| 1. |
- Changhui, Yu, et al.
(author)
-
Inhibition of Ras signalling reduces neutrophil infiltration and tissue damage in severe acute pancreatitis.
- 2015
-
In: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 746, s. 245-251
-
Journal article (peer-reviewed)abstract
- Neutrophil recruitment is known to be a rate-limiting step in mediating tissue injury in severe acute pancreatitis (AP). However, the signalling mechanisms controlling inflammation and organ damage in AP remain elusive. Herein, we examined the role of Ras signalling in AP. Male C57BL/6 mice were treated with a Ras inhibitor (farnesylthiosalicylic acid, FTS) before infusion of taurocholate into the pancreatic duct. Pancreatic and lung tissues as well as blood were collected 24h after pancreatitis induction. Pretreatment with FTS decreased serum amylase levels by 82% and significantly attenuated acinar cell necrosis, tissue haemorrhage and oedema formation in taurocholate-induced pancreatitis. Inhibition of Ras signalling reduced myeloperoxidase (MPO) levels in the inflamed pancreas by 42%. In addition, administration of FTS decreased pancreatic levels of CXC chemokines as well as circulating levels of interleukin-6 and high-mobility group box 1 in animals exposed to taurocholate. Moreover, treatment with FTS reduced taurocholate-induced MPO levels in the lung. Inhibition of Ras signalling had no effect on neutrophil expression of Mac-1 in mice with pancreatitis. Moreover, FTS had no direct impact on trypsin activation in isolated pancreatic acinar cells. These results indicate that Ras signalling controls CXC chemokine formation, neutrophil recruitment and tissue injury in severe AP. Thus, our findings highlight a new signalling mechanism regulating neutrophil recruitment in the pancreas and suggest that inhibition of Ras signalling might be a useful strategy to attenuate local and systemic inflammation in severe AP.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Hwaiz, Rundk, et al.
(author)
-
Rac1-dependent secretion of platelet-derived CCL5 regulates neutrophil recruitment via activation of alveolar macrophages in septic lung injury.
- 2015
-
In: Journal of Leukocyte Biology. - 1938-3673. ; 97:5, s. 975-984
-
Journal article (peer-reviewed)abstract
- Accumulating evidence suggest that platelets play an important role in regulating neutrophil recruitment in septic lung injury. Herein, we hypothesized that platelet-derived CCL5 might facilitate sepsis-induced neutrophil accumulation in the lung. Abdominal sepsis was induced by CLP in C57BL/6 mice. CLP increased plasma levels of CCL5. Platelet depletion and treatment with the Rac1 inhibitor NSC23766 markedly reduced CCL5 in the plasma of septic mice. Moreover, Rac1 inhibition completely inhibited proteasePAR4-induced secretion of CCL5 in isolated platelets. Immunoneutralization of CCL5 decreased CLP-induced neutrophil infiltration, edema formation, and tissue injury in the lung. However, inhibition of CCL5 function had no effect on CLP-induced expression of Mac-1 on neutrophils. The blocking of CCL5 decreased plasma and lung levels of CXCL1 and CXCL2 in septic animals. CCL5 had no effect on neutrophil chemotaxis in vitro, suggesting an indirect effect of CCL5 on neutrophil recruitment. Intratracheal challenge with CCL5 increased accumulation of neutrophils and formation of CXCL2 in the lung. Administration of the CXCR2 antagonist SB225002 abolished CCL5-induced pulmonary recruitment of neutrophils. Isolated alveolar macrophages expressed significant levels of the CCL5 receptors CCR1 and CCR5. In addition, CCL5 triggered significant secretion of CXCL2 from isolated alveolar macrophages. Notably, intratracheal administration of clodronate not only depleted mice of alveolar macrophages but also abolished CCL5-induced formation of CXCL2 in the lung. Taken together, our findings suggest that Rac1 regulates platelet secretion of CCL5 and that CCL5 is a potent inducer of neutrophil recruitment in septic lung injury via formation of CXCL2 in alveolar macrophages.
|
|
| 5. |
|
|
| 6. |
- Merza, Mohammed, et al.
(author)
-
Neutrophil Extracellular Traps Induce Trypsin Activation, Inflammation, and Tissue Damage in Mice with Severe Acute Pancreatitis.
- 2015
-
In: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 149:7, s. 1920-1920
-
Journal article (peer-reviewed)abstract
- Neutrophils are involved in development of acute pancreatitis (AP), but it is not clear how neutrophil-induced tissue damage is regulated. In addition to secreting antimicrobial compounds, activated neutrophils eliminate invading microorganisms by expelling nuclear DNA and histones to form extracellular web-like structures called neutrophil extracellular traps (NETs). However, NETs have been reported contribute to organ dysfunction in patients with infectious diseases. We investigated whether NETs contribute to development of AP in mice.
|
|
| 7. |
- Nemeth, Artur, et al.
(author)
-
Use of patency capsule in patients with established Crohn's disease.
- 2015
-
In: Endoscopy. - : Georg Thieme Verlag KG. - 1438-8812 .- 0013-726X.
