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.

Preoperative interleukin-6 in colorectal cancer patients: correlation with carcinoembryonic antigen, tumour stage and outcome

The significance of preoperative serum inter-leukin-6 [IL-6] level in the progression of colorectal cancer has not been fully elucidated. Our aim was to investigate its role and identify its prognostic significance. Forty three consecutive patients, who underwent radical resections for colorectal cancer lesions in a period of 1.5 years from Aug. 2004 till Feb. 2006 were recruited in this study. Blood samples were obtained before surgery to determine the serum concentration of IL-6 and carcinoembryonic antigen [CEA]. Serum concentrations of human IL-6 were determined by enzyme-linked immunosor-bent assay [ELIZA] and CEA was measured by immunometric method. The relationships between their elevations and both the clincopathological factors and prognosis of patients were investigated. Serum samples [for IL-6 assay only] from 25 sex- and age-matched normal healthy individuals were used as controls. The mean serum IL-6 concentration [9.57 +/- 7 pg/mL, range 2.4-45 pg/mL] was significantly higher than that in normal individuals [mean value: 3.52 pg/mL, range 0.45-9.96 pg/mL, p<.001]. Elevated serum CEA [>5.0 ng/mL] was present in 44.2% of patients, while serum IL-6 levels in CRC patients were more frequently elevated [69.8% of patients, p=.001]. Linear regression analysis showed a significant association between serum values of both IL-6 and CEA [r=.773; r[2]=.597; p=.001]. The mean IL-6 serum concentration in CRC patients with stage III was 13.3 +/- 8.47 pg/mL while the mean level in patients with stage I and II was 6.3 +/- 3 pg/mL [p=.001]. Patients with an IL-6 serum concentration of more than 9.5 pg/ml had a significantly shorter 2-year survival [55%] than patients with an IL-6 serum concentration of 9.5 pg/ml or less [93%], [p=001]. IL-6 is potentially a better marker for advanced colorectal carcinoma than CEA. High preoperative levels were associated with high CEA, advanced tumor stage and poor outcome. IL-6 may have a role as an indicator of metastases that appear after resection of the primary colon cancer. This may help to identify high risk patients more likely to benefit from adjuvant therapy

Pulmonary hypertension in thalassemic children: does endothelial dysfunction play a role?

The thalassemia syndromes are a heterogeneous group of inherited hemoglobin disorders resulting from impaired production of either the alpha or beta globin chain subunits of the hemoglobin tetramer. Heart failure is the most common cause of death in thalassemia. Thalassemic heart disease involves mainly left ventricular dysfunction caused by transfusion- induced iron overload. However, recent studies suggest that TM patients have a unique hemodynamic pattern consistent with right ventricular cardiomyopathy, and pulmonary hypertension in addition to the LV abnormalities. Pulmonary hypertension in beta-thalassemia could represent a common, yet less well-explored complication in the cardiopulmonary spectrum of the disease. The aim of this study is to determine serum levels of cholesterol, triglycerides, nitric oxide [NO], endothelin-1 [ET-1], lnterlukin-6 [lL-6] and the soluble forms of vascular cell adhesion molecule [sVCAM-1] as well as intercellular adhesion molecule [sICAM-1] in transfusion-dependent beta-thalassemia children and to correlate these markers with the echocardiographic findings as well as serum ferritin of these patients. The study included 32 transfusion-dependant children with beta-thalassemia aged 5 to 15 years and 40 apparently healthy children as a control group. Serum levels of cholesterol, triglycerides, NO, ET-1, lL-6 and the soluble forms of vascular cell adhesion molecule [sVCAM-1] as well as intracellular adhesion molecule [sICAM-1] were determined for patients and controls. In addition echocardiography was also done. Serum levels of ET-1, lL-6 and the soluble forms of vascular cell adhesion molecule [sVCAM-1] as well as intracellular adhesion molecule [sICAM-1] were significantly higher in the studied cases than the controls while serum levels of cholesterol and NO were significantly lower. Echocardiographic evidence of pulmonary hypertension was detected in 68.75% of the cases. The lassemic cases with PHT had significantly higher values of ET-1, lL-6, VEGF, sICAM and sVCAM than those without PHT. Pulmonary hypertension in beta-thalassemia could be an additional complication in the cardiopulmonary spectrum of the disease due to NO deficiency as a result of iron overload and endothelial dysfunction. Therapeutic interventions that decrease hemolytic rate, improve, enhance NO effects, or act as NO donors are of potential benefit and may alter the progression of the disorder