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Dario Conte

Publications and source records attributed to Dario Conte.

29 records · Page 2Linked to original sources
PubMed2003

Oxidative stress-mediated down-regulation of rat hydroxyacid oxidase 1, a liver-specific peroxisomal enzyme.

Hydroxyacid oxidase 1 (Hao1) is a liver-specific peroxisomal enzyme that oxidizes glycolate to glyoxylate with concomitant production of H2O2. In Hao1 messenger RNA (mRNA), an iron-responsive element (IRE) homologous to the sequence recognized by iron regulatory proteins (IRP), key regulators of iron homeostasis, is present, but the involvement of iron in Hao1 regulation remains unclear. In this study, we found a reduction of Hao1 mRNA content in livers of rats with chronic dietary iron overload, which showed decreased IRP activity and higher ferritin expression as expected, but also induction of heme oxygenase (HO-1), a marker of oxidative damage, and lipid peroxidation. Hao1 mRNA levels were not altered significantly in livers of rats administered doses of iron sufficient to induce ferritin expression and to repress IRP activity, but not to activate HO-1 and to promote lipid peroxidation, as well as in the liver of iron-deficient rats. These observations were not consistent with a post-transcriptional down-regulation of Hao1 by iron through the IRE/IRP pathway and suggested an effect of reactive oxygen species (ROS). Indeed, a marked decrease of Hao1 mRNA was observed in the liver of rats subjected to oxidative stress induced by either glutathione depletion or postischemic reperfusion. Nuclear run-on analysis showed an effect of ROS at the transcriptional level. In conclusion, down-regulation of Hao1 expression during oxidative stress may provide a mechanism to prevent excessive H2O2 formation in liver peroxisomes and may represent the prototype of a poorly recognized but potentially relevant response to oxidative injury involving down-regulation of ROS-producing enzymes.

Alcohol Oxidoreductases↗
PubMed2003

Circulating ghrelin levels in celiac patients.

OBJECTIVE: Ghrelin, the gut-brain peptide, recently identified as the natural endogenous ligand for growth hormone secretagogue receptors, exerts various endocrine and nonendocrine effects, including the control of energy homeostasis and food intake, but its possible relevance in malabsorption syndromes is unknown. Therefore, the aim of this study was to evaluate circulating ghrelin levels in adults with untreated and treated celiac disease (CD) and, for comparison, in healthy subjects. METHODS: Fasting serum ghrelin levels were measured in 30 consecutive patients with newly diagnosed CD, 13 celiac patients successfully treated with a gluten-free diet (GFD), and 30 healthy controls. RESULTS: Ghrelin levels were abnormally high in patients with active CD compared with controls (297 +/- 17.6 vs 218 +/- 15.2 pmol/L, p<0.01) and correlated positively with intestinal mucosal lesion severity (rs=0.444, p<0.02). In the successfully GFD-treated patients, ghrelin values were normal compared with controls (233 +/- 22.0 vs 218 +/- 15.2 pmol/L, ns) and, moreover, correlated negatively with body mass index (r=-0.632, p=0.02), unlike in the untreated patient group (r=-0.263, ns). CONCLUSION: High ghrelin levels characterized our series of adult patients with newly diagnosed CD and correlated significantly with the degree of severity of intestinal mucosal lesions. This is the first evidence of a relationship between ghrelin and inflammatory processes, but the mechanisms involved are still unclear. Furthermore, our findings suggest that an interplay of hormonal, metabolic, and nutritional factors could influence ghrelin secretion under pathophysiological circumstances.

Adolescent↗
PubMed2002

Celiac sprue.

Explore the source record for details and available documents.

Adult↗
PubMed2002

Updated definitions of healthy ranges for serum alanine aminotransferase levels.

BACKGROUND: Serum alanine aminotransferase (ALT) activity, the variable most commonly measured to assess hepatic disease, fails to identify many patients with hepatic injury. Current standards for "normal" ALT level were defined by using populations that included persons with subclinical liver disease. OBJECTIVE: To update definitions of healthy ranges for serum ALT level. DESIGN: Retrospective cohort study. SETTING: A university hospital in Milan, Italy. PARTICIPANTS: 6835 persons who were first-time blood donors from 1995 through 1999, were negative for anti-hepatitis C virus (HCV), and had no contraindications to donation and 209 persons who attempted to donate blood from 1990 through 1999 but were found to have anti-HCV antibodies. Of the latter group, 131 had HCV viremia. MEASUREMENTS: Univariate and multivariate analyses examined associations between clinical and laboratory factors and ALT levels. Healthy ranges for ALT were computed from the population at lowest risk for liver disease. Sensitivity and specificity of healthy ALT ranges were evaluated in the donors with HCV antibodies, of whom 133 had liver biopsy. RESULTS: Serum ALT activity was independently related to body mass index and to laboratory indicators of abnormal lipid or carbohydrate metabolism. Updated upper limits (for men, 500 nkat/L [30 U/L]; for women, 317 nkat/L [19 U/L]) were lower than current limits (for men, 667 nkat/L [40 U/L]; for women, 500 nkat/L [30 U/L]) and, during 6-month follow-up, showed superior sensitivity in identifying participants with HCV viremia (sensitivity, 76.3% [95 % CI, 69.1% to 83.6%] vs. 55% [CI, 46.4% to 63.5%]). The related tradeoff in specificity was acceptable (88.5% [CI, 79.2% to 94.6%] vs. 97.4% [91% to 99.7%]). The increased sensitivity targeted patients with minimal to mild histologic lesions. CONCLUSION: In patients with chronic HCV infection or nonalcoholic fatty liver disease, revision of normal limits for ALT level is advisable.

