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    Abdominal paracentesis drainage ameliorates severe acute pancreatitis in rats by regulating the polarization of peritoneal macrophages
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    Abstract:
    To investigate the role of peritoneal macrophage (PM) polarization in the therapeutic effect of abdominal paracentesis drainage (APD) on severe acute pancreatitis (SAP).SAP was induced by 5% Na-taurocholate retrograde injection in Sprague-Dawley rats. APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after the induction of SAP. To verify the effect of APD on macrophages, PMs were isolated and cultured in an environment, with the peritoneal inflammatory environment simulated by the addition of peritoneal lavage in complete RPMI 1640 medium. Hematoxylin and eosin staining was performed. The levels of pancreatitis biomarkers amylase and lipase as well as the levels of inflammatory mediators in the blood and peritoneal lavage were determined. The polarization phenotypes of the PMs were identified by detecting the marker expression of M1/M2 macrophages via flow cytometry, qPCR and immunohistochemical staining. The protein expression in macrophages that had infiltrated the pancreas was determined by Western blot.APD treatment significantly reduced the histopathological scores and levels of amylase, lipase, tumor necrosis factor-α and interleukin (IL)-1β, indicating that APD ameliorates the severity of SAP. Importantly, we found that APD treatment polarized PMs towards the M2 phenotype, as evidenced by the reduced number of M1 macrophages and the reduced levels of pro-inflammatory mediators, such as IL-1β and L-selectin, as well as the increased number of M2 macrophages and increased levels of anti-inflammatory mediators, such as IL-4 and IL-10. Furthermore, in an in vitro study wherein peritoneal lavage from the APD group was added to the cultured PMs to simulate the peritoneal inflammatory environment, PMs also exhibited a dominant M2 phenotype, resulting in a significantly lower level of inflammation. Finally, APD treatment increased the proportion of M2 macrophages and upregulated the expression of the anti-inflammatory protein Arg-1 in the pancreas of SAP model rats.These findings suggest that APD treatment exerts anti-inflammatory effects by regulating the M2 polarization of PMs, providing novel insights into the mechanism underlying its therapeutic effect.
    Keywords:
    Peritoneal fluid
    Peritoneal cavity
    Macrophage polarization
    Objective To investigate the correlation between intestinal endotoxemia(IETM) and pathological changes of pancreas of severe acute pancreatitis.Methods There were 40 Wistar rats weighing(260±20)g with no limitation in sexe.They were divide into sham operation(SO) group (n=8) and severe acute pancreatitis(SAP) model group(n=32) randomly.The latter was divided into 3-h group,12-h group,24-h group and 36-h group randomly(each,n=8).The changes of plasma endotoxin and the score of pancreatic pathology was observed.Results There was a significant increase of plasma endotoxin(ET) and serum amylase(AMY) contents 3 h after the modeling.Compared with SO group,they had statistical significance(P0.01) 3 h after model establishment,indicating the formation of IETM,and hereafter slowly ascending tendency.With increasing of IETM contents,pathological changes of pancreas were aggravating.Conclusion IETM aggravates pathological changes of pancreas.
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    Epidemiological studies show that smokers are at a significantly higher (70%) risk of getting affected by chronic pancreatitis and tumours of pancreas than non-smokers. The aim of the study was to assess the effect of cigarette smoking on the expression of gene p53 in pancreas by defining immunohistochemical localization of p53 protein in tissue specimens of the pancreases derived from healthy persons and smoking and non-smoking patients with diagnosed chronic pancreatitis (CP). Patients underwent surgery in which tissue material was collected. Immunohistochemical localization of 53 protein in paraffin tissue specimens of the pancreas was performed using the LSAB2-HRP visual test (DAKO K0673) with monoclonal p53 protein (DAKO N1581) antibodies. Exposure to tobacco smoke was assessed by determining cotinine in the patients' serum using the ELISA method. The study revealed a expression of p53 protein in smoking CP patients. In non-smoking patients and healthy persons wasn't showed expression of protein. Smoking patients above the twenty cigarettes for day showed significantly higher expression of p53 protein in the pancreas compared to smoking patients less. Cigarette smoking increases the expression p53 protein in pancreas of smoking patients with chronic pancreatitis. Impairment of the gene p53 in pancreas is frequently manifested by complications in pancreatitis resulting among others from long-term smoking, and conducted by tumour proliferation.
    Cotinine
    Citations (3)
    Peritoneal lavage was developed as a simple method to evacuate the ascitic fluid associated with pancreatitis. Although a number of studies demonstrated its efficacy in improvement of clinical manifestations, a meta-analysis of randomized control studies could not reveal its effectiveness on mortality or morbidity in severe acute pancreatitis. However, it has been well established that the ascitic fluid with pancreatitis is extremely toxic and to induce organ damage due to apoptotic cell death. Particularly, we have recently found that the ascitic fluid with pancreatitis can induce bacterial translocation due to the increase of gut permeability. Therapeutic strategy of peritoneal lavage, i.e. evacuation of toxic substances from peritoneal cavity, should be reevaluated to achieve further improvement of treatment result of severe acute pancreatitis.
