intraperitoneally, (2) an ICO group administered with 2 ml of 4% icodextrin, and (3) a TQ group administered thymoquinone (10 mg/kg), all following cecal abrasion. The three groups underwent a reoperation on the 7th postoperative day. Hydroxyproline levels were analyzed in the resected adhesive tissues, and histopathological investigations were conducted. Blood samples were collected for biochemical analyses.. Fewer postoperative adhesions were observed in the ICO and TQ groups compared with the control group. A comparison of the TQ and ICO groups revealed lowers levels of postoperative adhesions in the TQ group. Compared with the control group, malondialdehyde, 8-OH-deoxyguanosine/deoxyguanosine (8-OHdG/10dG), Coenzyme Q10 (CoQ10), and CoenzymeQ10/reduced CoenzymeQ10 (CoQ10/CoQ10H) values were found to be lower in the TQ and ICO groups. When the TQ and ICO groups were compared with respect to their biochemical parameters, the results for all of the four parameters were found to be statistically significantly lower in the TQ group (P < 0.000). The levels of hydroxyproline in the control, ICO, and TQ groups were found to be (mean ± standard deviation) 502.25 ± 90.39 μg/g, 342.13 ± 66.61 μg/g, and 287.88 ± 49.59 μg/g, respectively.. A comparison of the antiadhesive effects of thymoquinone and icodextrin revealed thymoquinone to be more effective. These results indicate that thymoquinone is an efficient and strong antiadhesive molecule.

Topics: Animals; Benzoquinones; Disease Models, Animal; Glucans; Glucose; Humans; Icodextrin; Injections, Intraperitoneal; Male; Postoperative Complications; Rats; Rats, Wistar; Tissue Adhesions; Ubiquinone

The aim of this experimental study was to investigate whether spinal epidural 4% glucose polymer solution is effective in the prevention of postoperative fibrosis.. Twenty eight adult Wistar albino rats were randomly divided into two equal groups, including treatment and control. Both groups underwent L1 vertebral total laminectomy to expose the dura. Topical treatment group received 4% icodextrin. Four weeks later, epidural fibrosis was examined in both groups histologically, biochemically and macroscopically.. Topical use of 4% icodextrin prevented significantly epidural fibrosis following the laminectomy operation.. Topical 4% icodextrin application inhibits postoperative epidural fibrosis with various mechanisms and prevents adhesions by playing barrier role between tissue surfaces through flotation. Our study is first to present evidence of experimental epidural fibrosis prevention with 4% icodextrin.

Topics: Animals; Dialysis Solutions; Disease Models, Animal; Epidural Space; Fibrosis; Glucans; Glucose; Icodextrin; Laminectomy; Male; Postoperative Complications; Rats; Rats, Wistar; Spinal Diseases

There is no standard treatment in patients with high risk metachronous peritoneal carcinomatosis (PC) in colonic cancer, as perforated tumour or synchronous ovarian metastasis. Icodextrin 4% (ICDX), presently used to prevent postoperative abdominal adhesions, could inhibit the coactivation of the tumour cells and the microenvironment cells, associated with the development of PC. The aim of this study was to inhibit the formation of the PC in a murine model mimicking surgical situation using ICDX and intraperitoneal (IP) prophylactic chemotherapy. We created a model of growing PC in mice using cells of murine colonic cancer CT26. Cells and treatments were injected simultaneously. Five groups were created: CT26 (control group), CT26 + ICDX (ICDX group), CT26 + chemotherapy (oxaliplatin and 5FU) (chemo group), CT26 + chemotherapy + ICDX (ICDX chemo group), ICDX (toxicity group). At day 15, PC was evaluated with rodents PCI. In the chemo group, PCI was significantly lower than in the control group (3.2 versus 8.4, p = 0.02). ICDX had a synergetic effect on PC with chemotherapy; indeed PCI in ICDX chemo group was lower than in chemo group (1.4 versus 3.2, p = 0.04). There was no morbidity linked to ICDX in toxicity group. Safety of ICDX needs to be verified, particularly on colonic anastomosis before ICDX associated to IP chemotherapy could be used as a preventive treatment of PC in high risk patients. This prophylactic treatment is easy to use and would be administrated at the end of a curative surgery for a colonic cancer.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cell Line, Tumor; Cell Movement; Cell Survival; Colonic Neoplasms; Dialysis Solutions; Disease Models, Animal; Fluorouracil; Glucans; Glucose; Icodextrin; Infusions, Parenteral; Mice; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms

