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Giacomo Carlo Sturniolo

Publications and source records attributed to Giacomo Carlo Sturniolo.

At least 19 recordsLinked to original sources
PubMed2006

Calprotectin and lactoferrin in the assessment of intestinal inflammation and organic disease.

BACKGROUND AND AIMS: Calprotectin and lactoferrin are specific neutrophil-derived proteins, which can be measured in the feces because they are released by cells in inflammatory conditions. We evaluated the efficacy of calprotectin and lactoferrin in detecting organic disease as assessed by colonoscopy. METHODS: The study comprised 144 patients undergoing colonoscopy for lower gastrointestinal symptoms (abdominal pain, altered bowel habits, and bloody stools) (67), or inflammatory bowel disease activity, or surveillance for dysplasia (77). A single stool sample was assayed for calprotectin and lactoferrin. The proportion of patients correctly diagnosed with each test and the relationship with endoscopic and histological findings were measured. RESULTS: Fecal excretion of calprotectin significantly correlated with the finding of colonic inflammation at endoscopy, both in ulcerative colitis and in Crohn's disease (p<0,001 and p<0,008, respectively), while lactoferrin excretion significantly correlated with histological inflammation (p=0.001 and p=0.009 respectively). Recommended cut-off values need to be adjusted in the inflammatory bowel disease group. Overall sensitivity, specificity, positive predictive value, and diagnostic efficacy were 78, 83, 86, and 80% for calprotectin and 80, 85, 87, and 81% for lactoferrin, respectively. CONCLUSIONS: Fecal calprotectin and lactoferrin appear to be equally recommendable as inflammatory disease markers in patients with lower gastrointestinal symptoms. Both tests are needed to accurately discriminate activity in inflammatory bowel disease patients.

Adolescent↗
PubMed2006

Different neurological outcome of liver transplantation for Wilson's disease in two homozygotic twins.

Wilson's disease is a genetic disorder characterized by accumulation of copper in many organs and tissues. Phenotypic manifestations are wide-ranging from neuropsychiatric disorders, to severe liver disease requiring liver transplantation. Clinical presentation is not often related to the genetic defect and siblings may have different type of disease. Liver transplantation is indicated for all patients with Wilson's disease and decompensated liver cirrhosis unresponsive to medical therapy, but its efficacy in resolving the neurological symptoms is still controversial, because as far now, very different outcomes have been reported. We describe here on the exceptional case of two homozygotic twins, both with liver cirrhosis due to Wilson's disease, one of them with severe neuropsychiatric involvement, who both underwent liver transplantation and subsequently had very different outcome despite same genetic background. The presence of neurological clinical manifestations in Wilson's disease should recommend caution indicating liver transplantation, because irreversible brain damage may exist.

Adult↗
PubMed2006

Expression of costimulatory molecule CD80 in colonic dysplasia in ulcerative colitis: an immunosurveillance mechanism against colorectal cancer?

BACKGROUND AND AIMS: Ulcerative colitis is an established risk factor for colorectal cancer but dysplasia reports are much more frequent than invasive neoplasm diagnosis. The effective activation of T lymphocytes that provide antitumor surveillance requires the presence of costimulation molecules such as CD80 and CD86 on the surface of antigen-presenting cells. The aim of our study was to verify the presence of an in vivo immunosurveillance mechanism in the early stages of colon tumorigenesis. PATIENTS AND METHODS: Expression of CD80, CD86, and IFN-gamma in the colonic mucosa of 21 consecutive ulcerative colitis (UC) patients was quantified using reverse transcription polymerase chain reaction. After a 7-year follow-up period, we reviewed the histology of all surveillance colonoscopy specimens for colonic dysplasia. Correlation, frequency, and survival analyses were performed. RESULTS: CD80 was detectable in seven patients while expression of CD86 and IFN-gamma was evident in all patients. Histology confirmed the presence of dysplasia in eight patients. Patients who had dysplasia showed higher CD80 levels compared to those without dysplasia (p=0.02). Survival analysis demonstrated that cumulative dysplasia rates of CD80-positive patients were significantly higher than those of CD80-negative patients (p=0.04). CONCLUSION: Even if partially limited by a relatively small sample size, our study seems to show an association between CD80 expression and colonic dysplasia in UC patients that may suggest a role for CD80 in the immunosurveillance against colorectal cancer in this early stage of tumorigenesis. On the contrary, CD86 seems to be involved in the inflammatory pathogenesis of UC.

