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| 2. |
- Axelsson, Jakob B, et al.
(author)
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Intestinal bacteria and permeability during experimental acute pancreatitis in rats
- 2006
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In: Annals of Gastroenterology. - 1108-7471. ; 19:3, s. 276-284
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Journal article (peer-reviewed)abstract
- Background: An increase in intestinal permeability and subsequent bacterial translocation has been demonstrated in critical illness. Cellulose derivatives have in the past been shown to reduce gut leakage following liver resection. Aims: The aim of the present study was to evaluate changes in microbial counts in experimental acute pancreatitis and the effect of pre-treatment with cellulose derivatives and N-acetyl cysteine. Subjects: 92 male Sprague Dawley rats. Methods: Acute pancreatitis was induced by intraductal taurodeoxycholic acid infusion. Animals received oral pretreatment and were randomized to either sham operation or the pancreatitis groups, with or without pre-treatment with cellulose derivatives, the antioxidant or their combinations. Intestinal bacterial populations and permeability were evaluated using bacterial counts and Ussing chamber, respectively. Results: The number of E. coli increased in the luminal content and ileal and colonic mucosa, but levels were restored to almost those seen in controls in all pre-treatment groups except for N-acetyl cysteine. When intestinal permeability was measured, none of the treatment groups showed significant differences compared to challenge, except for Nacetyl cysteine, which significantly increased permeability. Conclusion: Pre-treatment with cellulose derivatives was more efficient against disturbances in intestinal permeability and microbial populations than the antioxidant Nacetyl cysteine.
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- Nehéz, Laszlo, et al.
(author)
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Differently charged polypeptides in the prevention of post-surgical peritoneal adhesions.
- 2007
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 42:4, s. 519-523
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Journal article (peer-reviewed)abstract
- Objective. Peritoneal adhesions develop after almost all surgical interventions in the abdomen. We have developed an efficient treatment against post-surgical adhesions consisting of a combination of positively charged poly-L-lysine and negatively charged poly-L-glutamate. The aim of the present study was to further develop the concept of applying oppositely charged polypeptides in the prevention of adhesion formation, by evaluating different doses of the peptides, alterations in the way of administration, and also testing alternative components. Material and methods. Eighty-five NMRI mice were divided into six groups. A standardized peritoneal injury model was used. The groups received physiologic sodium chlorine, poly-L-lysine + poly-L-glutamate, low molecular weight poly-L-lysine + poly-L-glutamate, locally administered poly-L-lysine + poly-L-glutamate, in vitro mixed poly-L-lysine + poly-L-glutamate and poly-L-arginine + poly-L-glutamate, respectively. After 7 days, the extent of adhesion formation was determined during relaparotomy and was expressed as the mean percentage of the total wound length. Results. A significant decrease (p < 0.001) in the peritoneal adhesion rate was detected in all groups, with the exception of the group administered poly-L-arginine. Among those animals that received poly-L-lysine and poly-L-glutamate, the low dose of poly-L-lysine administration resulted in the most pronounced anti-adhesive effect. Conclusions. The most effective polypeptide combination was poly-L-lysine and poly-L-glutamate, also showing effectiveness when used at low doses and by local application. The differences in adhesion prevention and the possible underlying mechanisms are discussed and the key role of poly-L-lysine is elucidated.
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- Nehéz, Laszlo, et al.
