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Biomedical subjects

G C Sturniolo

Publications and source records attributed to G C Sturniolo.

At least 19 recordsLinked to original sources
PubMed1999

Genetic analysis in Italian families with inflammatory bowel disease supports linkage to the IBD1 locus--a GISC study.

Epidemiological studies suggest that inherited factors influence susceptibility to inflammatory bowel disease (IBD), and some candidate loci have been described. In order to verify whether the same loci are responsible for predisposition to IBD in our population, we carried out a linkage study in a series of 58 Italian families with Crohn's disease (CD) and ulcerative colitis (UC). HLA-DQ alleles, motilin gene, and 34 microsatellites flanking the previously described loci on chromosomes 3, 6, 7, 12 and 16 were analysed by non-parametric linkage analysis in 16 and 23 families with CD and UC, respectively, and in 19 families where CD and UC coexisted. Non parametric analysis using GENEHUNTER yielded maximum NPL scores for marker D16S408 in all IBD families combined (2.71, P = 0.003), for marker D16S419 in CD (1.97, P = 0.026) and for marker D16S514 in UC families (2.44, P = 0.007). These markers map in the previously described IBD1 region. No significant linkage was found for markers of chromosomes 3, 6, 7 and 12. The present study performed in a Southern European population provides additional support for the conclusion with the IBD1 locus has a clear role in the genetic susceptibility to IBD.

Chromosome Mapping↗
PubMed1999

Prevention of post-operative recurrence of Crohn's disease requires adequate mucosal concentration of mesalazine. Gruppo Italiano per lo Studio del Colon e del Retto.

BACKGROUND: Surgical resection of Crohn's disease is followed by early recurrence in a high percentage of patients. Mesalazine has been shown to be effective in the prevention of post-operative recurrence, but some 50% of patients under treatment recur at 3 years of follow-up. AIM: To establish whether the mucosal concentration of mesalazine might affect the development of post-operative recurrence. METHODS: Colon-ileoscopy was performed in 25 consecutive patients resected for Crohn's disease. The mean time from surgery was 14 months. After the operation, all patients were taking oral mesalazine (Asacol, 2.4 g/day). Ten patients showed signs of endoscopic recurrence (apthae, ulcers, narrowing of the lumen) in the neoterminal ileum, five of whom also showed juxta-anastomotic colonic involvement. Fifteen patients were free of recurrence. At endoscopy, four biopsies were taken from the perianastomotic area (two specimens at the ileal site and two specimens at the colonic site of the anastomosis). The specimens were weighed and immediately frozen at -80 degrees C. Mesalazine concentration (ng/mg) was measured in tissue homogenates by high- performance liquid chromatography with electrochemical detection. Fisher's exact test was used for the statistical analysis. RESULTS: The mean value of mucosal mesalazine concentration, expressed as ng/mg of tissue, was significantly lower in patients with recurrence than in those without recurrence both in the ileum (mean +/- s.d.: 21.6+/-28.3 vs. 70.9+/-47.4; P = 0.007) and in the colon (25.8+/-26.4 vs. 60.3+/-32.5; P = 0.010). CONCLUSIONS: The mucosal concentration of mesalazine in the juxta-anastomatic area is significantly lower in patients with recurrence than in those free of recurrence. These data could suggest an association between mucosal mesalazine concentrations and the clinical effectiveness of the drug.

Adult↗
PubMed1999

Intestinal permeability test as a predictor of clinical course in Crohn's disease.