Actins↗
PubMed2005

Efficacy of zinc supplementation in preventing acute hepatitis in Long-Evans Cinnamon rats.

OBJECTIVES: Long-Evans Cinnamon (LEC) rats are characterized by an abnormal hepatic deposition of copper (Cu) due to a lack of the Cu-transporter P-type adenosine triphosphatase: accordingly, the strain is a good animal model of Wilson's disease. The effect of oral zinc (Zn) acetate treatment on the development of acute hepatitis and the biochemical parameters of Cu-induced liver damage was studied in 5-week-old LEC rats (n=52). METHODS: Rats receiving 50 or 80 mg/ml/day Zn acetate by gavage and control rats receiving a daily dose of glucose solution 0.02 g/ml by gastric intubation were killed at 1, 2 or 8 weeks after the start of treatment. RESULTS: Treatment with Zn acetate resulted in the prevention of acute hepatitis: 10 of the 13 untreated rats developed signs and symptoms compatible with acute hepatitis between the 6th and 7th week of treatment. Tissue metallothionein (MT) significantly increased in the treated rats and positively correlated with Zn concentrations within the liver. Control rats had a significantly higher iron concentration in the liver and kidneys compared with supplemented rats, after both short- and long-term experiments. 8-hydroxy-2'-deoxyguanosine amounts were significantly lower in untreated rats. CONCLUSIONS: Zn acetate prevents acute hepatitis, by increasing tissue MT concentrations, reducing Cu absorption and interfering with Fe metabolism.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2004

Evaluation of MT expression and detection of apoptotic cells in LEC rat kidneys.

To confirm our previous observations on the effectiveness of long term treatment with Zn on Long-Evans Cinnamon (LEC) rats, we extended these studies determining the effects of Zn on trace elements, metallothionein (MT) concentrations and immunolocalization, and on the levels of both MT-1 and MT-2 mRNAs in the LEC rat kidneys. We also localized the renal cells that had chromatin condensation and nuclear fragmentation typical of apoptosis. The results demonstrate that the amount of Zn increased in the treated rats with respect to both untreated and basal rats. In the treated rats the amount of Cu and Fe was similar to that of the basal rats. MT concentrations did not change either with or without Zn treatment, but were higher than the basal group. However, if we consider the percentage of oxidized MT (MTox), we note that Zn treatment is very effective in reducing this value. MTox is not able to bind metals, so it does not perform a "scavenger" function. Moreover, quantification of mRNA indicates that the MT-1 isoform was significantly higher than the MT-2 isoform following Zn treatment. Untreated group sections showed a confocal fluorescent signal that highlighted the irregular nuclei and small apoptotic bodies. The intensity and quantity of fluorescence decreased in the treated group sections. These findings suggest that, in LEC rats, Zn may contribute to cytoprotection through the regulation of MT expression which may provide a cellular defence strategy in response to DNA damage.

Animals↗
PubMed2004

Whipple's disease.

Explore the source record for details and available documents.

Endoscopy, Gastrointestinal↗
PubMed2004

Oxidative DNA damage in the mucosa of ulcerative colitis increases with disease duration and dysplasia.

BACKGROUND: Chronic inflammation may contribute to cancer risk through the accumulation of specific products as a result of DNA damage. The role of free radical mediated oxidative DNA damage during inflammation was determined in patients with ulcerative colitis by measuring 8-hydroxydeoxyguanosine (8-OHdG). METHODS: Patients with ulcerative colitis were compared according to age, gender, duration and extent of disease, endoscopic and histologic activity, presence or absence of dysplasia/cancer, and biochemical parameters of inflammation. Patients with sporadic colon cancer and irritable bowel syndrome served as controls. Levels of 8-OHdG were assessed by high pressure liquid chromatography with electrochemical detection (mean number of adducts/10(5) dG residues). RESULTS: Patients with ulcerative colitis and dysplasia had significantly higher mucosal 8-OHdG concentrations (P = 0.011). 8-OHdG concentrations were significantly higher in older patients (P = 0.010), patients with long-standing disease (P = 0.015), active endoscopic (P = 0.006) or histologic disease (P = 0.003). Covariance analysis showed significant effect of dysplasia on 8-OHdG levels: values higher than 100 adducts/10(5) dG had a diagnostic value of 80.9% (SE 6.2%). CONCLUSIONS: Oxidative DNA damage accumulates with the duration of the disease in ulcerative colitis reaching maximal increase if dysplastic lesions are found with possible implications for mutagenic and carcinogenic progression.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Metallothionein-1 and metallothionein-2 gene expression and localisation of apoptotic cells in Zn-treated LEC rat liver.