(author)
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Prevention of postoperative peritoneal adhesions: Effects of lysozyme, polylysine and polyglutamate versus hyaluronic acid
- 2005
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 40:9, s. 1118-1123
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Journal article (peer-reviewed)abstract
- Objective. Intraperitoneal adhesions are an important cause of postoperative intestinal obstruction, abdominal discomfort and infertility. In the present study we hypothesized that a combination of polypeptides with different surface properties, resulting in fine disperse low-soluble complexes, could be of benefit in the prevention of abdominal adhesions. Material and methods. Various polypeptides including lysozyme, polyglutamate, polylysine and combinations of all three were evaluated as compared to hyaluronic acid. A standard wound on the parietal peritoneum in mice was used and the evaluated agents were administered immediately postoperatively. The extent of peritoneal adhesions to the injured area was measured and expressed as a percentage of the wound length as evaluated after 7 days. Flow cytometry was performed to evaluate the effect on peritoneal macrophage survival and phagocytic function and the Pick test was used to determine peroxide production in order to estimate toxicity and potential impairment of macrophage function caused by the chemicals. Results. Significant differences were seen among the treatment groups (p< 0.001). Both polyglutamate and lysozyme, and polyglutamate together with polylysine significantly decreased adhesion formation as compared to hyaluronic acid. The polylysine - polyglutamate combination was still visible macroscopically on the peritoneal surface after 1 week, though not after 1 month. The polyglutamate - lysozyme mixture was less effective than these individual components alone. The chemicals did not show any toxic effects or altered function in macrophage cell culture. Conclusions. Lysozyme, polyglutamate and, most effectively, a polyglutamate - polylysine combination significantly decreased experimental abdominal adhesion formation. A strong mechanical connection to the wound and prolonged attendance in the surface were noted. Peritoneal phagocyte function did not seem to be influenced by the chemicals.
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| 8. |
- Nehéz, Laszlo
(author)
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PREVENTION OF POSTSURGICAL ABDOMINAL ADHESIONS BY POLYPEPTIDES
- 2006
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Doctoral thesis (other academic/artistic)abstract
- Peritoneal adhesions develop after almost all abdominal surgical interventions and represent an important cause of postoperative intestinal obstruction, abdominal discomfort and infertility. Postoperative adhesions can potentially be reduced by using different antiadhesive agents. In the present study, we hypothesized that a combination of oppositely charged polypeptides could effectively decrease abdominal adhesions. Various polypeptides, including lysozyme, polyglutamate, polylysine and combinations of these were evaluated as compared to hyaluronic acid. A standard wound on the parietal peritoneum in mice was used and the evaluated agents were administered immediately postoperatively. The length of the peritoneal adhesions to the injured area was measured and expressed in percentage of the wound length as evaluated after 7 days. Flow cytometry was performed to evaluate the effect on peritoneal macrophage survival and phagocytic function and Pick test was used to determine peroxide production in order to estimate toxicity and potential impairment of macrophage function. Peritoneal swabs, including the wound area, were stained in order to determine the peritoneal location and clearance of the polypeptides. Electron microscopy was performed to analyze the wound surface and the ultra-structural changes of the phagocytes in cell culture. A reduced dose of polylysine and polyglutamate and local application on the injured peritoneal site were tested prior to the use of polyarginine, representing a potential alternative to polylysine. An ileocolic anastomosis was performed under both ?clean? and ?septic? conditions in the rat. In the presence of tested polypeptides, abdominal adhesions, anastomosis leakage and burst pressure were analysed after 1, 3, 5 and 7 days in the clean anastomosis model and after 7 days in the septic model. The combination of polylysine and polyglutamate significantly reduced postsurgical peritoneal adhesions in all experimental groups. This combination was biodegradable and did not alter the basic functions of peritoneal macrophages and showed no direct cytotoxicity. The insoluble test material specifically adhered to the injured peritoneum, and increased colonic anastomosis safety during the first postoperative days. In conclusion, a strong mechanical connection of the polylysine and polyglutamate complex occurred to the wound, and by prolonged attendance on the surface resulted in an effective prevention against peritoneal adhesions.
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| 9. |
- Tingstedt, Bobby, et al.
(author)
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Effect of bioactive polypeptides on leaking large bowel anastomosis and intestines in the rat.
