Epithelial proliferation and ras p21 oncoprotein expression in rectal mucosa of patients with ulcerative colitis.

In ulcerative colitis (UC), epithelial proliferation plays a role in crypt repair and neoplastic evolution. Proliferative status is predominantly connoted in active disease, but not defined in remission. Histologically, remission is characterized by normalization of the picture or development of atrophy. Mutation of the ras oncogene is involved in intestinal carcinogenesis. Aim of this work was to assess the proliferative pattern of rectal epithelium in UC during disease activity and in remission and correlate it with ras oncoprotein p21. The study was performed retrospectively in rectal biopsies from four groups each of 10 patients: active ulcerative colitis (AUC), remission with a normal histology (RUC), remission with rectal atrophy (ARUC), and irritable bowel syndrome (C, control group). In all, immunohistostain was employed to evaluate the proliferation cell nuclear antigen labeling index (PCNA LI) and ras p21. Statistical analysis was performed by ANOVA and Student-Neumann-Keuls tests. PCNA LI was significantly higher in AUC and ARUC than in RUC and C. Positive cells were predominant in the lower zone of crypts in RUC and C, while a significant expression of PCNA was also observed in the upper areas in AUC and ARUC. Oncoprotein p21 was expressed on the apical surface of the epithelium in 3/10 AUC patients, in all 10 ARUC patients and in none of RUC and C. The persistently increased epithelial proliferation associated with ras p21 expression in ARUC may be due to the action of an abnormal, mutated ras gene that could play a role in UC-related tumorigenesis.

Immunohistochemical detection of Helicobacter pylori vacuolating cytotoxin in the hepatocytes of patients with isolated hypertransaminasaemia.

BACKGROUND AND AIM: Even if different Helicobacter species can colonise animal livers and induce hepatitis, there is no evidence that Helicobacter pylori can damage this organ and only a potential capacity of cytotoxic strains to increase transaminases in humans has been suggested. We have, therefore, carried out an immunohistochemical study on vacuolating cytotoxin in the hepatocytes of subjects with isolated hypertransaminasaemia. PATIENTS, METHODS AND RESULTS: Five male patients with isolated hypertransaminasaemia without signs of known causes of liver diseases were studied. Endoscopy demonstrated diffuse mucosal hyperaemia in 3 patients and duodenal ulcer in one. Histology revealed active chronic pangastritis in all. Helicobacter pylori was assessed by histology and culture and its cytotoxity, demonstrated by positive immunoblotting for both anti-CagA and VacA. Percutaneous liver biopsy showed minimal changes. Hepatic and gastric sections were tested either with autologous serum and rabbit antibody to VacA toxin. Immune reaction was revealed by immunoperoxidase. Both autologous sera and anti-VacA toxin antibody showed a reaction with a similar pattern which involved 60% of hepatocytes. Anti-VacA toxin showed a reaction to gastric epithelial cells and autologous sera to parietal cells in 4/5 patients. All patients received triple therapy and eradication of Helicobacter pylori was assessed by urea breath test. Serum transaminase levels 3 months after eradication, are still abnormal. CONCLUSIONS: Our immunohistochemical findings suggest that vacuolating cytotoxin could reach the hepatocytes of patients suffering from both isolated hypertransaminasaemia and infection by cytotoxic strains of Helicobacter pylori. Nevertheless, a clear relationship between these two condition remains uncertain.

Evaluation of a rapid protocol for the assessment of salt sensitivity against the blood pressure response to dietary sodium chloride restriction.

The "gold standard" for the assessment of salt sensitivity of hypertension is the blood pressure response to dietary NaCl restriction; nevertheless, for practical purposes, a more rapid test that would not depend on the patient's compliance to the dietary prescription would be very useful in clinical research and medical practice. The aim of this study was thus to evaluate the effectiveness and reliability of a rapid, easy-to-standardize protocol for the assessment of salt sensitivity against the blood pressure response to dietary salt restriction. A total of 108 hypertensive patients were screened for salt sensitivity by the modified protocol of Grim et al. Thereafter, nine patients identified by the test as salt sensitive and nine identified as salt resistant followed, for two consecutive periods of 1 week, a diet with normal (200 mmol/day) or low (50 mmol/day) NaCl content. Compliance to the diet was checked by repeated 24-h urine collections. The group as a whole experienced a significant fall in blood pressure during the low Na diet (mean pressure = 123 +/- 3 v 118 +/- 3 mm Hg; P < .05). However, whereas patients identified as salt sensitive by the Grim protocol had a marked and significant blood pressure decrease (systolic -12 mm Hg, diastolic -7 mm Hg), no change was observed in those classified as salt resistant (systolic -2 mm Hg, diastolic -2 mm Hg). A significant correlation between changes in urinary Na excretion and changes in blood pressure was found only in salt-sensitive hypertensive patients. In conclusion, the modified Grim protocol tested in this study was able to correctly predict a significant blood pressure response to dietary salt restriction in the majority of cases. A validation of this test in a larger patient population may be advisable.