Gastroparesis in the intensive care unit.

Gastroparesis is a common problem in the intensive care unit. Impaired gastric motility in critically ill patients is associated with an increased risk of enteral feeding intolerance, gastric bacterial colonization, pulmonary aspiration and progressive malnutrition leading to adverse outcomes. It is estimated that at least 60% of intensive care patients are affected by some form of gastrointestinal tract failure and that in 30% of critically ill patients in whom enteral feeding is attempted the feeding route needs to be modified because of feeding intolerance. The article highlights the physiology of normal gastric motor function and mechanisms of abnormal gastric motility as well as the current approach to detecting and treating feeding intolerance in intensive care.

The Role of Fecal Microbiota Transplantation in the Treatment of Inflammatory Bowel Disease.

The exact pathogenesis of inflammatory bowel disease (IBD) is still not completely understood. It is hypothesized that a genetic predisposition leads to an exaggerated immune response to an environmental trigger, leading to uncontrolled inflammation. As there is no known causative treatment, current management strategies for inflammatory bowel disease focus on correcting the excessive immune response to environmental (including microbial) triggers. In recent years, there has been growing interest in new avenues of treatment, including targeting the microbial environment itself. Fecal microbiota transplantation (FMT) is a novel treatment modality showing promising results in early studies. The article discusses the rationale for the use of FMT in inflammatory bowel disease and the yet-unresolved questions surrounding its optimal use in practice.

High levels of reactive oxygen species in pancreatic necrotic fluid of patients with walled-off pancreatic necrosis.

INTRODUCTION: Walled-off pancreatic necrosis (WOPN) is a life-threatening, late complication of acute pancreatitis, in which a fluid collection containing necrotic material is formed. Infection of the fluid collection significantly increases the mortality of patients with WOPN. AIM: To examine the levels of oxidative stress markers in the pancreatic necrotic fluid (PNF) and serum of patients with sterile and infected WOPN. MATERIAL AND METHODS: Thirty-three adult patients with sterile WOPN and 14 with infected WOPN, as well as 31 patients with mild AP, were included in this study. Concentrations of oxidative stress markers (8-isoprostane, protein carbonyl groups, and 8-hydroxyguanine) were measured in the PNF and serum of patients with sterile and infected WOPN. RESULTS: High concentrations of all measured oxidative stress markers in PNF, but not in serum, were detected in patients with WOPN. Additionally, oxidative stress markers in PNF were significantly increased in patients with infected as compared to sterile WOPN. The serum high sensitive C-reactive protein (hsCRP) concentrations showed the highest correlation with PNF oxidative stress marker levels. Receiver operating characteristics (ROC) curve analysis confirmed that serum hsCRP could be a good predictor of WOPN infection. CONCLUSIONS: Oxidative stress is associated with WOPN development; infection of PNF worsens the course of WOPN, possibly via increased production of reactive oxygen species; and serum hsCRP concentrations seem to be a good, noninvasive indicator of PNF infection.

The role of chemerin in human disease.

Adipose tissue is not merely a storage depot of triacylglycerols but also a major endocrine organ. Its cells, including adipocytes, synthesize and secrete a range of biologically active molecules termed adipokines. Adipokines that display the properties of cytokines are often called adipocytokines. In recent years there has been increasing interest in a new adipokine called chemerin. Chemerin is a protein synthesized mostly by the adipose tissue and the liver as inactive pre­pro­chemerin. After the intracellular hydrolytic cutting off of the 20­amino­acid N­terminal polypeptide, it is secreted into the bloodstream as inactive pro­chemerin. Biologically active chemerin is then derived from pro­chemerin after cleavage of the C­terminal fragment by serum proteases involved in inflammation, coagulation and fibrinolysis. Proteolytic cleavage leads to formation of several chemerin­derived peptides, both biologically active (often with opposing functions) and inactive. Within the last decade, there has been a growing number of publications regarding the role of chemerin in human disease. It seems to be implicated in the inflammatory response, metabolic syndrome, cardiovascular disease and alimentary tract disorders. The article presents the most recent information on the role of chemerin in human disease, and specifically alimentary tract disorders. The available evidence suggests that chemerin is an important link between adipose tissue mass, metabolic processes, the immune system and inflammation, and therefore plays a major role in human pathophysiology.

Decreased serum platelet derived growth factor BB levels in acute and increased in chronic pancreatitis.

AIM: To examine circulating growth factor concentrations in patients with acute pancreatitis (AP) and chronic pancreatitis (CP), and walled-off pancreatic necrosis (WOPN). METHODS: Forty patients with mild AP, 40 patients with alcoholic CP, 33 patients with WOPN and 40 healthy subjects were examined. Serum concentrations of platelet derived growth factor BB (PDGF-BB), transforming growth factor ß-1 (TGFß-1), chemerin and high-mobility group box chromosomal protein 1 (HMBG1) were assayed by enzyme linked immunosorbent assay. RESULTS: Patients with mild AP and those with WOPN had significantly lower serum levels of PDGF-BB compared to healthy subjects (4.0 ± 0.61 ng/mL vs 6.2 ± 0.76 ng/mL, P = 0.027, and 1.60 ± 0.31 ng/mL vs 6.2 ± 0.76 ng/mL, P < 0.001, respectively), while CP was associated with higher serum levels of PDGF-BB (12 ± 1.3 ng/mL vs 6.2 ± 0.76 ng/mL, P < 0.001). Circulating TGFß-1 and chemerin levels were elevated in CP patients (57 ± 3.6 ng/mL vs 39 ± 3.6 ng/mL, P < 0.001 and 73 ± 7.2 ng/mL vs 48 ± 2.3 ng/mL, P < 0.001, respectively), but not in patients with AP and WOPN. No significant changes in serum HMBG1 levels were found either in patients with AP, WOPN or CP. CONCLUSION: The serum levels of some growth factors and cytokines differ significantly in AP, WOPN and CP. These data suggest that selected growth factors and cytokines may be considered as potential diagnostic biomarkers in patients with pancreatic diseases.

