Iron absorption in Crohn\u27s Disease

Anemia is observed in a considerable number of patients with Chohn\u27s disease (CD). Iron absorption was investigated, using radioactive iron (^FeCl_3), in 12 normal subjects (controls), seven patients with iron deficiency anemia (ID), and 23 patients with CD. After oral administration of 1 μ Ci of ^Fe with 4 mg of FeSO_4 as a carrier, serum ^59Fe levels were determined for approximately three hours with a liquid scintillation counter. The proportion of iron remaining in the body two weeks after administration was also determined as the absorption ratio by whole-body counting. In investigating the factors affecting the absorption ratio, erythrocyte count, hemoglobin, total protein, albumin, serum iron (Fe), serum transferrin (TS), and serum ferritin were used as dependent variables, and were subjected to a multiple regression analysis for the prediction of the absorption ratio. The analysis revealed that hemoglobin and ferritin levels correlated significantly with the absorption ratio. The absorption ratio was not useful in differentiating between ID and CD patient, while both TS and ferritin were useful in differentiating between CD, ID and normal subjects. The time-course change in serum ^Fe after administration of ^Fe showed slightly higher levels in ID and CD than in controls

Flow Cytometric Nuclear DNA Analysis in Ulcerative Colitis

The purpose of this study was to assess the usefulness of nuclear DNA analysis in early cancer detection in patients with ulcerative colitis. The results of flow cytometric nuclear DNA anaiysis of tissue specimens from patients with ulcerative colitis, colonic adenoma, and colorectal carcinoma were compared. DNA aneuploidy was observed in 53.1 % of patients with ulcerative colitis and 16.7 % of patients with colonic adenoma. The degree of atypism of the tumor cells was related to the incidence of DNA aneuploidy. DNA aneuploidy was noted in 48.6 % of the patient with ulcerative colitis and coexistent colorectal carcinoma. The degree of dysplasia of the tumor cells was also correlated with the incidence of DNA aneuploidy. DNA aneuploidy was found in 14.3 % of specimens of mucosal tissue that were without cancerous or dysplastic cells. DNA aneuploidy was found in 8.5 % of specimens of mucosal tissue collected from patients with ulcerative colitis alone. Our findings showed that abnormalities in DNA content was closely correlated with histological atypism. In addition, our findings suggested that DNA aneuploidy may precede dysplastic changes in some cases of ulcerative colitis. We concluded that DNA analysis using flow cytometry is a useful method for identification of patients with ulcerative colitis at high risk for the development of cancer

Eosinophil Cationic Protein (ECP) in Ulcerative Colitis

One of the eosinophil granule proteins is eosinophil cationic protein (ECP) which is basic and cytotoxic. The association of ECP in ulcerative colitis (UC) was studied by immunohistochemical method and RIA. ECP was localized in the lamina propria and the interstitium of the UC colon mucosa, showing a significant increase in distribution compared to the control. The ECP content, which was compared among the three groups according to the severity of UC classified by Matts\u27 histopathological classification, disclosed an increasing tendency as the histological severity increased. The serum ECP level in active UC 17.68±12.25μg/L (n = 21) was significantly higher than that in inactive UC. In view of these findings, it was speculated that ECP has a role, though partial, in the damage of the colonic mucosa in UC on the basis of its biological features