-
Journal article (peer-reviewed)abstract
- Background and study aims: Video capsule endoscopy (VCE) is invaluable in the diagnosis of small-bowel pathology. Capsule retention is a major concern in patients with Crohn's disease. The patency capsule was designed to evaluate small-bowel patency before VCE. However, the actual benefit of the patency capsule test in Crohn's disease remains unclear. The aim of this study was to evaluate the clinical impact of patency capsule use on the risk of video capsule retention in patients with established Crohn's disease. Patients and methods: This was a retrospective, multicenter study of patients with established Crohn's disease who underwent VCE for clinical need. The utilization strategy for the patency capsule was classified as selective (only in patients with obstructive symptoms, history of intestinal obstruction or surgery, or per treating physician's request) or nonselective (all patients with Crohn's disease). The main outcome was video capsule retention in the entire cohort and within each utilization strategy. Results: A total of 406 patients who were referred for VCE were included in the study. VCE was performed in 132 /406 patients (32.5 %) without a prior patency capsule test. The patency capsule test was performed in 274 /406 patients (67.5 %) and was negative in 193 patients. Overall, VCE was performed in 343 patients and was retained in the small bowel in 8 (2.3 %). In this cohort, the risk of video capsule retention in the small bowel was 1.5 % without use of a prior patency capsule and 2.1 % after a negative patency test (P = 0.9). A total of 18 patients underwent VCE after a positive patency capsule test, with a retention rate of 11.1 % (P = 0.01). Patency capsule administration strategy (selective vs. nonselective) was not associated with the risk of video capsule retention. Conclusions: Capsule retention is a rare event in patients with established Crohn's disease undergoing VCE. The risk of video capsule retention was not reduced by the nonselective use of the patency capsule. Furthermore, VCE after a positive patency capsule test in patients with Crohn's disease was associated with a high risk of video capsule retention.
|
|
| 8. |
- Puegge, Johanna, et al.
(author)
-
Adhesive Mechanisms of Histone-Induced Neutrophil-Endothelium Interactions in the Muscle Microcirculation.
- 2015
-
In: European Surgical Research. - : S. Karger AG. - 0014-312X .- 1421-9921. ; 56:1-2, s. 19-31
-
Journal article (peer-reviewed)abstract
- Extracellular histones released during cell damage have the capacity to cause tissue injury associated with increased leukocyte accumulation. However, the molecular mechanisms regulating histone-induced leukocyte recruitment remain elusive. The objective of this study was to examine the role of adhesion molecules in histone-dependent leukocyte accumulation by use of intravital microscopy of the mouse cremaster microcirculation.
|
|
| 9. |
- Rönnow, Carl-Fredrik, et al.
(author)
-
A new needle holder facilitating palm grip suturing.
- 2015
-
In: European Surgical Research. - : S. Karger AG. - 0014-312X .- 1421-9921. ; 54:1-2, s. 55-63
-
Journal article (peer-reviewed)abstract
- The finger grip and the palm grip are the most common needle holder grips for hand suturing in surgery. The major advantages of the palm grip are an increased versatility and the possibility to apply controlled force. However, there is a risk for a potential loss of precision and uncontrolled movement of the needle when disengaging the ratchet mechanism of the palmed instrument. The purpose of this study was to develop a new needle holder, referred to as the Frimand needle holder (FNH), and evaluate surgeons' perception of it. It was designed to overcome the above-mentioned disadvantages, hence facilitating palm and finger grip suturing. Moreover, we evaluated suture precision and attitudes related to the use of the finger grip and the palm grip.
|
|
| 10. |
- Thorlacius, Henrik, et al.
(author)
-
Sågtandande polyper en dold men vanlig orsak till kolorektal cancer : Serrated polyps is a hidden but common cause of colorectal cancer
- 2015
-
In: Läkartidningen. - 0023-7205. ; 112:34-35, s. 1401-1405
-
Journal article (other academic/artistic)abstract
- Konceptet att sågtandande polyper kan leda till kolorektal cancer är relativt nytt. Sågtandade polyper orsakar upp till en tredjedel av all sporadisk kolorektal cancer. Trots detta är kunskaperna om sågtandade polypers etiologi, incidens, prevalens och naturalförlopp ofullständiga. Sågtandade polyper är svåra att identifiera och ta bort endoskopiskt. Endoskopister och patologer måste ha kunskaper om sågtandade adenom för att effektivt kunna detektera, diagnostisera och ta bort dem som led i att minska antalet personer som drabbas av kolorektal cancer. The concept that serrated polyps can cause colorectal cancer is relatively new and not very well-known. Serrated polyps are difficult to identify and treat endoscopically. This together with the fact that premalignant serrated polyps are mainly located in the proximal colon might help explain why colonoscopy is less effective against right-sided compared to left-sided colorectal cancers and why interval cancers usually appear in the proximal colon. In fact, serrated polyps may cause up to one third of all sporadic colorectal cancers. In spite of this, the aetiology, incidence, prevalence and natural history of serrated polyps remains elusive. Endoscopists and pathologists must have a good understanding of serrated polyps in order to effectively diagnose, treat and follow up these lesions. This review focuses on the pathophysiology, types, work-up, treatment and follow-up of serrated polyps in the colon and rectum.
|
|