Alanine Transaminase↗
PubMed2002

Age at infection affects the long-term outcome of transfusion-associated chronic hepatitis C.

Before the introduction of hepatitis C virus (HCV) screening for blood donors, the risk of acquiring HCV infection as a result of a transfusion was about 10%. The aim of this study was to assess the frequency and rate of progression to cirrhosis in patients with transfusion-associated chronic HCV infection and identify possibly negative prognostic factors. Of 2477 consecutive patients with clinical or laboratory evidence of liver disease, 392 (16%) were anti-HCV- and HCV-RNA-positive, had anamnestic evidence of a single and precisely dated transfusion event, and showed no other causes of chronic liver disease; 268 (68%) underwent ultrasound-guided liver biopsy and were enrolled in the study. After a mean interval of 18.4 years, 54 patients (20.1%) had cirrhosis, which multivariate analysis showed to be independently associated with the duration of follow-up, age at infection and at the time of liver biopsy, and serum alanine aminotransferase levels at biopsy. The time necessary to have a 50% probability of developing cirrhosis in patients aged 21-30, 31-40, and more than 40 years was 33, 23, and 16 years, respectively. In comparison with those aged 20 years or less at infection, the risk ratio of developing cirrhosis over a period of 30 years for patients aged 21-30 and at least 31 years at infection was, respectively, 4.51 (95% confidence interval, 1.03-19.76) and 12.29 (95% confidence interval, 3.06-49.40). In patients with transfusion-associated chronic hepatitis C, the risk of cirrhosis is related to age at infection and disease activity. Our findings suggest that an aggressive therapeutic approach should be adopted in patients infected by HCV at an older age to prevent the progression to end-stage liver disease.

Adolescent↗
PubMed2002

Tissue transglutaminase antibodies in patients with end-stage heart failure.

OBJECTIVE: For celiac disease (CD), screening a trend has recently emerged to measure tissue transglutaminase antibodies (tTGA) by immunoassays instead of the more laborious endomysial antibodies (EmA), as they recognize the same target, tissue transglutaminase (tTG). However, a high rate of false-positive results has been reported in some patient series with diseases known to be associated with CD. Moreover, tTG is a ubiquitous, multifunctional enzyme, overexpressed in experimental models of heart failure. Therefore, we assessed the specificity of tTGA assays in a large series of EmA-negative patients with end-stage heart failure. METHODS: We studied 288 patients with end-stage heart failure and 60 blood donors. No subject had clinical evidence of CD or IgA deficiency, and all were EmA negative. Serum IgA and IgG tTGA were measured by means of commercial kits using as substrate, either guinea pig or recombinant human tTG. Blocking studies and Western blots were also performed using recombinant human tTG. RESULTS: All blood donor sera were IgA tTGA negative. IgA tTGA positivity was observed in 47.6% and 49.1% of patients with heart failure using, respectively, guinea pig tTG and recombinant human tTG as substrates. Preincubation of positive sera with recombinant human tTG resulted in 81% blocking of IgA tTGA in immunoassay. Western blot analysis confirmed the presence of antibodies against recombinant human tTG. IgA tTGA-positive sera were also IgG tTGA positive. CONCLUSIONS: IgA and IgG tTGA occur in a large number of EmA-negative patients with end-stage heart failure, and their presence is unlikely to be caused by concomitant CD.

Adult↗
PubMedDate not supplied

Transferrin receptor 1 (TfR1) and putative stimulator of Fe transport (SFT) expression in iron deficiency and overload: an overview.

Transferrin Receptor 1 (TfR1) and putative Stimulator of Fe Transport (SFT) represent two different proteins involved in iron metabolism in mammalian cells. The expression of TfR1 in the duodenum of subjects with normal body iron stores has been mainly localized in the basolateral portion of the cytoplasm of crypt cells, supporting the idea that this molecule may be involved in the sensing of body iron stores. In iron deficiency anemia TfR1 expression demonstrated an inverse relationship with body iron stores as assessed by immunohistochemistry with anti-TfR1 antibodies. In iron overload, TfR1 expression in the duodenum differed according to the presence or absence of the C282Y mutation in the HFE gene, being increased in HFE-related hemochromatosis and similar to controls in non-HFE-related iron overload. SFT is characterized by its ability to increase iron transport both through the transferrin dependent and independent uptake, and could thus affect iron absorption in the intestine. Immunohistochemistry using anti-SFT antibodies which recognize a putative stimulator of Fe transport of approximately 80 KDa revealed a localization of this protein in the apical part of the cytoplasm of enterocytes localized at the tip of the villi. The expression of the protein recognized by these antibodies was increased in iron deficiency, as well as in patients carrying the C282Y HFE mutation. Thus, the increased expression of both proteins only in patients with HFE-related hemochromatosis suggests that other factors should be involved in determining non-HFE-related iron overload.

Animals↗