Background: Recent studies suggest that coeliac disease (CD) is one of the commonest, life‐long disorders in Italy. The aims of this multicentre work were: (a) to establish the prevalence of CD on a nationwide basis; and (b) to characterize the CD clinical spectrum in Italy. Patients and methods: Fifteen centres screened 17201 students aged 6–15 years (68.6% of the eligible population) by the combined determination of serum IgG‐ and IgA‐antigliadin antibody (AGA) test; 1289 (7.5%) were IgG and/or IgA‐AGA positive and were recalled for the second‐level investigation; 111 of them met the criteria for the intestinal biopsy: IgA‐AGA positivity and/or AEA positivity or IgG‐AGA positivity plus serum IgA deficiency. Results: Intestinal biopsy was performed on 98 of the 111 subjects. CD was diagnosed in 82 subjects (75 biopsy proven, 7 not biopsied but with associated AGA and AEA positivity). Most of the screening‐detected coeliac patients showed low‐grade intensity illness often associated with decreased psychophysical well‐being. There were two AEA negative cases with associated CD and IgA deficiency. The prevalence of undiagnosed CD was 4.77 × 1000 (95% CI 3.79–5.91), 1 in 210 subjects. The overall prevalence of CD, including known CD cases, was 5.44 × 1000 (95% CI 4.57–6.44), 1 in 184 subjects. The ratio of known to undiagnosed CD cases was 1 in 7. Conclusions: These findings confirm that, in Italy, CD is one of the most common chronic disorders showing a wide and heterogeneous clinical spectrum. Most CD cases remain undiagnosed unless actively searched.

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In children with IBD, inflammation is an important determinant of bone loss, as shown by the correlation of BMAD with serum IL-6 and with disease activity indexes as well as by the beneficial effect of IFX on bone density. Corticosteroids seem to be a less important variable in pediatric IBD-related BMD reduction than previously believed.

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Oxidosqualene cyclase of the yeast encoded by the ERG7 gene converts oxidosqualene to lanosterol, the first cyclic component of sterol biosynthesis. In a previous study (Athenstaedt, K., Zweytick, D., Jandrositz, A, Kohlwein, S. D., and Daum, G. (1999) J. Bacteriol. 181, 6441-6448), Erg7p was identified as a component of yeast lipid particles. Here, we present evidence that Erg7p is almost exclusively associated with this compartment as shown by analysis of enzymatic activity, Western blot analysis, and in vivo localization of Erg7p-GFP. Occurrence of oxidosqualene cyclase in other organelles including the endoplasmic reticulum is negligible. In an erg7 deletion strain or in wild-type cells treated with an inhibitor of oxidosqualene cyclase, the substrate of Erg7p, oxidosqualene, accumulated mostly in lipid particles. Storage in lipid particles of this intermediate produced in excess may provide a possibility to exclude this membrane-perturbing component from other organelles. Thus, our data provide evidence that lipid particles are not only a depot for neutral lipids, but also participate in coordinate sterol metabolism and trafficking and serve as a storage site for compounds that may negatively affect membrane integrity. Oxidosqualene cyclases (OSCs)1 play a central role in sterol biosynthesis because they catalyze a key reaction of the sterol biosynthetic pathway, namely formation of a cyclic component from the acyclic precursors oxidosqualene and dioxidosqualene ( Fig. 1). OSCs may be regarded as phylogenetic markers insofar as they form a variety of cyclic triterpenoids in plants, whereas their only cyclization product in nonphotosynthetic eukaryotes such as animals, yeast, and other fungi is lanosterol (1). During the last 20 years studies on OSCs focused on several biochemical, molecular biological, and cell biological aspects.Hundreds of inhibitors were synthesized and tested for their effect on this enzyme (2-6), OSCs from different sources were characterized and purified (7-10), and genes encoding these proteins in various species were cloned and sequenced (11)(12)(13)(14)(15). During these studies, however, the important question as to the subcellular localization of this enzyme was surprisingly ignored. This aspect is essential because localization of enzymes involved in the sterol biosynthetic pathway may contribute greatly to the understanding of coordination and regulation of this pathway and of sterol traffic among organelles (16 -19).Subcellular localization of yeast OSC, which is encoded by the ERG7 gene, stimulated our interest not only because Erg7p is one of the most important enzymes of sterol biosynthesis that has not been localized so far, but also because targeting of the protein to its proper cellular environment may help to explain its mode of action and to design new inhibitors of OSC. As an example, we reported recently that some OSC inhibitors that undergo metabolic transformations in the yeast exhibit different effects because of different subcellular distribution of target protei...

CD is confirmed to be more prevalent in female than in male (F:M = 1.8) but, in DQ2/DQ8 negative patients, we found an unexpected male excess (F:M = 0.7). Moreover, only the inheritance of a paternal DQ2 haplotype led to a daughters predominance. These data show a role of HLA genes on the disease sex bias and suggest a possible different effect of parent-specific epigenetic modifications in the two genders.

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