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Alessio Fasano

Publications and source records attributed to Alessio Fasano.

42 records · Page 3Linked to original sources

New developments in childhood celiac disease.

Celiac disease (CD) is one of the most common lifelong disorders in Europe and the United States, in both children and adults. It is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. This review addresses new developments in CD with respect to pediatric patients and emphasizes the need for awareness among health-care professionals. The epidemiology, pathophysiology, diagnosis, and clinical spectrum of CD in children are highlighted.

Algorithms↗

Ganglioside reactive antibodies in the neuropathy associated with celiac disease.

We tested patients with celiac disease (CD) for the presence of serum anti-ganglioside antibodies. Six of twenty-seven patient sera were reactive against brain gangliosides by an agglutination immunoassay. Neurological examination in all six revealed the presence of distal sensory loss, consistent with the diagnosis of peripheral neuropathy. When tested by ELISA for antibodies to isolated GM1, GM2, GD1a, GD1b, GT1b, and GQ1b gangliosides, all six were positive for IgG antibodies to at least one. The neuropathy of celiac disease may be autoimmune and associated with anti-ganglioside antibodies. The presence of IgG reactivity furthermore implicates a T cell-mediated response to ganglioside antigens.

Adult↗

Structural and functional alterations of the gastrointestinal tract following radiation-induced injury in the rhesus monkey.

A severe and debilitating diarrhea is a dose-limiting toxic result for patients receiving abdominal radiation or chemotherapy. To correlate changes in intestinal structure and function, nonhuman primates were exposed to 9.5 Gy total abdominal x-irradiation. Diarrhea and weight loss were correlated with intestinal crypt and villus histology, in vivo assessed intestinal permeability, and ex vivo functional studies performed in Ussing chamber assays before and at 7, 14, and 35 days after irradiation. Peak gut structural damage occurred early and paralleled functional changes of the intestinal mucosa, including increased epithelial permeability (both in vivo and ex vivo), activation of secretory pathways, decreased nutrient absorption, diarrhea, and weight loss. Recovery of gut integrity and epithelial resistance began thereafter, in spite of incomplete histological recovery. Our integrated approach allowed a comprehensive study of the relationship between postirradiation tissue injury and changes in function over time in the gastrointestinal tract of the nonhuman primate.

Animals↗

Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure.

BACKGROUND & AIMS: Enteric infections have been implicated in the pathogenesis of both food intolerance and autoimmune diseases secondary to the impairment of the intestinal barrier. On the basis of our recent discovery of zonulin, a modulator of small-intestinal tight junctions, we asked whether microorganisms might induce zonulin secretion and increased small-intestinal permeability. METHODS: Both ex vivo mammalian small intestines and intestinal cell monolayers were exposed to either pathogenic or nonpathogenic enterobacteria. Zonulin production and changes in paracellular permeability were monitored in Ussing chambers and micro-snapwells. Zonula occludens 1 protein redistribution after bacteria colonization was evaluated on cell monolayers. RESULTS: Small intestines exposed to enteric bacteria secreted zonulin. This secretion was independent of either the species of the small intestines or the virulence of the microorganisms tested, occurred only on the luminal aspect of the bacteria-exposed small-intestinal mucosa, and was followed by a decrease in small-intestinal tissue resistance (transepithelial electrical resistance). The transepithelial electrical resistance decrement was secondary to the zonulin-induced tight junction disassembly, as also shown by the disengagement of the protein zonula occludens 1 protein from the tight junctional complex. CONCLUSIONS: This zonulin-driven opening of the paracellular pathway may represent a defensive mechanism, which flushes out microorganisms and contributes to the host response against bacterial colonization of the small intestine.

Animals↗

Zonula occludin toxin, a microtubule binding protein.

AIM:To investigate the interaction of Zot with microtubule.METHODS:Zot affinity column was applied to purify Zot-binding protein(s) from crude intestinal cell lysates. After incubation at room temperature, the column was washed and the proteins bound to the Zot affinity column were eluted by step gradient with NaCl (0.3molcenter dotL(-1) -0.5molcenter dotL(-1)). The fractions were subjected to 6.0%-15.0% (w/v) gradient SDS-PAGE and then transferred to PVDF membrane for N-terminal sequencing.Purified Zot and tau protein were blotted by using anti-Zot or anti tau antibodies. Finally, purified Zot was tested in an in vitro tubulin binding assay.RESULTS:Fractions from Zot affinity column yielded two protein bands with a M(r) of 60kU and 45kU respectively. The Nterminal sequence of the 60kU band resulted identical to beta-tubulin. Zot also crossreacts with antitau antibodies. In the in vitro tubulin binding assay, Zot coprecipitate with Mt, further suggesting that Zot possesses tubulin-binding properties.CONCLUSION:Taken together, these results suggest that Zot regulates the permeability of intestinal tight junctions by binding to intracellular Mt, with the subsequent activation of the intracellular signaling leading to the permeabilization of intercellular tight junctions.

Journal Article↗