Induction of 11beta-hydroxysteroid dehydrogenase type 2 and hyperaldosteronism are essential for enhanced sodium absorption after total colectomy in rats

BACKGROUND: Patients who undergo total colectomy with ileopouch anal reconstruction often have persistent diarrhea and frequent bowel movements. Analysis of the intestinal adaptation after total colectomy may lead to developing novel therapies for postoperative diarrhea. METHODS: Sprague-Dawley rats underwent total colectomy with ileoanal reconstruction and were sacrificed 4 and 8 weeks later. Mucosal response to aldosterone was evaluated with the use of ileal mucosa in an Ussing chamber by measuring short circuit current after in vitro stimulation with aldosterone. We investigated the expression of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD 2) in intestinal epithelial cells. To examine the role of hyperaldosteronism, we also evaluated rats treated with a sodium-deficient diet or subcutaneous aldosterone infusion. RESULTS: Aldosterone levels increased 80-fold after total colectomy. A comparable amount of aldosterone dramatically increased aldosterone-mediated, amiloride-sensitive short circuit current in the mucosa from colectomized rats, but not in control rats. We measured an increase in 11beta-HSD 2 messenger RNA and protein in the distal ileum from colectomized rats. Circulating aldosterone appears to be essential for these functional and molecular changes because similar results were obtained by using the mucosa from both dietary sodium-depleted and aldosterone-infused rats. CONCLUSIONS: Induction of 11beta-HSD 2 is essential for enhanced mineralocorticoid action in the remnant ileum after total colectomy in rats.     

Expression of hepatitis B surface antigen subtypes in liver of patients with hepatocellular carcinoma; comparison of subtypes in serum and liver

ABSTRACT— To clarify the discrepancy in hepatitis B surface antigen (HBsAg) subtypes present in the serum and liver, as well as among hepatocytes, liver specimens which were resected from 37 HBsAg-positive patients with hepatocellular carcinoma (HCC) were examined. We evaluated HBsAg and the subtypic determinants of HBsAg and hepatitis B core antigen (HBcAg) using the peroxidase-antiperoxidase (PAP) staining method. Hepatitis B antigens were more frequently detected in small tumors (HBsAg in 67%, HBcAg in 40%) than in large ones (HBsAg in 36%, HBcAg in 14%). The prevalence of each subtypic determinant in the HBsAg positive non-tumorous vs. tumorous areas was 100% vs. 67% in a, 100% vs. 57% in d, 100% vs. not tested in y, 100% vs. 53% in r and 25% vs. 0% in w (a, d, y, r and w represent subtypic determinants). There was virtually no difference in a set of subtypic determinants between the serum and liver. However, there were some variations in a set of subtypic determinants among the hepatocytes. On the other hand, liver tissue of compound subtype adyr in serum contained both cells with a,d,r and with a,y,r as well as a few cells with a,d,y,r. These findings suggest that HBV genomes in hepatocytes of type B chronic liver disease may differ genetically among cells even in the same liver tissue.     

Vasospastic angina in Kawasaki disease

We report vasospastic angina in a young female with a history of Kawasaki disease (KD). She had had KD at the age of 20 months. Selective coronary angiograms at the age of 4 years revealed no coronary aneurysms or stenosis. She remained symptom-free for 29 years, but coronary angiograms at the age of 31 years revealed a localized 50% stenosis of the left anterior descending artery. Aging in addition to endothelial dysfunction of the coronary arterial wall resulting from acute KD vasculitis may underlie the late development of angina. This is the first case which is reported as vasospastic angina after KD. The occurrence of acute coronary syndromes in patients with a history of KD should be investigated carefully from now on. Attention should be paid to coronary endothelial dysfunction after KD in adults.     

Triiodothyronine generation from thyroxine in human thyroid: enhanced conversion in Graves' thyroid tissue

Conversion of T4 to T3 was studied in normal, Graves', and neoplastic thyroid tissues obtained at surgery. Homogenates of human thyroid follicular adenoma and carcinomas were incubated with [125I]T4 and dithiothreitol (DTT) at 37 C for 60 min under N2 gas. T3 formation was assessed by measuring [125I]T3 formed, using paper chromatography. In the second series of experiments, the suspensions of the 100,000 X g pellet of normal thyroid tissues adjacent to the tumor and Graves' thyroid tissues were incubated with unlabeled T4 and DTT at 37 C for 60 min under N2 gas. T3 generated was measured by RIA. T3 generation in the thyroid tissue was dependent on incubation time, amount of the tissue used, concentration of DTT, temperature, and pH. Propylthioracil inhibited T3 formation, while methimazole had no effect. A kinetic study with the homogenate of a thyroid adenoma and 100,000 X g pellet suspensions of two normal and three Graves' thyroids gave apparent Km values of 2.7, 4.9, and 4.1 microM for T4, respectively, and Vmax values of 0.8, 3.0, and 10.9 pmol T3/mg protein.min, respectively. Conversion of T4 to T3 was observed in two of three tumor tissues studied and was markedly enhanced in Graves' thyroid tissues (mean +/- SE, 11.9 +/- 2.0 pmol/mg protein.min) compared to that of normal thyroid tissues (3.2 +/- 0.6 pmol/mg protein.min; P less than 0.01). It is concluded that T4 is enzymatically converted to T3 in normal and Graves' thyroids and differentiated thyroid neoplasms. Moreover, enhanced conversion of T4 to T3 was found in Graves' thyroid tissue.     

Plasma level of homocysteine is correlated to extracranial carotid-artery atherosclerosis in non-hypertensive Japanese

BACKGROUND: Results of some epidemiologic studies in Western countries have clarified that hyperhomocysteinemia is a plausible risk factor for atherosclerotic vascular disease, but its role in Japanese communities is not known. DESIGN: A community-based cross-sectional design. METHODS: We performed a cross-sectional study of 474 elderly men aged 60-74 years in two Japanese rural communities (Noichi in southwestern Japan and Ikawa in northeastern Japan). We examined the association between plasma concentrations of homocysteine and the maximum intima-media thickness (assessed by ultrasonography). RESULTS: The prevalence of thickening was 10.7% for the lowest tertile of homocysteine level and 21.1% for the highest tertile. For the subjects without hypertension, the odds ratio for having carotid intima-media thickening was 5.8; it was significantly higher for the highest tertile of homocysteine level than it was for the lowest after adjusting for age, hypercholesterolemia, hypoalphalipoproteinemia, diabetes, and smoking by using a multiple logistic regression model. However, its correlation was not evident for those with hypertension. CONCLUSIONS: High levels of plasma homocysteine are correlated to extracranial carotid artery atherosclerosis in elderly men without hypertension in Japanese rural communities.