The aims of the present work were to determine the effect of long-term treatment with zinc (Zn) on metallothionein (MT) concentrations and to study the levels of both MT-1 and MT-2 mRNAs in Long-Evans Cinnamon (LEC) rat liver. We also identified apoptotic cells comparing two cytochemical techniques. Thirteen rats received 50 mg zinc acetate daily by gavage, 13 rats received no treatment, and both groups were killed after 60 days. Finally four rats were killed 35 days after birth (T(0)). The results demonstrate that the Zn-treated group had higher levels of MT than both the untreated and basal ones. Quantification of mRNA indicates that the level of the Zn-treated group was significantly higher than the untreated group. Confocal fluorescent staining with monoclonal antibody (Mab) against single-strand DNA localised the hepatic cells that had chromatin condensation and nuclear fragmentation typical of apoptosis, especially in the untreated group sections. The intensity and quantity of fluorescence decreased in both the treated and basal groups. The higher sensitivity of Mab staining compared to TUNEL, which revealed both apoptotic and necrotic cells, reflects the different action mechanism of the two techniques. These findings confirm, in LEC rats, the important role of Zn in cellular protection in relation to MT expression and apoptotic processes as cellular responses to DNA damage by free radicals.

Administration, Oral↗
PubMed2003

Relationship between IL-18 and sICAM-1 serum levels in patients affected by coeliac disease: preliminary considerations.

OBJECTIVES: Cytokine production from activated T cells play a pathogenetic role in mucosal lesions of coeliac disease (CD). Active interleukin (IL)-18 is expressed in the small intestinal mucosa in CD but not in healthy controls. IL-18 enhances intercellular adhesion molecule-1 (ICAM-1) expression. We analyzed IL-18 serum levels in CD patients before and after gluten-free diet and the possible correlation with soluble ICAM-1 (sICAM-1) serum levels. METHODS: The study comprises ten CD patients before and after gluten free diet and ten healthy controls. Serum IL-18 and sICAM-1 levels were assayed by immunoenzymatic methods. RESULTS: Serum IL-18 and sICAM-1 levels were significantly higher in patients with CD before diet with respect to healthy controls (P<0.05), with a highly significant correlation between the two parameters (Rho=0.800, P=0.0167). Gluten free diet significantly reduces IL-18 and sICAM-1. CONCLUSION: Our findings show that IL-18 serum concentrations correlated with the clinical status of CD patients suggesting a role for this cytokine in the pathophysiology of this disease.

Adolescent↗
PubMed2003

Effect and possible role of Zn treatment in LEC rats, an animal model of Wilson's disease.

The effect of oral zinc (Zn) treatment was studied in the liver, kidneys and intestine of Long-Evans Cinnamon (LEC) rats in relation to metals interaction and concentration of metallothionein (MT) and glutathione (GSH). We also investigated the change in the activity of antioxidant enzymes and determined the biochemical profile in the blood and metal levels in urine. We showed that the Zn-treated group had higher levels of MT in the hepatic and intestinal cells compared to both untreated and basal groups. Tissue Zn concentrations were significantly higher in the Zn-treated group compared to those untreated and basal, whereas Cu and Fe concentrations decreased. The antioxidant enzyme activities in the Zn-treated group did not change significantly with respect to those in the basal group, except for hepatic glutathione peroxidase activity. Moreover, the biochemical data in the blood of Zn-treated group clearly ascertain no liver damage. These observations suggest an important role for Zn in relation not only to its ability to compete with other metals at the level of absorption in the gastrointestinal tract producing a decrease in the hepatic and renal Cu and Fe deposits, but also to MT induction as free radical scavenger.

