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Abstract: Background: Adverse pregnancy outcomes are more frequent in celiac than in non-celiac women. Aims: To investigate a possible role of genetic prothrombotic variants in early pregnancy loss of celiac women. Methods: Thirty-nine celiac women who had experienced early pregnancy losses (at least two losses within the first 3 months of pregnancy), and 72 celiac women with a history of one or more normal pregnancies and no pregnancy loss (controls) entered the study, at the moment of diagnosis for celiac disease. A clinical history was obtained from each woman. DNA from leukocytes was tested for: factor V Leiden (mutation G1691A), factor V R2 (H1299R), factor II (G20210A), methylenetetrahydrofolate reductase (MTHFR) (C677T and A1298C), beta-fibrinogen (−455 G>A), PAI-1 alleles 4G/5G, factor XIII (V34L), and HPA-1 (L33P). Results: Age at diagnosis was significantly higher (p =0.002) in the celiac women with pregnancy losses than in controls. Of the gene variants studied, the allelic frequency of 4G variant of PAI-1, and the frequency of mutant genotypes were significantly more frequent in the group of celiac women with early pregnancy loss (p =0.00003 and 0.028, respectively). Surprisingly, the beta-fibrinogen −455 G>A genotype distribution (but not the allelic frequency of the variant allele) significantly differed between the two groups, since variant genotypes were more frequent in the control group (p =0.009). Conclusion: The 4G variant of the PAI-I gene may predispose to miscarriage a subset of celiac women; these data should be verified on larger populations. [Copyright &y& Elsevier]

Abstract: Objectives: Polymorphisms in the major histocompatibility complex class I chain-related gene A may influence its binding to the Natural Killer Cell Receptor G2D (NKG2D). We looked for polymorphisms in major histocompatibility complex class I chain-related gene A exon 5 and in Human Leukocyte Antigen (HLA)-DQ/DR in adult coeliac disease patients to determine whether they affected coeliac disease phenotypes. Methods: Adult coeliac disease patients with (n =98) and without (n =93) gastrointestinal symptoms (gastrointestinal symptoms+/gastrointestinal symptoms−) and 108 control subjects from Campania (Italy) were characterized by Polymerase Chain Reaction (PCR) sequence specific oligonucleotide followed by PCR sequence specific primer assays for HLA DQ/DR, and by PCR followed by capillary electrophoresis for major histocompatibility complex class I chain-related gene A exon 5 polymorphisms. Immunoglobulin A (IgA) anti-transglutaminase antibodies were also evaluated by immunosorbent assay. Results: Five different major histocompatibility complex class I chain-related gene A alleles were detected in both coeliac disease patients and control subjects. The major histocompatibility complex class I chain-related gene A 5.1 allele occurred more frequently in patients than in controls (p <0.05), and the major histocompatibility complex class I chain-related gene A 5.1/5.1 homozygous genotype increased the risk of gastrointestinal symptoms− coeliac disease (OR=2.79, 95% CI 1.15–6.79). Gastrointestinal symptoms− coeliac disease patients bearing major histocompatibility complex class I chain-related gene A 5.1/5.1 alleles showed lower anti-transglutaminase levels (18U/L) than the gastrointestinal symptoms+ coeliac disease patients (35U/L). HLA-DQ2/DQ8 genotypes did not differ between gastrointestinal symptoms+ and gastrointestinal symptoms− coeliac disease, although DQ8 tended to be more frequent in gastrointestinal symptoms− coeliac disease (11.7%) than in gastrointestinal symptoms+ coeliac disease (6%). Conclusions: Our study shows that a double dose of the major histocompatibility complex class I chain-related gene A 5.1 allele could predispose to the onset of gastrointestinal symptoms− coeliac disease. We can hypothesize that a lower level of immunological involvement in gastrointestinal symptoms− coeliac disease patients is associated with absence of gastrointestinal symptoms. This test could represent a second step in the genetic typing of high-risk subjects such as first-degree relatives of coeliac disease patients positive for the DQ2/DQ8 molecule. [Copyright &y& Elsevier]

Abstract: Background: Fatigue is common in celiac disease. L-Carnitine blood levels are low in untreated celiac disease. L-Carnitine therapy was shown to improve muscular fatigue in several diseases. Aim: To evaluate the effect of L-carnitine treatment in fatigue in adult celiac patients. Methods: Randomised double-blind versus placebo parallel study. Thirty celiac disease patients received 2g daily, 180 days (L-carnitine group) and 30 were assigned to the placebo group (P group). The patients underwent clinical investigation and questionnaires (Scott-Huskisson Visual Analogue Scale for Asthenia, Verbal Scale for Asthenia, Zung Depression Scale, SF-36 Health Status Survey, EuroQoL). OCTN2 levels, the specific carnitine transporter, were detected in intestinal tissue. Results: Fatigue measured by Scott-Huskisson Visual Analogue Scale for Asthenia was significantly reduced in the L-carnitine group compared with the placebo group (p =0.0021). OCTN2 was decreased in celiac patients when compared to normal subjects (−134.67% in jejunum), and increased after diet in both celiac disease treatments. The other scales used did not show any significant difference between the two celiac disease treatment groups. Conclusion: L-Carnitine therapy is safe and effective in ameliorating fatigue in celiac disease. Since L-carnitine is involved in muscle energy production its decreased absorption due to OCTN2 reduction might explain muscular symptoms in celiac disease patients. The diet-induced OCTN2 increase, improving carnitine absorption, might explain the L-carnitine treatment efficacy. [Copyright &y& Elsevier]

Abstract: Background.: The development of cranial proportions is the result of genetic, embriogenetic and environmental factors. Coeliac disease is a genetically inherited disease that is frequently diagnosed in adulthood in individuals, in whom the disease runs unidentified for years and can affect child growth from the moment of dietary gluten introduction up to the moment of gluten withdrawal following diagnosis. Data on the effects of gluten on craniofacial development in coeliac children are not available. Aim.: The aim of the present study is to evaluate gluten-related effects on face development in patients with undiagnosed coeliac disease and their clinical relevance. Methods.: The study was a prospective, multivariate analysis. Face photographs of adult patients with coeliac disease and healthy controls were marked at six reference points and distances and the ratios among distances were measured by computer program software. Results.: The main finding of the study is that Caucasian Mediterranean adult coeliac individuals tend to have a peculiar aspect of the face characterised by a larger forehead when compared to general population controls. Conclusion.: The craniofacial morphology of patients with coeliac disease reveals an altered pattern of craniofacial growth. This is the first report of alterations of craniofacial development in coeliac disease. This alteration is a clinical sign that should be included among the extraintestinal manifestation of coeliac disease. It has a frequency comparable to other signs or symptoms such as anaemia and short stature and is a better predictor of coeliac disease than other signs such as recurrent aphthous stomatitis, recurrent abortion and dental enamel hypoplasia. A large forehead is a sign easily evident visually or with very simple measurements; computer analysis is not required for the general practitioner. This sign along with the presence of other clinical signs and symptoms, should alert a physician to test a patient for coeliac disease. [Copyright &y& Elsevier]

Abstract: The paper deals with a viewpoint on the relationship between the drug industry and the medical world taking inspiration from the history of the discovery of Helicobacter pylori as a pathogenic agent in peptic disease. [Copyright &y& Elsevier]