Background Postoperative adhesions are the result of aberrant peritoneal healing. As they are the leading cause of postoperative bowel obstruction, anti-adherence barriers are advocated for their prevention. This study looks into the effect of these biomaterials on the healing of intestinal anastomoses. Materials and Methods Thirty-three New Zealand White rabbits underwent laparotomy, transection of the terminal ileum, and creation of an end-to-end anastomosis. Animals were randomized into 3 groups: the Control group (n = 11); the Icodextrin group, receiving icodextrin 4% intraperitonealy (n = 11); and the HA/CMC group, having the anastomosis wrapped with a hyaluronic acid/carboxymethylcellulose film (n = 11). All animals were sacrificed on the seventh postoperative day. Macroscopic adhesions were graded and anastomotic strength was tested by the burst pressure. Histological healing was assessed in a semiquantitative way for the presence of ulceration, reepithelization, granulation tissue, inflammation, eosinophilic infiltration, serosal inflammation, and microscopic adhesions. Univariate and multivariate analysis was used. Results are given as medians with interquartile range. Results The median adhesion scores were the following: Control 1 (0-3), Icodextrin 0 (0-1), HA/CMC 0 (0-0), P = .017. The burst pressure did not differ between the groups; however, all except one bowel segments tested burst away from the anastomosis. The macroscopic and histological anastomotic healing was comparable in all 3 groups. A poor histological anastomotic healing score was associated with a higher adhesion grade (odds ratio = 1.92; 95% confidence interval = 1.06-3.47; P = .032). Conclusion Adhesion formation was inhibited by the materials tested without direct detrimental effects on anastomotic healing. Poor anastomotic healing provokes adhesions even in the presence of anti-adhesion barriers.

Topics: Anastomosis, Surgical; Animals; Biocompatible Materials; Carboxymethylcellulose Sodium; Disease Models, Animal; Glucans; Glucose; Hyaluronic Acid; Icodextrin; Ileum; Injections, Intralesional; Injections, Intraperitoneal; Laparotomy; Rabbits; Random Allocation; Reference Values; Tissue Adhesions; Treatment Outcome; Wound Healing

Cerebrospinal fluid shunt operations have reduced the morbidity and mortality of hydrocephalus, but have potential complications. Ventriculoperitoneal (vp) shunt obstruction is one of the common complications of shunt surgery. The obstruction is caused by fibrosis and is usually located on the tip of the ventricular and/or peritoneal catheter.. In our study, we aimed to demonstrate the known antifibrotic effects of heparin, hyaluronate/carboxymethylcellulose, and icodextrin on peritoneal catheter obstruction in a vp shunt model in rats.. Thirty-two male Sprague-Dawley rats were used in this study. A shunt catheter was placed in the abdominal cavity. In the control group, isotonic solution, in the study groups, heparin, sodium hyaluronate/carboxymethylcellulose (HA/CMC), and icodextrin were intraperitoneally applied. The severity of adhesions and inflammation around the peritoneal catheter was evaluated after the rats were killed on day 30.. One animal in the heparin group died due to intra-abdominal hemorrhage. We found the most adhesions in the control group. All three drugs (heparin, HA/CMC, icodextrin) were effective for adhesion prevention. HA/CMC was more effective than heparin, and icodextrin was most effective. There was a statistically significant difference between the icodextrin and the control group (p = 0.007).. The intra-abdominal instillation of icodextrin, HA/CMC, and heparin, especially icodextrin, can decrease the rate of vp shunt dysfunction by preventing formation of intraperitoneal fibrosis.