Increased serum chemerin concentration in patients with chronic pancreatitis.

BACKGROUND: Chemerin is a potent chemoattractant for chemokine-like receptor 1 expressing cells and is involved in inflammatory and immune processes that play an important role in chronic pancreatitis. AIM: To test the hypothesis that serum chemerin concentration may be affected in chronic pancreatitis patients and that chemerin can influence the course of chronic pancreatitis by increasing profibrotic cytokine production. METHODS: Serum concentrations of chemerin and the major cytokines involved in pancreatic fibrosis such as platelet-derived growth factor BB and transforming growth factor ß-1 were determined by ELISA in samples from 40 nondiabetic and 28 diabetic male patients with chronic pancreatitis of alcoholic origin and 40 age-matched healthy controls. RESULTS: Serum concentrations of chemerin were increased both in nondiabetic and diabetic chronic pancreatitis patients compared to controls. Moreover, in chronic pancreatitis patients a positive correlation was found between serum chemerin and platelet-derived growth factor BB as well as transforming growth factor ß-1 concentrations. CONCLUSIONS: The results indicate for the first time that: (a) chronic pancreatitis in humans is associated with an increased serum chemerin concentration and (b) serum chemerin concentration correlates with serum concentrations of the major profibrotic cytokines. Elevated level of chemerin, by stimulating macrophage infiltration of the pancreas, might lead to overproduction of platelet-derived growth factor BB and transforming growth factor ß-1 and, consequently, to pancreatic fibrosis.

Coordinated increase in serum platelet-derived growth factor-BB and transforming growth factor-ß1 in patients with chronic pancreatitis.

BACKGROUND: In vitro studies suggest that platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-ß1 (TGF-ß1) play an important role in pancreatic fibrosis. The aim of this study was to evaluate serum PDGF-BB and TGF-ß1 concentrations in patients with chronic pancreatitis (CP). METHODS: Forty male patients with a history of alcoholic CP and 35 age-matched healthy subjects were examined. Serum concentrations of PDGF-BB, TGF-ß1, laminin and hyaluronic acid were determined by ELISA assay. Additionally, we determined serum concentrations of PDGF-BB and TGF-ß1 in patients with functional dyspepsia, ulcerative colitis and Crohn's disease. RESULTS: Patients with advanced CP had significantly higher serum PDGF-BB and TGF-ß1 concentrations compared to control subjects. A strong positive correlation between serum PDGF-BB and TGF-ß1 concentrations was found in patients with CP. Serum laminin and hyaluronic acid were also elevated in patients with CP. No increase in serum PDGF-BB and TGF-ß1 concentrations was found in patients with functional dyspepsia, ulcerative colitis or Crohn's disease. CONCLUSION: The obtained results indicate for the first time that serum levels of PDGF-BB are elevated in patients with CP. However, ROC curve analysis suggests that PDGF-BB is not superior to laminin as a potential marker of advanced CP.

Decreased serum essential and aromatic amino acids in patients with chronic pancreatitis.

AIM: To investigate the influence of chronic pancreatitis (CP) on serum concentrations of amino acids. METHODS: Thirty-five male patients with alcoholic CP and 21 healthy male subjects were examined. Serum concentrations of amino acids were assayed by ion-pair high-performance liquid chromatography with mass detection. RESULTS: Serum glutamate concentration was increased in CP patients as compared to controls. In contrast, serum concentrations of glutamine, histidine, tyrosine, proline, tryptophan and threonine were significantly decreased in CP patients. A trend towards decreasing concentrations of serum lysine, alanine, methionine and valine as well as for total serum amino acids was observed. The sum of aromatic and the sum of essential amino acid concentrations were significantly lower in CP patients than in controls. CONCLUSION: CP leads to decreased serum concentrations of several amino acids, such as essential and aromatic serum amino acids, most likely due to decreased exocrine function.

Up-regulation of stearoyl-CoA desaturase 1 and elongase 6 genes expression in rat lipogenic tissues by chronic food restriction and chronic food restriction/refeeding.

Successful treatment of obesity and related diseases by chronic food restriction requires the understanding of the effect of such nutritional therapy on the expression of genes which have been implicated to be involved in some diseases associated with obesity. The purpose of this study was to examine the effect of chronic food restriction and chronic food restriction/refeeding on lipogenic enzymes, especially the expression of genes encoding the stearoyl-CoA desaturase 1 (Scd1) and elongase6 (Elovl6) in rat liver and adipose tissue. We found that both chronic food restriction and chronic food restriction/refeeding caused increased expression of the Scd1 and Elovl6 genes in both the liver and adipose tissue. The increase was more pronounced in case of chronic food restriction/refeeding (several-fold increase) than that in chronic food restriction alone (two to threefold increase). Essentially, similar results were obtained when the expression of fatty acid synthase, acetyl-CoA carboxylase, ATP-citrate lyase, and malic enzyme genes was studied. Moreover, we found that chronic food restriction and short-term fasting exert opposite effects on the expression of lipogenic enzymes genes. The increased expression of the genes encoding Scd1, Elovl6, and other key lipogenic enzymes may favor fat storage after chronic food restriction/refeeding and may be part of the molecular mechanism by which food restriction/refeeding increases body weight and enhances susceptibility to insulin resistance.