| 1. |
- Akbarshahi, Hamid, et al.
(författare)
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Enrichment of Murine CD68(+)CCR2(+) and CD68(+)CD206(+) Lung Macrophages in Acute Pancreatitis-Associated Acute Lung Injury.
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Acute lung injury (ALI) is an important cause of mortality in critically ill patients. Acute pancreatitis (AP) is one of the risk factors for developing this syndrome. Among the inflammatory cells, macrophages have a key role in determining the severity of the acute lung injury. In the lungs, macrophages constitute a heterogeneous cell population distributed in different compartments. Changes in not only the macrophage count, but also in their phenotype have been seen during the course of lung injury. A murine ductal ligation model of acute pancreatitis showed substantial morphological changes in the pancreas and lungs. Immunohistochemistry showed neutrophil recruitment into both organs after 9 hours and later on. F4/80(+) cells in the pancreas increased in the ligated animals, though there was not a significant difference in their number in the lungs as compared to sham operated animals. Flow cytometry analysis of lung macrophages demonstrated an enrichment of F4/80(-) CD68(+)CCR2(+) and F4/80(-) CD68(+)CD206(+) lung macrophages in ligated animals (AP) as compared to the sham operated group. The level of interleukin-6 in plasma increased 3 hours after ligation compared to the sham operated group, as a first indicator of a systemic inflammatory response.This study suggests a role for F4/80(-) CD68(+) macrophages in the pathogenesis of acute lung injury in acute pancreatitis. Studying lung macrophages for different phenotypic markers, their polarization, activation and recruitment, in the context of acute lung injury, is a novel area to potentially identify interventions which may improve the outcome of acute lung injury.
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| 2. |
- Ansari, Daniel, et al.
(författare)
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Analysis of MUC4 Expression in Human Pancreatic Cancer Xenografts in Immunodeficient Mice.
- 2014
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Ingår i: Anticancer research. - 1791-7530. ; 34:8, s. 3905-3910
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Tidskriftsartikel (refereegranskat)abstract
- Mucin 4 (MUC4) is a cell surface glycoprotein that is overexpressed in most pancreatic tumors. The aim of the present study was to characterize MUC4 expression in experimental pancreatic cancer in order to clarify the correlation between MUC4 and pancreatic cancer histology in vivo.
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| 3. |
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| 4. |
- Ansari, Daniel, et al.
(författare)
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Comparison of MUC4 expression in primary pancreatic cancer and paired lymph node metastases.
- 2013
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 48:10, s. 1183-1187
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. Mucin 4 (MUC4) is a transmembrane glycoprotein that is expressed in pancreatic ductal adenocarcinoma (PDAC), but not in normal pancreatic tissue. MUC4 has a proposed role in pancreatic tumor progression and metastasis. The purpose of this pilot study was to investigate MUC4 expression during PDAC metastasis by comparing the expression in the primary tumor and paired lymph node metastases from the same patient. Material and methods. Surgical specimens from 17 cases of primary PDAC and paired lymph node metastases were immunohistochemically analyzed for MUC4 expression. The modified histochemical score (H-score) was used for staining assessment. Results. Positive staining for MUC4 was detected in most primary and metastatic PDAC tumors (15/17 vs. 14/17). The concordance for MUC4 expression in primary tumors and corresponding lymph node metastases was 82%. In two cases, the primary tumor was MUC4-positive and the lymph node metastases were negative, while in one patient with a MUC4-negative primary tumor, the lymph node metastasis was positive. The distribution of H-score for expression of MUC4 significantly correlated (r = 0.615; p = 0.009) between primary tumors and paired metastatic lesions. Conclusions: MUC4 was observed in both primary and matched metastatic tumors with a high level of concordance, suggesting that MUC4 expression is retained following PDAC metastasis.
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| 5. |
- Bauden, Monika, et al.
(författare)
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Novel anti-adhesive barrier Biobarrier reduces growth of colon cancer cells.
- 2014
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 191:1, s. 196-202
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Tidskriftsartikel (refereegranskat)abstract
- Postoperative peritoneal carcinomatosis together with adhesion formation are considered as two major clinical complications after resection of malignant abdominal tumors, jeopardizing the beneficial effect of the curative surgery. Biobarrier is a novel anti-adhesive barrier fulfilling the criteria for a good adhesion preventive agent, possessing biochemical properties that may enable it to function as a dual efficient device, reducing both adhesion and tumor development. This study aims to evaluate the effect of novel anti-adhesive device Biobarrier on intra-abdominal tumor progression.