The effect of the gastrointestinal hormones on colonic mucosal blood flow

The effect of intravenous administration of various gastrointestinal hormones or peptides on the colonic mucosal blood flow was investigated by a reflex spectrum apparatus (TS-200, Sumitomo Denko Co). Various gastrointestinal hormones (pentagastrin, secretin, substance P, vasoactive intestinal polypeptide) were administered via the femoral vein at different doses. The hormones were administered over 30 minutes using a chronofuser at a rate of 0.1 ml/min. Serial measurements of cecal mucosal blood flow were performed. Saline was administered to the control group. 1) Pentagastrin was administered at doses of 1μg/kg/hr, 50μg/kg/hr, 100μg/kg/hr, and 200μg/kg/hr. Cecal mucosal blood flow decreased when the dose of pentagastrin was increased. The intravascular supply of oxygen also decreased in a dose dependent manner. Each dose of the gastrointestinal hormone caused a reduction in blood pressure. 2) Secretin was administered at doses of 5μg/kg/hr, 50μg/ kg/hr, and 100μg/kg/hr. Each tested dose of this gastrointestinal hormone acted to maintain cecal mucosal blood flow. The blood pressure remained unchanged throughout the experiment. 3) Substance P was administered at doses of 1μg/kg/hr and 5μg/kg/hr. Cecal mucosal blood flow and the intravascular oxygen supply increased after administration of this gastrointestinal hormone. The blood pressure decreased transiently at the start of administration, but later gradually returned to the baseline values. 4) Vasoactive intestinal polypeptide (VIP) was administered at doses of 1μg/kg/hr, 5μg/kg/hr, and 10μg/kg/hr. VIP caused the cecal mucosal blood flow to increase in a dosedependent manner. The intravascular oxygen, supply also increased signific antly after administration of this gastrointestinal hormone. The blood pressure initially de creased after administration of each test dose of VIP, after which it gradually started to increase. 5) To identify the factors responsible for the increase in cecal mucosal blood flow at the start of VIP administration at a dose of 5μg/kg/h of VIP, the blood concentrations of VIP, cyclic AMP, phospholipase, prostaglandin E_2, prostaglandin: E, and 6 keto-prostaglandin:F_1α were examined at regular intervals. However, no significant changes with regard to these substances were noted

Inhibitory effect of spleen X-ray irradiation on dextran sulfate sodium-induced colitis in the mouse

Dextran sulfate sodium (DSS) solution was orally administered to mice to experimentally induce colitis, and the effects of X-ray irradiation of the spleen on healing or prolongation of inflammation was investigated. Peripheral, splenic and thymic T lymphocyte subsets were also analyzed to assess the underlying morbid conditions. Colitis with inflammatory changes consisting mainly of hemorrhagic erosions at the distal large intestine was induced by the administration of a 2 % DSS solution for 14 consecutive days. The DSS-induced colitis was inhibited by pre-irradiation of the spleen with 20 Gy prior to the development of DSSinduced colitis. Healing of inflammed lesion was accelerated by irradiation with 20 Gy during the induction of colitis with DSS. The proportion of peripheral Thy-1^+ and L3T4^+ cells was higher while the proportion of splenic L3T4^+ cells was significantly lower compared with the control group during the preparation of DSS-induced colitis. At 2 and 7 days after pre-irradiation, peripheral and splenic Thy-1^+ and L3T4^+ cells increased and thymic Lyt-2^- . L3T4^+ cells increased, whereas thymic Lyt-2^+ . L3T4^+ cell decreased. Our results suggest that the effect of splenic irradiation on DSS-induced colitis is due to a stimulation of T cell function, and activation of the immune system

Regulation of Colonic Mucosal Blood Flow by Exogenous Ecosanoids in the Rat

We measured colonic mucosal blood flow using a reflectance spectrophotometry in Wistar rats during and after continuous injection of prostaglandins (PGs: PGE1, PGE2 and PGI2), as vasodilators, and thromboxane A2 (TXA2) as a vasoconstrictor. Administration of PGs increased colonic mucosal blood volume and oxyhemoglobin saturation of the colonic mucosal tissue, representing a parameter of mucosal oxygenation. The dose used did not change arterial blood pressure. These results suggest that PGs regulate colonic mucosal hemodynamics and oxygenation, and may thus act as cytoprotective substances. On the other hand, TXA2 injection diminished colonic mucosal blood flow compared with the same dose of PGI2 injection and acted against PGI2. Our results suggest that TXA2 and PGI2 regulate colonic mucosal hemodynamics

Phenotype and cytokine production of Lamina Propria Mononuclear Cells from Endoscopic Biopsy Specimens in Untreated Patients with Ulcerative Colitis