    Peritoneal cavity
    Peritoneal fluid
    Ascitic fluid
    Citations (3)
    An analysis of 98 cases of acute postoperative pancreatitis has been made. The development of acute postoperative pancreatitis was found to be associated with the appearance of fat tissue necrosis under the influence of the activated enzymes of the pancreas The involvement of exocrinous and endocrinous structures of the pancreas into the inflammatory process was developing with progressing of the disease. Postoperative purulent pancreatitis was caused by the secondary infection of the pancreas and the pancreatic fat tissue.
    Fat necrosis
    Citations (0)
    OBJECTIVE To investigate whether measuring pancreas volume with abdominal tomography in patients with severe abdominal pain can predict acute pancreatitis. METHODS The case-control study was conducted at Adnan Menderes University from January 1, 2015, to January 1, 2017, and comprised patients who were diagnosed with acute pancreatitis. Pancreas volume measurements of patients and control group were made with Telemed Ekinoks software using freehand technique. Presence of a correlation between pancreas volume and pancreatitis was found in patients aged <57 years and a cut-off value was calculated for pancreatitis in this particular patient group. RESULTS Of the 183 subjects, 132(72%) were patients with a mean age of 59.6±16.5 years, and 51(28%) were controls with a mean age of 55.8±18.6 years (p=0.170). The difference between the groups in terms of pancreas volume was significant (p<0.001). There was a negative correlation between age and pancreas volume among the patients (p<0.001), the correlation was not significant among the controls (p=0.898). Among the subjects aged <57 years, the cut-off value was calculated at 95.055, and sensitivity to pancreas volume was 70.91% while specificity was 82.14%. Positive predictive value was 88.6%. CONCLUSIONS High pancreas volume with pancreatitis was observed in patients aged <57 years.
    Citations (2)
    Acute necrohemorrhagic pancreatitis was induced in rabbits by multiple interstitial trypsin injections in the body of the pancreas. The time course of regeneration was followed for 12 weeks. Chronic pancreatitis-like changes persisted for 4 weeks in all experimental animals, and the recovery was complete after 12 weeks. Reversible fibrosis and regressive acinar changes (“tubular complexes”) were most severe in the region of the trypsin injections. Three-dimensional reconstruction of the pancreas showed an anastomosing tubular arrangement in the areas of “pseudochronic pancreatitis” but not in the normal pancreas.
    Pancreatic Disease
    Severe acute pancreatitis is often complicated by intraperitoneal infection, resulting in multiple organ failure (MOF). It is known to elevate serum tumor necrosis factor (TNF-alpha) in patients with sepsis and/or MOF. In order to study the role of TNF-alpha in the aggravation of acute pancreatitis, we investigated TNF-alpha production by peritoneal macrophages in acute pancreatitis rat using the cerulein-induced pancreatitis model. TNF-alpha production by isolated peritoneal macrophages following lipopolysaccharide (LPS) stimulation was significantly increased in pancreatitis rats as compared with nonpancreatitis control rats (p < 0.001). Serum TNF-alpha activity was elevated following intraperitoneal administration of LPS as the septic challenge both in pancreatitis rats and in control rats, being significantly higher in the former (p < 0.05). Histological findings and liver function tests revealed that LPS induced more severe liver damage in pancreatitis rats than in control rats within 24 h after LPS administration. These results indicate that increased TNF-alpha production by peritoneal macrophages in acute pancreatitis augmented LPS-induced liver injury and suggest the possibility that TNF-alpha may play a role in the development of MOF during acute pancreatitis complicated by intraabdominal sepsis.
    Ceruletide
    Pancreatic Disease
    Intraperitoneal injection
    Citations (51)
    Pathogenesis
    Pancreatic elastase
    Pancreatic enzymes
    Exocrine pancreas
    Proteolytic enzymes
    ACCUMULATION of fluid in the peritoneal cavity may occur in a variety of pancreatic lesions. In approximately 10% of patients with carcinoma of the pancreas, for example, ascites may develop. This usually indicates widespread peritoneal metastases. Some accumulation of peritoneal fluid is common in patients who die from severe forms of chronic pancreatitis. In general, however, ascites is unusual with reversible, chronic pancreatic disease. A pseudocyst of the pancreas is seldom considered in the differential diagnosis of massive ascites. Although case reports have occurred in the literature, this association has received no attention in the surgical literature. In fact, a few years ago a review of 150 collected cases disclosed only one patient in whom ascites was mentioned as a clinical feature.1The authors have observed four patients in whom ascites was associated with pseudocysts of the pancreas and in whom the association appears to be specifically related, and
    Peritoneal cavity
    Pancreatic pseudocyst
    Pancreatic Disease
    Peritoneal fluid