Animals↗
PubMed2003

Zinc treatment prevents lipid peroxidation and increases glutathione availability in Wilson's disease.

Oxidative and reductive mechanisms are important in Wilson's disease. In this study, we sought to evaluate tissue levels of glutathione and cysteine, an important detoxification system, and of malondialdehyde, a marker of lipoperoxidation, in patients with Wilson's disease receiving penicillamine or zinc treatment, in comparison with patients with chronic liver disease of different origin. Concentrations of cysteine, reduced/oxidized glutathione, malondialdehyde, zinc, and copper were determined (with the use of high-pressure liquid chromatography, fluorimetry and atomic-absorption spectrophotometry) in liver-biopsy specimens from 24 patients with Wilson's disease (18 treated with zinc, 6 with penicillamine), 34 patients with chronic viral hepatitis, and 10 patients with alcoholic liver disease. In patients with Wilson's disease, the concentration of reduced glutathione was lower than that in patients with viral hepatitis and as high as that in subjects with alcoholic liver damage. The cysteine level was significantly lower than those in the control groups, and the percentage of oxidized glutathione/total glutathione was higher than that in viral or alcoholic disease. Malondialdehyde levels were low, but when zinc- and penicillamine-treated patients were considered separately, only the former had low malondialdehyde levels. Zinc-treated patients had higher concentrations of reduced glutathione and a lower percentage of oxidized glutathione. In summary, patients with Wilson's disease have relevant glutathione depression, with low levels of reduced glutathione and cysteine and high concentrations of oxidized glutathione: This is prevented by zinc administration, which inhibits lipid peroxidation and increases glutathione availability.

Adolescent↗
PubMed2003

Role of CD40 and B7 costimulators in inflammatory bowel diseases.

We analyse the costimulating role of CD40/CD40 ligand and B7/CD28 in inflammatory bowel diseases (IBD) as a potential target of antibody therapy. CD40, expressed by lamina propria B lymphocytes in gut mucosa, interacts with CD40 ligand on T cell. This interaction is implicated in the pathogenesis of IBD. In some animal models of colitis the anti-CD40L therapy demonstrated to be effective. Phase II trials on Crohn's disease are ongoing. B7.1 and B7.2, expressed by macrophages, interact with CD28, on T cell. B7.2 resulted implicated in ulcerative colitis, determining a Th2 pattern, whereas B7.1, a major Th1 stimulator, could be involved in Crohn's disease. In some animal models of colitis anti-B7.1, but not anti-B7.2, was effective. Anti B7 therapy was not yet tested in humans.

Animals↗
PubMed2002

Metallothionein and antioxidant enzymes in Long-Evans Cinnamon rats treated with zinc.

The Long-Evans Cinnamon (LEC) rat is a mutant animal model for Wilson's disease. It is known that an abnormal accumulation of Cu and Fe in the liver and low concentrations of both ceruloplasmin and Cu in the serum occur in these rats. The accumulation of Cu is explained by the defective expression of the Cu-transporting P-type ATPase gene, homologous to the gene for Wilson's disease (ATP7B). The aim of this work was to clarify the action mechanism of Zn, and to verify the role that this metal plays in LEC rats in short-term treatment experiments (1 and 2 weeks) on concentrations of Cu, Zn, Fe, metallothionein (MT), 8-hydroxy-2'-deoxyguanosine (oh(8)dG) and on the activity of antioxidant enzymes. It is well known that Zn induces MT and has the ability to prevent redox-active metals, Cu and Fe, binding to and causing oxidative damage at active sites of Zn metalloenzymes and nonspecific binding sites on proteins. Zn administration reduces Cu and Fe transport from mucosal to serosal intestinal sides through competitive mechanisms. Our findings show that treatment with zinc acetate increases tissue Zn and MT contents and decreases Cu and Fe concentrations in the liver and kidneys, even if hepatic Zn and MT concentrations decrease with treatment period. Induction of MT synthesis by Zn contributes to the reduction in free radicals produced by Cu and Fe. We also observed that the superoxide dismutase (SOD)activity in liver decreases with treatment duration in association with the Cu and Fe liver decrease. However, the SOD activity in kidney increases in untreated rats at 2 weeks relative to those untreated for 1 week.