The phenotype of, and the production of interleukinl-β(Ｉ L-1β)and interleukin 6(IL、-6)by lamina propria mononuclear cells (LPMNC) were studied in 25 patients with ulcerative colitis (UC) (11 with untreated active disease and 14 inactive disease), and 18 control subjects. The percentage of CD4+ cells, CD20+ cells, CD3+, CD25+ cells and CD3+, HLA-DR+ cells was significantly higher in patients with active UC than in control patients, however, the percentage of CD8+ cells was significantly lower in patients with active UC than in patients with inactive UC and controls. IL-1 β was detected in nine of the ll patients(82%) with active UC but in only two of the 14 patients (14 %) with inactive UC and three of the 18 control subjects (17 %). The amount of IL-6 in patients with active UC was significantly higher than in patients with inactive UC and in controls. These results suggest that IL-1β and IL-6 mediate immune responses, and may be associated with inflammation and the etiopathogenesis of UC

Experimental-Induced Colitis in Rats by Ethanolic Solution of Trinitrobenzene Sulfonic Acid and Ethanol Alone : A Comparative Study

Epidemiological data suggest an increase in both developed and undeveloped countries of inflammatory bowel disease. Furthermore, its etiology and pathophysiology remain unknown. Appropriated animal models are needed. We have studied a rat model of hapten-induced chronic colitis. In Wistar rats, intracolonic instillation of 20 mg or 42 mg of the hapten trinitrobenzene sulfonic acid in 30 % and 40 % ethanol proved to induce chronic colitis after 14 to 21 days of administration, in dose-dependent fashion when compared with ethanol alone that induced only acute colitis after three days of administration. This chronic colitis shares some characteristics with inflammatory bowel disease in humans, specially with Crohn\u27s disease, such as transmural inflammation, development of strictures, ulcerations and infiltration of inflammatory cells throughout the colonic wall. These features make this model suitable for further studies of intestinal inflammation

Distribution and Localization of Endocrine Cells in the Human Gastro-intestinal Tract -In Relation to Histogenesis of Rectal Carcinoid-

The distribution of endocrine cells in the human intestine was studied by immunostaining using the labeled avidinbiotin technique. The total number of endocrine cells was abundant in the proximal portion of the small intestine and the distal portion of the large intestine. Gastrin, cholecystokinin, and motilin immunoreactive cells were localized in the proximal portion of the small intestine. Peptide YY, serotonin, and glucagon/glicentin immunoreactive cells were distributed more abundantly in the lower large intestine. The serotonin and somatostatin concentrations in the colonic mucosa determined by high-performance liquid chromatography and radioimmunoassay were higher in the distal than proximal portion of the large intestine, being in correlation with the distribution of serotonin and somatostatin immunoreactive cells estimated by immunostaining. Therefore, the regional differences in the number of endocrine cells and the mucosal concentrations of the hormones probably reflect differences in the physiological functions of different regions of the gut. Not many endocrine cells with unknown peptides and animes and immature endocrine cells were present in the lower large intestine. Therefore, the frequent occurrence of carcinoids in the rectum is difficult to explain by the quantitative dominance of endocrine cells alone in the rectal mucosa, and other factors are considered to need evaluation

Effects of Dexamethasone on Interleukin-6 and Immunoglobulins Production by Lamina Propria Mononuclear Cells Isolated from Biopsy Specimens in Patients with Ulcerative Colitis

Lamina propria mononuclear cells (LPMNC) were isolated from 20 untreated patients with active ulcerative colitis (UC) and 11 patients with inactive UC. All patients with active UC were first attacks, and were not being treated with any drugs. The effects of dexamethasone on production of interleukin-6 (IL-6) and immunoglobulins by LPMNC were assessed. IL-6 production by LPMNC, stimulated by pokeweed mitogen (PWM), was higher in patients with active UC (663.3±213.1 pg/ml) compared with normal controls (129.0 ±39.0 pg/ml) and patients with inactive UC (219.6 ± 63.4 pg/ ml). IgG was produced in greater amount by the LPMNC from patients with active UC (1395.5 ± 876.6 ng/ml) than by those from controls (413.0 ± 471.2 ng/ml) and patients with inactive UC (488.3±552.0 ng/ml) (p < 0.001). The amount of IgA and IgM did not vary among three groups. Dexamethasone suppressed the production of IL-6 and IgA, IgG and IgM by PWM-stimulated LPMNC in a dose-dependent manner in the dose range between 10-5and 10-2 mg/dl. We speculate that the suppression of IL-6 production by dexamethasone will contribute to the suppression of UCassociated inflammatio