Intestinal barrier integrity and function in infants with cholestasis

Background/Aims: The safety of the human body is maintained by effective monitoring of the mucosal surface integrity and protection against potentially harmful compounds. This function of the gut called intestinal barrier function can be affected by cholestasis and the absence of bile in the intestinal lumen. We aimed to determine whether the gut barrier integrity is impaired in infants with cholestasis by evaluation of the intestinal fatty acid binding proteins (I-FABP) and ileal bile acid binding protein (I-BABP) as markers of intestinal epithelial cell damage and plasma D-lactate level as a marker of gut wall permeability.Methods: This case-control study included 53 infants with cholestasis and 29 controls. Serum levels of I-FABP, I-BABP, and D-lactate were measured in all subjects.Results: Both groups of patients with neonatal hepatitis and biliary atresia showed significantly higher levels of I-FABP and I-BABP than the controls. There were no differences in the serum D-lactate level between the cases and controls. There was no difference between the two groups of patients (I and II) regarding any of the parameters studied. No significant correlations between serum levels of I-FABP, I-BABP, or D-lactate and total or direct bilirubin levels were found in the cholestatic infants.Conclusions: The intestinal epithelial barrier integrity is breached nearly in all parts of the intestine in infants with cholestasis. Further research is recommended to determine the impact of this finding on the management of these infants. The relationship between physical intestinal barrier damage and its functional failure remains subject for further research

Evaluation of serum level of some angiogenic factors in non hodgkin's lymphoma

Background: Angiogenesis is a prerequisite for growth of tumors whether solid or liquid tumors. The process of angiogenesis is very complex and tightly regulated by positive and negative regulatory factors, the precise role of these processes in lymphoma pathogenesis is under active investigation. This work aimed at assessing serum levels of certain angiogenic factors in cases of non Hodgkin's lymphoma (NHL) whether newly diagnosed or relapsed and there correlations to disease progression and staging. Methods: Serum levels of certain positive regulatory factors for angiogenisis namely "Angiogenin, Nitric oxide, Copper", and Zinc as a negative regulatory factor were assayed, and Copper / zinc ratio were determined in 57 patients of NHL classified into four groups according to the disease stage investigated before the start of chemotherapy and 20 healthy controls. Result: Patients in 1 st group (stage I and II) showed significant elevation in serum levels of angiogenin, copper, and insignificant changes occurred in serum levels of zinc, nitric oxide and in copper zinc ratio in comparison with the control group. On the other hand; patients in 2 nd group (stage III) and 3 rd group (stage IV) showed highly significant increase in serum levels of copper and copper zinc ratio; while insignificant changes occurred in serum levels of angiogenin and nitric oxide. Conversely, highly significant decrease occurred in serum levels of zinc in 2 nd group only. Patients in 4 th group (relapsed cases) showed highly significant increase in serum levels of copper, significant increase in serum levels of angiogenin and in copper/inc ratio, while insignificant changes occurred in serum levels of zinc, and nitric oxide. The comparison between different patients groups revealed no significant differences in all special investigations except for zinc where there was a significant lower level of zinc in 2 nd group than 1 st group, and for copper and copper/zinc ratio; there were significant rise of each in 4thgroup in comparison to 1 st group. Conclusion: The serum angiogenin and copper levels may play an important role in early detection of NHL as it increased significantly in early stages, the highest levels were found in advanced cases together with low zinc level suggesting their role in follow up of NHL together with consideration of copper /zinc ratio while limited role of nitric oxid had been observed

Modified Adenovirus Reduces De Novo Peritoneal Adhesions in Rats and Limits Off-Target Transfection. Role of EZH2 in Adhesion Formation

Aim of the study: Adenovector encoding tissue plasminogen activator (tPA) was shown to reduce experimental peritoneal adhesion. We investigated the targeting potential of our modified adenovector, its ability to reduce adhesions and the epigenetic role of histone methyltransferase EZH2 in adhesion formation. Materials and methods: Control lacZ, nonmodified tPA or modified tPA vectors were instilled in the peritoneal cavity after injury in de novo adhesions or after lysis of adhesions in recurrent adhesions. Adhesion severity was scored and adhesions and liver tissues were examined for adenovirus E4 gene and tPA mRNA expression. Levels of tPA, plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-β1 (TGF-β1), and EZH2 expression were measured. Results: E4 transcripts were detected in adhesions of nonmodified and modified and in livers of nonmodified but not in livers of modified de novo adhesions. Both nonmodified (p = 0.021) and modified vectors (p = 0.036) reduced the severity of de novo adhesions compared to lacZ vector. Levels of tPA in nonmodified (p = 0.021) and modified adhesions (p = 0.001) were elevated while PAI-1 (p = 0.013 and p = 0.001, respectively) and TGF-β1 levels (p = 0.002 and p = 0.016, respectively) were reduced compared with lacZ group. All vectors were not expressed in recurrent adhesions and severity score were not different among groups. EZH2 levels were elevated in de novo nontreated (p = 0.001) and was further increased in recurrent (p = 0.001) nontreated adhesions compared with noninjured peritoneum. Conclusion: Modified adenovirus successfully targeted de novo adhesions but not liver tissues and reduced the severity of de novo adhesions. EZH2 is involved in the development and progression of peritoneal adhesions