Jueves 28 de Febrero de 2008; 09:00 hrs.

 

Cannabinoids Reduce Markers of Inflammation and Fibrosis in Pancreatic Stellate Cells

 

Michalski CW, Maier M, Erkan M, Sauliunaite D, Bergmann F, et al. (2008) Cannabinoids Reduce Markers of Inflammation and Fibrosis in Pancreatic Stellate Cells. PLoS ONE 3(2): e1701 doi:10.1371/journal.pone.0001701

Background

While cannabinoids have been shown to ameliorate liver fibrosis, their effects in chronic pancreatitis and on pancreatic stellate cells (PSC) are unknown.

Methodology/Principal Findings

The activity of the endocannabinoid system was evaluated in human chronic pancreatitis (CP) tissues. In vitro, effects of blockade and activation of cannabinoid receptors on pancreatic stellate cells were characterized. In CP, cannabinoid receptors were detected predominantly in areas with inflammatory changes, stellate cells and nerves. Levels of endocannabinoids were decreased compared with normal pancreas. Cannabinoid-receptor-1 antagonism effectuated a small PSC phenotype and a trend toward increased invasiveness. Activation of cannabinoid receptors, however, induced de-activation of PSC and dose-dependently inhibited growth and decreased IL-6 and MCP-1 secretion as well as fibronectin, collagen1 and alphaSMA levels. De-activation of PSC was partially reversible using a combination of cannabinoid-receptor-1 and -2 antagonists. Concomitantly, cannabinoid receptor activation specifically decreased invasiveness of PSC, MMP-2 secretion and led to changes in PSC phenotype accompanied by a reduction of intracellular stress fibres.

Conclusions/Significance

Augmentation of the endocannabinoid system via exogenously administered cannabinoid receptor agonists specifically induces a functionally and metabolically quiescent pancreatic stellate cell phenotype and may thus constitute an option to treat inflammation and fibrosis in chronic pancreatitis.....Más..

 

Lunes 25 de Febrero de 2008; 09 50hrs.

Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial

 

• Marc GH Besselink, Hjalmar C van Santvoort, Erik Buskens et al. The Lancet Volume 371, Issue 9613, 23 February 2008-29 February 2008, Pages 651-659
  
  

• Background

  Infectious complications and associated mortality are a major concern in acute pancreatitis. Enteral administration of probiotics could prevent infectious complications, but convincing evidence is scarce. Our aim was to assess the effects of probiotic prophylaxis in patients with predicted severe acute pancreatitis.

  Methods

  In this multicentre randomised, double-blind, placebo-controlled trial, 298 patients with predicted severe acute pancreatitis (Acute Physiology and Chronic Health Evaluation [APACHE II] score ≥8, Imrie score ≥3, or C-reactive protein >150 mg/L) were randomly assigned within 72 h of onset of symptoms to receive a multispecies probiotic preparation (n=153) or placebo (n=145), administered enterally twice daily for 28 days. The primary endpoint was the composite of infectious complications—ie, infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis, or infected ascites—during admission and 90-day follow-up. Analyses were by intention to treat. This study is registered, number ISRCTN38327949.

  Findings

  One person in each group was excluded from analyses because of incorrect diagnoses of pancreatitis; thus, 152 individuals in the probiotics group and 144 in the placebo group were analysed. Groups were much the same at baseline in terms of patients' characteristics and disease severity. Infectious complications occurred in 46 (30%) patients in the probiotics group and 41 (28%) of those in the placebo group (relative risk 1·06, 95% CI 0·75–1·51). 24 (16%) patients in the probiotics group died, compared with nine (6%) in the placebo group (relative risk 2·53, 95% CI 1·22–5·25). Nine patients in the probiotics group developed bowel ischaemia (eight with fatal outcome), compared with none in the placebo group (p=0·004).

  Interpretation

  In patients with predicted severe acute pancreatitis, probiotic prophylaxis with this combination of probiotic strains did not reduce the risk of infectious complications and was associated with an increased risk of mortality. Probiotic prophylaxis should therefore not be administered in this category of patients. ...Más..

 

Martes 12 de Febrero de 2008; 10:05 hrs.

Cholesterol in islet dysfunction and type 2 diabetes

 

• Liam R. Brunham, Janine K. Kruit, C. Bruce Verchere and Michael R. Hayden. J. Clin. Invest. 118(2): 403-408 (2008). doi:10.1172/JCI33296.

• Type 2 diabetes (T2D) frequently occurs in the context of abnormalities of plasma lipoproteins. However, a role for elevated levels of plasma cholesterol in the pathogenesis of this disease is not well established. Recent evidence suggests that alterations of plasma and islet cholesterol levels may contribute to islet dysfunction and loss of insulin secretion. A number of genes involved in lipid metabolism have been implicated in T2D. Recently an important role for ABCA1, a cellular cholesterol transporter, has emerged in regulating cholesterol homeostasis and insulin secretion in pancreatic β cells. Here we review the impact of cholesterol metabolism on islet function and its potential relationship to T2D.

  Type 2 diabetes (T2D) is characterized by an inability of the endocrine pancreas to secrete sufficient insulin to meet the metabolic demands associated with insulin resistance and obesity. β cell dysfunction is a key element in the pathogenesis of this disorder. A reduction in glucose-stimulated insulin secretion is a virtually uniform finding among patients with....Más.