Topics: Animals; Carboxymethylcellulose Sodium; Dialysis Solutions; Disease Models, Animal; Fibrinolytic Agents; Glucans; Glucose; Heparin; Hyaluronic Acid; Icodextrin; Laxatives; Male; Peritoneal Fibrosis; Rats; Rats, Sprague-Dawley; Tissue Adhesions; Ventriculoperitoneal Shunt; Viscosupplements

Peritoneal adhesions are a well-known and frequently occurring postoperative complication. Many published studies have looked into the prophylaxis of adhesions following abdominal surgery, but only few clinically relevant agents have been reported. Most publications refer to adult patients and not to paediatric patient collectives. This experimental study in a rat model compares the effect of perfluorocarbons as adhesion prophylaxis with those of a well-known anti-adhesive agent Adept and with an untreated control group. We hypothesized that PFC might have a double effect: initially it could suppress the accumulation of monocytes and neutrophilic granulocytes, and subsequently it would work as a barrier to prevent contact between the visceral and parietal layers of the peritoneum. After a standardised operation, PFC was injected into the abdominal cavity of rats in the study group. Macroscopically, the PFC group did not fare significantly better, but nevertheless a clear tendency towards fewer adhesions after the application of PFC could be ascertained.

Topics: Animals; Disease Models, Animal; Fluorocarbons; Glucans; Glucose; Icodextrin; Peritoneal Diseases; Postoperative Complications; Rats; Rats, Wistar; Tissue Adhesions; Treatment Outcome

Icodextrin, a novel glucose polymer solution utilized for peritoneal dialysis, has been demonstrated to have prolonged intraperitoneal (IP) instillation volumes in comparison to standard PBS solutions. In an animal model of ovarian cancer, we explored whether a survival advantage exists utilizing icodextrin rather than PBS as a delivery solution for an infectivity enhanced virotherapy approach.. Initial experiments evaluated whether icodextrin would adversely affect replication of a clinical grade infectivity enhanced conditionally replicative adenovirus (Delta24-RGD). Virus was added to prepared blinded solutions of PBS or icodextrin (20%) and then evaluated in vitro in various human ovarian cancer cell lines (SKOV3.ip1, PA-1, and Hey) and in vivo in a SKOV3.ip1 human ovarian cancer IP murine model. Viral replication was measured by detecting adenovirus E4 gene levels utilizing QRT-PCR. Survival was subsequently evaluated in a separate SKOV3.ip1 ovarian cancer IP murine model. Cohorts of mice were treated in blinded fashion with PBS alone, icodextrin alone, PBS+Delta24-RGD, or icodextrin+Delta24-RGD. Survival data were plotted on Kaplan-Meier curve and statistical calculations performed using the log-rank test.. There was no adverse affect of icodextrin on vector replication in the ovarian cancer cell lines nor murine model tumor samples evaluated. Median survival in the IP treated animal cohorts was 23 days for the PBS group, 40 days for the icodextrin group, 65 days for the PBS+Delta24-RGD group, and 105 days for icodextrin+Delta24-RGD (p=0.023). Of note, 5 of the 10 mice in the icodextrin+Delta24-RGD group were alive at the end of the study period, all without evidence of tumor (120 days).. These experiments suggest that the use of dialysates such as icodextrin may further enhance the therapeutic effects of novel IP virotherapy and other gene therapy strategies for ovarian cancer. Phase I studies utilizing icodextrin-based virotherapy for ovarian cancer are currently in development.

Topics: Animals; Dialysis Solutions; Disease Models, Animal; Female; Genetic Therapy; Glucans; Glucose; Icodextrin; Infusions, Parenteral; Mice; Ovarian Neoplasms

Topics: Animals; Disease Models, Animal; Electrocoagulation; Female; Ferric Compounds; Gels; Glucans; Glucose; Hyaluronic Acid; Icodextrin; Isotonic Solutions; Laparoscopy; Peritoneum; Postoperative Complications; Rats; Rats, Sprague-Dawley; Registries; Tissue Adhesions

To compare the antiadhesion efficacy of three agents (4% icodextrin, ferric hyaluronate gel, and Ringer's lactate) in severe peritoneal trauma caused by bipolar coagulation in a laparoscopic rat model.. Prospective, randomized, blinded experimental study.. International Laparoscopic Surgery Centre, Clermont-Ferrand, France.. Female Sprague-Dawley rats.. Animals were prospectively randomized to receive one of the three agents or to be controls. Coagulation of the parietal peritoneum was performed using a bipolar 40-W current followed by administration of an antiadhesion agent. Postoperative adhesion assessment was carried out on day 7 in 42 rats.. Adhesions were scored according to their extent and severity.. Adhesions occurred in all rats, however, adhesion and vascular adhesion rate scores were significantly higher in controls compared with treated groups. Adhesions were more likely to be filmy and easily separable in the 4% icodextrin group compared with the Ringer's lactate solution group.. Adhesion scores were decreased by the use of antiadherent agents. However, no rats were found to be free of adhesions after severe peritoneal trauma induced by 40-W bipolar coagulation of the peritoneum.