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| 6. |
- Isaksson, Karolin, et al.
(författare)
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In vivo toxicity and biodistribution of intraperitoneal and intravenous poly-L-lysine and poly-L-lysine/poly-L-glutamate in rats.
- 2014
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Ingår i: Journal of Materials Science: Materials in Medicine. - : Springer Science and Business Media LLC. - 1573-4838 .- 0957-4530. ; 25:5, s. 1293-1299
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Tidskriftsartikel (refereegranskat)abstract
- The combination of two differently charged polypeptides, poly-L-lysine (PL) and poly-L-glutamate (PG), has shown excellent postsurgical antiadhesive properties. However, the high molecular, positively charged PL is toxic in high doses, proposed as lysis of red blood cells. This study aims to elucidate the in vivo toxicity and biodistribution of PL and complex bound PLPG comparing intravenous and intraperitoneal administration. Fifty-six Sprague-Dawley rats were used in a model with repeated blood samples within 30 min examining blood gases and blood smears. Similarly, FITC labelled PL were used to track bio distribution and clearance of PL, given as single dose and complex bound to PG after intravenous and intraperitoneal administration. Tissue for histology and immunohistochemistry was collected. Blood gases and blood smears as well as histology points to a toxic effect of high dose PL given intravenously but not after intraperitoneal administration. The toxic effect is exerted through endothelial disruption and subsequent bleeding in the lungs, provoking sanguineous lung edema. FITC-labelled PL experiments reveal a rapid clearance with differences between routes and complex binding. This study advocates a new theory of the toxic effects in vivo of high molecular PL. PLPG complex is safe to use as antiadhesive prevention based on this toxicity study given that PL is always intraperitoneally administered in combination with PG and that the dose is adequate.
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| 7. |
- Åkerberg, Daniel, et al.
(författare)
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Effects of Polylysine and Polyglutamate on Inflammation and the Normal Process of Peritoneal Healing After Surgery
- 2012
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Ingår i: Journal of Tissue Science & Engineering. - : OMICS Publishing Group. - 2157-7552. ; 3:2, s. 1-7
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Introduction: Intraperitoneal adhesions are common after abdominal surgery and may lead to serious clinical complications. Previous studies have investigated the possible effects of the polypeptides poly-L-lysine (αPL) and poly-L-glutamate (PG) forming a polymer complex that prohibits local peritoneal adhesions after surgery. The aim of this study was to examine whether the normal process of peritoneal healing was affected by PL/PG polymer matrix. Material and methods: Male rats (Sprague Dawley) (n=84) underwent abdominal wall surgery and suturing. Rats were randomized in groups according to evaluation time (2, 4, 6, 8, 24 hours and 7 days) with corresponding control groups. Controls received saline (0.9%) and the experimental groups received PL/PG on the surgery site. tPA, PAI-1, IL-6 and active TGFb1 were analyzed at given time points postoperatively in peritoneal lavage. Adhesions were evaluated after seven days. Significant differences were considered to be p<0.05. Results: At a few individual time points small differences were seen between the groups (control and experiment) comparing levels of tPA, PAI-1, IL-6 and active TGFb1. When comparing levels of substances from all time points no statistical differences were seen between the groups as a total. Adhesions were significantly decreased on day 7, p=0.002. Conclusion: Despite significant reduction in adhesions PL/PG administered intraperitoneally as an anti-adhesion agent locally on surgically traumatized area does not seem to affect the normal process of peritoneal healing.
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| 8. |
- Åkerberg, Daniel, et al.
(författare)
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Prevention of Adhesions by PL/PG after Adhesiolysis
- 2012
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Ingår i: Journal of Tissue Science & Engineering. - : OMICS Publishing Group. - 2157-7552. ; 3:4
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Background: Previous studies of differently charged polypeptides, Poly-L-lysine (PL) and Poly-L-Glutamate (PG) have shown promising results, reducing postoperative adhesions. This study aimed to investigate the possible anti adhesion effect of those combined polypeptides, after adhesiolys. The concentration of tPA, PAI-1 and active TGFb1 in biopsies from adhesions, unharmed peritoneum before and after adhesiolysis, was also investigated. Materials and methods: A total of 24 male rats were divided in three groups A (N=8), B (N=8) and C (N=8). All rats underwent primary adhesion creating surgery at day 0, and adhesiolysis at day 7. Adhesions were evaluated at day 7 and 14, where group B received PL/PG after surgery at day 0 and after adhesiolysis at day 7, and group C received PL/PG after adhesiolysis at day 7. Tissue plasminogen activator (tPA), Plasminogen activator inhibitor 1(PAI-1) and active transforming growth factor beta 1(TGF-β1) were collected from biopsies of adhesions and normal peritoneum at day 0, 7 and 14. Results: Significant reduction of adhesions p<0.05 was seen in group B at day 7 after primary surgery, and at day 14 after adhesiolysis. Significantly p<0.05 reduction of adhesions was seen at day 14 after adhesiolysis in group C. Some variations were seen in tPA, PAI-1 and active TGFb1. Conclusions: PL/PG may be used to prevent adhesion formation after adhesiolysis. The process of fibrinolysis and fibrosis was not affected, after PL/PG prophylaxis and adhesiolysis.