- 2007
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In: Journal of Investigative Surgery. - : Informa UK Limited. - 0894-1939 .- 1521-0553. ; 20:4, s. 229-235
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Journal article (peer-reviewed)abstract
- Anastomotic leakage and postoperative adhesions represent major complications after colorectal surgery. We have previously shown a positive effect on both anastomotic strength and abdominal adhesions by the use of differently charged bioactive polypeptides. The present study aimed to investigate the effect of the same polypeptides on the healing of an insufficient intestinal anastomosis, as well as on accidental intestinal injury, in addition to measuring the preventive effect against the development of abdominal adhesions. An insufficient, and thereby potentially leaking, intestinal anastomosis and punctures of the intestine ("accidental intestinal injury model") were performed in rats. The treatment groups received intraperitoneal administration of poly-L-lysine and poly-L-glutamate, while controls received sodium chloride. Burst pressure, extent of abdominal adhesions, and postoperative complications were analyzed in both experimental models. A significant decrease of adhesions was seen in all animals treated with polypeptides (p < .05). Burst pressure was significantly higher (p < .001) in animals with intestinal perforation as seen on day 1 and then decreasing. A significant decrease in the incidence of peritonitis was also noted early (day 1) in this model (p = .002). The mortality and complications were high in the intestinal anastomosis model, though not affected by treatment with polypeptides. Intraabdominal adhesions were significantly reduced using polypeptides in this study, with no observed effect on other postsurgical complications. There were signs of less infectious complications in polypeptide treated animals. In animals with accidental intestinal injury, a higher burst pressure was noted in treated animals.
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| 10. |
- Tingstedt, Bobby, et al.
(author)
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Efficacy of Bioactive Polypeptides on Bleeding and Intra-Abdominal Adhesions.
- 2007
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In: European Surgical Research. - : S. Karger AG. - 0014-312X .- 1421-9921. ; 39:1, s. 35-40
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Journal article (peer-reviewed)abstract
- Background: Perioperative bleeding and postoperative adhesions are two problems encountered in abdominal surgery. Commercial products are available that decrease both bleeding and development of abdominal adhesions, but no products are effective in both situations. The combination of differently charged bioactive polypeptides, administered intraperitoneally, has previously been shown effective in decreasing postoperative adhesions. The present study is a pilot examination of the effects on perioperative bleeding and postoperative adhesions, applying the polypeptide concept. Methods: Standardized wounds in the liver and spleen were induced in 52 NMRI mice. The amounts of bleeding and postoperative adhesions were measured after 1 and 7 days, respectively. Separate animals were examined after 8 weeks for long-term healing of the parenchymal wounds. Results: Both parenchymal bleeding and the extent of adhesions significantly decreased (p=0.001 and p=0.029, respectively) as compared to controls. Histology after 8 weeks showed no clear signs of impaired or altered healing. Conclusion: Intraperitoneal administration of differently charged polypeptides significantly decreased postoperative bleeding and postoperative adhesions. Bioactive polypeptides appear promising in the promotion of peritoneal healing and merits further studies.
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| 12. |
- Tingstedt, Bobby, et al.
(author)
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Late Abdominal Complaints after Appendectomy - Readmissions during Long-Term Follow-Up.
- 2004
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In: Digestive Surgery. - : S. Karger AG. - 0253-4886 .- 1421-9883. ; 21:1, s. 23-27
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Journal article (peer-reviewed)abstract
- <i>Background/Aims:</i> The postoperative risk of small bowel obstruction is a recognized complication following appendectomy. Few studies have reconsidered the whole extent of abdominal complaints and problems following appendectomy. This study tries to evaluate the long-term outcome describing abdominal complaints requiring readmission following appendectomy. <i>Methods:</i> A retrospective study of 3,230 patients undergoing open appendectomy at a single center university hospital in Sweden between 1981 and 1996. Late (>30 days) readmissions were noted and the cause for readmission and need for surgical intervention were analyzed. <i>Results:</i> Overall, late readmissions occurred in 2.94% during a median follow-up of 10 years after appendectomy. Females predominated among those readmitted, as did patients with complicated appendicitis or a ‘normal’ appendix. Nonspecific abdominal pain with no sign of small bowel obstruction caused almost half of the readmissions (45%). To a large extent this group consisted of females (76%). Small bowel obstruction was seen in 1.24% and was surgically treated in 0.68% of all appendectomies. Incisional hernias were also seen (0.4% of all appendectomies). <i>Conclusion:</i> The magnitude of readmissions due to abdominal complaints is more pronounced than previously reported with as many patients with signs of small bowel obstruction managed nonoperatively as surgically, and frequent readmissions due to nonspecific abdominal pain.
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