Topics: Animals; Disease Models, Animal; Electrocoagulation; Female; Ferric Compounds; Gels; Glucans; Glucose; Hyaluronic Acid; Icodextrin; Isotonic Solutions; Laparoscopy; Peritoneum; Postoperative Complications; Rats; Rats, Sprague-Dawley; Ringer's Lactate; Severity of Illness Index; Tissue Adhesions

To assess whether use of antiadhesive liquids or coatings could prevent adhesion formation to prosthetic mesh.. Incisional hernia repair frequently involves the use of prosthetic mesh. However, concern exists about development of adhesions between viscera and the mesh, predisposing to intestinal obstruction or enterocutaneous fistulas.. In 91 rats, a defect in the muscular abdominal wall was created, and mesh was fixed intraperitoneally to cover the defect. Rats were divided in five groups: polypropylene mesh only (control group), addition of Sepracoat or Icodextrin solution to polypropylene mesh, Sepramesh (polypropylene mesh with Seprafilm coating), and Parietex composite mesh (polyester mesh with collagen coating). Seven and 30 days postoperatively, adhesions were assessed and wound healing was studied by microscopy.. Intraperitoneal placement of polypropylene mesh was followed by bowel adhesions to the mesh in 50% of the cases. A mean of 74% of the mesh surface was covered by adhesions after 7 days, and 48% after 30 days. Administration of Sepracoat or Icodextrin solution had no influence on adhesion formation. Coated meshes (Sepramesh and Parietex composite mesh) had no bowel adhesions. Sepramesh was associated with a significant reduction of the mesh surface covered by adhesions after 7 and 30 days. Infection was more prevalent with Parietex composite mesh, with concurrent increased mesh surface covered by adhesions after 30 days (78%).. Sepramesh significantly reduced mesh surface covered by adhesions and prevented bowel adhesion to the mesh. Parietex composite mesh prevented bowel adhesions as well but increased infection rates in the current model.

Topics: Animals; Biocompatible Materials; Coated Materials, Biocompatible; Disease Models, Animal; Glucans; Glucose; Hernia, Ventral; Hyaluronic Acid; Icodextrin; Intestine, Large; Intestine, Small; Male; Polypropylenes; Postoperative Complications; Probability; Rats; Rats, Wistar; Reference Values; Sensitivity and Specificity; Surgical Mesh; Tissue Adhesions; Treatment Outcome

Intra-abdominal adhesion formation causes significant post-operative morbidity. Controlled studies using animal models have been carried out to assess the tolerability and preventive efficacy of icodextrin solution (a biodegradable, biocompatible, glucose polymer). Reduction of adhesion formation was first evaluated in a rabbit double uterine horn model, applying 10-75 ml of 7.5 and 20%, or 50 ml of 2.5-20% icodextrin solution post-operatively. Significant increases in adhesion free sites (P < 0.005) were observed with volumes > or =25 ml, and at concentrations > or =4%. Efficacy of 50 ml 4 and 20% icodextrin was then evaluated both during and after surgery, demonstrating significant reductions in adhesion formation (P < 0. 002). In one study, intra- plus post-operative use of 4% icodextrin produced the greatest reduction of non-surgical site adhesions; in others, the post-operative effect was predominant. Post-surgical administration of 50 ml 4% icodextrin in a rabbit sidewall model also resulted in more adhesion-free animals, and a significant reduction (P < 0.001) in areas of adhesion formation and reformation. In a rat infection potentiation model, 4% icodextrin produced no difference in mortality, abscess formation or overall abscess score. These data suggest that 4% icodextrin offers a well-tolerated and effective means of reducing post-surgical adhesion formation.

Topics: Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Evaluation Studies as Topic; Female; Glucans; Glucose; Icodextrin; Infections; Postoperative Complications; Rabbits; Rats; Rats, Sprague-Dawley; Solutions; Tissue Adhesions; Uterus