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| 9. |
- Åkerberg, Daniel, et al.
(författare)
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Prevention of pleural adhesions by bioactive polypeptides - a pilot study.
- 2013
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Ingår i: International Journal of Medical Sciences. - : Ivyspring International Publisher. - 1449-1907. ; 10:12, s. 1720-1726
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Postoperative pleural adhesions lead to major problems in repeated thoracic surgery. To date, no antiadhesive product has been proven clinically effective. Previous studies of differently charged polypeptides, poly-L-lysine (PL) and poly-L-glutamate (PG) have shown promising results reducing postoperative abdominal adhesions in experimental settings. This pilot study examined the possible pleural adhesion prevention by using the PL+PG concept after pleural surgery and its possible effect on key parameters; plasmin activator inhibitor-1 (PAI-1) and tissue growth factor beta 1 (TGFb) in the fibrinolytic process. Methods: A total of 22 male rats were used in the study, one control group (n=10) and one experimental group (n=12). All animals underwent primary pleural surgery, the controls receiving saline in the pleural cavity and the experimental group the PL+PG solution administered by spray. The animals were evaluated on day 7. Macroscopic appearance of adhesions was evaluated by a scoring system. Histology slides of the adhesions and pleural biopsies for evaluation of PAI-1 and TGFb1 were taken on day 7. Results: A significant reduction of adhesions in the PL+PG group (p<0.05) was noted at day 7 both regarding the length and severity of adhesions. There were no significant differences in the concentration of PAI-1 and TGFb1 when comparing the two groups. Conclusions: PL+PG may be used to prevent pleural adhesions. The process of fibrinolysis, and fibrosis was though not affected after PLPG administration.
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| 10. |
- Åkerberg, Daniel, et al.
(författare)
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The influence on abdominal adhesions and inflammation in rabbits after exposure to differently charged polypeptides
- 2012
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Ingår i: Journal of Biomedical Science and Engineering. - : Scientific Research Publishing, Inc.. - 1937-6871 .- 1937-688X. ; 5, s. 432-438
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Background: Abdominal adhesions develop on da- maged peritoneal surfaces and constitute a significant health related problem. Previous animal studies have shown promising anti-adhesive effects when adminis- tering the polycation α-poly-L-lysine (αPL) and the polyanion poly-L-glutamate (PG) together. The ob- jective of the study was to examine the effect of these differently charged polypeptides when administered by spraying and to evaluate any possible effect on fibrinolysis, fibrosis and inflammation. Methods: Rab- bits were treated with PLPG after cecal abrasive surgery and analysis from peritoneal biopsies of ac- tive tPa/PAI-1 complex and from peritoneal fluid of IL-6 and active TGFb1 at day 0, 1, 4 and 10 were measured after surgery. Histological specimens were analyzed on day 10 regarding inflammation and fib- rosis. Peritoneal adhesions were evaluated by adhe- sion score. All values were compared to the control group (NaCl). Results: PLPG-treated rabbits had a significant diminished adhesion score on day 10 as compared to the control group (p < 0.005). Signifi- cantly reduced collagen depositions on the perito- neum were seen in the PLPG group when evaluating the histological specimens (p < 0.05). No significant differences between the experimental and control groups were seen in peritoneal fluid when analyzing for active protein levels. Conclusion: This is the first study to investigate the effect on key parameters in adhesion formation as well as the preventive effect of the PLPG complex on abdominal adhesions in rabbits and also the first study where administration by spraying the polypeptides was used. PLPG was non- toxic in this setting and without significant differences in adhesion formation parameters and a significant reduction in adhesions was observed. This was veri- fied both macroscopically and histologically.
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