Colonic mucosal vasoactive intestinal peptide receptors in malformations of the enteric nervous system are reduced compared with morphologically normal innervated colon.

Vasoactive intestinal peptide (VIP) is the most important peptidergic transmitter in intestinal relaxation. VIPergic nerves are reduced in aganglionosis (AG). Corresponding findings in intestinal neuronal dysplasia (IND) are sparse. It is unknown whether superficial mucosal VIP receptors are reduced in AG, IND, or hypoganglionosis (HYP) compared to concentrations in morphologically normal innervated colon (MNIC). Cryostat sections from 38 colonic biopsies (23 patients with AG, IND. or HYP, 15 with MNIC) were incubated with radioactive iodinated 125 I-VIP. Receptors were analyzed by autoradiography. Radioactive-marked receptors trigger the precipitation of metallic silver as silver grains within a photographic emulsion. Grains were quantified by image analysis, calculating the percent covered cell surface. Statistical analysis was done by Mann-Whitney and Kruskal-Wallis tests (significance P < 0.05). VIP receptors covered 4.31% of the cell surface in MNIC. The values were significantly reduced in AG (2.72%; P=0.012) and IND (2.93%; P = 0.008). The two HYP biopsies showed the lowest values (1.83%). Aganglionic colon could be distinguished from healthy proximal segments and IND from habitual constipation. In AG and IND, even the superficial mucosal VIPergic innervation seems to be impaired. The reduction of mucosal VIP receptors in developmental faults of the enteric nervous system may thus be an indicator of a sensomotor disturbance

Identification and in Situ Localization of the Insulin-like Growth Factor-II/mannose-6-phosphate ( IGF-II/M6P) Receptor in the Rat Gastrointestinal Tract: Comparison with the IGF-I Receptor.

In the present study we investigated pharmacological, biochemical, and immunological characteristics as well as the tissue distribution of the insulin-like growth factor-II/man nose-6-phosphate (IGF-II/M6P) receptor in the rat gastrointestinal tract, and compared the data with those from corresponding experiments for the IGF-I receptor. Competitive binding and affinity cross-linking studies with [125I]IGF-II, and [125I]IGF-I respectively, in rat jejunum yielded results analogous to those previously obtained for IGF-II/M6P and IGF-I receptors in intestinal epithelial membranes and other tissues. Furthermore, the IGF-II/M6P receptor antibody no. 3637 completely inhibited the association of [125I]IGF-II with receptor protein but nonimmune antibody did not, providing additional evidence for the presence of the IGF-II/M6P receptor in the rat gut. Also, analysis of the IGF-II/M6P receptor by immunoblotting using antiserum no. 3637 identified a specific band of mol wt 220.000 throughout the gastrointestinal tract with the highest content of immunoreactivity being present in colon and ileum

Copper induced hepatotoxicosis with hepatic stellate cell activation and severe fibrosis in North Ronaldsay lambs: a model for non-Wilsonian hepatic copper toxicosis of infants

Copper-sensitive North Ronaldsay sheep represent a possible model for certain hepatic-overload syndromes of infancy and childhood that are clinically, pathologically and genetically distinct from Wilson's disease. The purpose of this study was to simulate in artificially reared lambs the syndrome produced by copper exposure in susceptible human infants. Twenty four North Ronaldsay lambs were assigned to three groups of eight animals, namely, an unsupplemented control group and two trial groups given milk replacer to which copper (CuSO4) had been added at the rate of 5 mg/litre and 10 mg/litre. Four lambs from each group were killed at 40 or 69 days. Livers were fixed in 10% formalin and analysed for copper by mass spectrometry. Paraffin wax-embedded sections were stained with rhodanine for copper and labelled immunohistochemically for α smooth muscle actin (ASMA). At 40 days the maximum amounts of copper in the livers of both copper-supplemented groups was 1466–1605 μg/g dry weight (control group 172–201 μg/g Cu dry weight). Histochemically, copper was demonstrated within hepatocytes, together with marked apoptosis. At 69 days there was a florid pericellular fibrosis complemented by strong ASMA immunolabelling, confirming phenotypic modulation of hepatic stellate cells. Such primary copper-induced fibrogenesis confirms the unique status of this animal model in respect of childhood copper toxicosis