Animals↗
PubMed2002

Interactions between Zn and Cu in LEC rats, an animal model of Wilson's disease.

The effect of oral Zn treatment was studied in the liver and kidneys of 26 male Long-Evans Cinnamon (LEC) rats (mutant animals, 5 weeks old) in relation to both the interaction between Zn and Cu and the localisation and concentration of metallothionein (MT). Rats receiving 80 mg zinc acetate daily by gavage and control rats receiving no treatment were killed after 1 or 2 weeks. By immunohistochemical and analytical chemical techniques we revealed that treated rats had higher levels of MT in the hepatic and renal cells compared to untreated ones. Tissue Zn concentrations were significantly higher in treated rats compared to untreated whereas Cu concentrations decreased in the liver and kidneys as indicated by analytical chemical analyses. MT levels also decreased with treatment period. A histochemical procedure, obtained using autofluorescence of Cu-metallothioneins, confirms these findings: after 2 weeks, the signal decreased in both the liver and kidney sections. This gives a greater understanding of the mechanism of Cu metabolism in the two tissues considered. These results suggest that Zn acts both to compete for absorption on the luminal side of the intestinal epithelium and to induce the synthesis of MT.

Animals↗
PubMed2002

Effect of zinc supplementation on intestinal permeability in experimental colitis.

Increased small-intestine permeability has been documented in experimental colitis in the rat. Zinc supplementation improves mucosal repair in patients with diarrhea, as well as paracellular permeability in malnourished guinea pigs. In this study, we sought to evaluate the effect of zinc supplementation on small-and large-intestine tight junctions in rats with acute colitis. Rats were given zinc at a dosage of 2 or 30 mg/kg body wt or glucose by gavage starting 3 days before colitis was induced through the intrarectal administration of dinitro-benzene-sulfonic acid and for 7 days thereafter. We evaluated small-intestine permeability by the number of tight junctions showing extravasation of lanthanum under electron microscopy. Low-dose zinc affected none of the examined parameters of colitis severity. Rats given high-dose zinc showed colitis of similar macroscopic and biochemical severity. However, zinc-treated rats weighed more than unsupplemented ones. The number of perfused tight-junction complexes was significantly higher in animals with colitis than in controls and in the rats with colitis given high-dose zinc. Zinc may regulate tight-junction permeability, with possible implications for healing processes in inflammatory bowel diseases.

Animals↗
PubMedDate not supplied

The role of costimulatory molecules CD80 and CD86 and IFNgamma in the pathogenesis of ulcerative colitis.

Several studies showed that costimulatory signals on antigen presenting cells are up-regulated in inflammatory bowel disease. We quantified the expression of CD80, CD86, and IFNgamma in colonic mucosa of patients affected by ulcerative colitis and correlated it with clinical and biochemical parameters to identify the context of this up regulation. We enrolled 21 patients affected by ulcerative colitis and 6 healthy subjects. We evaluated for each patient gender, age, duration of disease, clinical, endoscopic and histologic disease activity index, medical therapy, ESR, serum CRP, WBC, and serum al-acid glycoprotein. CD80, CD86, and IFNgamma expression in the colonic mucosa was quantified using reverse transcription polymerase chain reaction. Statistical analysis was performed using Mann-Whitney U test and Spearman's rank correlation test. Significance was set at P < 0.05. CD80 was detectable in seven patients, while CD86 and IFNgamma expression was evident in all UC patients. CD80 and CD86 were not detectable in control specimens. Colonic CD80 expression was correlated to the age of the patients. CD86 expression showed an inverse correlation with duration of disease and a direct correlation with serum CRP levels and histologic grade of disease activity. IFNgamma was not correlated with any of the examined parameter. Our study confirms a major role in ulcerative colitis pathogenesis for CD86 which correlates with histologic grade of disease and with serum CRP levels, and its upregulation seems to be higher at the beginning of the disease. In "in vivo" conditions IFNgamma may not be the only factor responsible for CD86 up-regulation in the ulcerative colitis colonic mucosa.

Adolescent↗