OBJECTIVE: The clinical course of Crohn's disease is often unpredictable. The aim of this study was to select the most useful parameters able to predict clinical relapses. METHODS: One hundred-thirty Crohn's disease patients in clinical remission were followed every 4 months for 2 yr or until clinical relapse. Demographic and clinical data were recorded and intestinal permeability (lactulose/mannitol [L/M] test) and biochemical tests (white blood cell count, erythrocyte sedimentation rate, C-reactive protein, alpha1 acid glycoprotein, and serum iron) were performed at study entry. A subgroup of 54 patients had clinical follow-up and repeated tests every 4 months. RESULTS: Fifty-two patients (40%) relapsed during the 2-yr follow-up. A significant correlation was found between relapse and gender (p = 0.030) but not between relapse and age, extent and type of disease, previous surgery, or therapy. Increased L/M test (p = 0.0001) and decreased serum iron level (p = 0.0057) were associated with clinical relapse. Time-dependent analysis, performed on patients receiving serial evaluation, showed that L/M test alteration was the only variable that could predict a relapse (RR 8.84, 95% confidence interval [CI] 1.41-53.37; p < 0.05). CONCLUSIONS: The L/M test identifies Crohn's disease patients in apparent remission, but with a high risk of clinical relapse, better than clinical and biochemical indices. Different treatment strategies might be suggested for this subgroup of patients.

Adolescent↗
PubMed1999

Zinc therapy increases duodenal concentrations of metallothionein and iron in Wilson's disease patients.

OBJECTIVE: Wilson's disease is effectively treated by zinc administration which, in vitro, increases metallothionein concentrations. To ascertain whether the latter also occurs in humans we measured metallothionein and trace element concentrations in the duodenal mucosa of 15 Wilson's disease patients: 12 treated with zinc sulphate, two treated with penicillamine, and one not yet on treatment. The control group consisted of 17 patients with dyspepsia, who underwent the same study protocol. METHODS: Metallothionein and trace element concentrations were measured in duodenal mucosa biopsies according to the silver-saturation hemolysate method and atomic absorption spectrophotometry. RESULTS: Metallothionein concentrations increased by 1500% after zinc and 150% after penicillamine in Wilson's disease patients, with respect to controls who had negative endoscopy and Wilson's disease patients who were not treated. A significant correlation was found between metallothionein and duodenal zinc concentrations. Mucosal iron concentration increased in Wilson's disease patients whether they were treated with zinc or penicillamine. Duodenum with duodenitis also had significantly increased iron levels compared with normal duodenum. CONCLUSIONS: Zinc administration increases intestinal metallothionein in Wilson's disease patients. The blockade of copper absorption and its elimination in the stools on desquamation of the intestinal cells probably explains one of the mechanisms underlying the effect of zinc treatment. Despite normal endoscopy, Wilson's disease patients present increased mucosal iron concentrations similar to those in controls with duodenitis. Metallothionein may therefore prevent oxidative damage caused by metal toxicity.

Adult↗
PubMed1999

Effect of moderate exercise on Crohn's disease patients in remission.

BACKGROUND: Physical exercise may exacerbate the disturbed homeostasis of Crohn's disease patients. AIM: To examine the effect of moderate physical exercise on gastrointestinal function in a group of Crohn's disease patients in remission. PATIENTS AND METHODS: The effect of one-hour's exercise at a maximum of 60% oxygen consumption was evaluated in six males with ileal Crohn's disease in remission on orocaecal transit time (breath test to lactulose), intestinal permeability (6-hours' urinary excretion of a sugar mixture of lactulose/mannitol), polymorphonuclear leucocytes function (peripheral blood chemiluminescence), lipoperoxidation (plasma malondialdehyde) and antioxidant trace elements (urinary and plasma zinc and copper concentrations). Six healthy age-matched subjects served as controls. RESULTS: Exercise did not elicit subjective symptoms or changes in intestinal permeability and lipoperoxidation. Orocaecal transit time increased after exercise in Crohn's disease patients (72 min +/- 30 vs 100 min +/- 34) with no significant difference from controls (77 min +/- 20 vs 83 min +/- 23). Neutrophils, primed pre-exercise in Crohn's disease patients showed an increased post-exercise chemiluminescence similar to controls. Zinc urinary output significantly increased after exercise in Crohn's disease patients and remained unchanged in control subjects. CONCLUSIONS: Moderate aerobic exercise has no significant effect on the gastrointestinal parameters examined. However, basal neutrophil activation and exercise in Crohn's disease patients may trigger an excessive production of oxygen metabolites. Moreover, exercise may contribute to an increased risk of zinc deficiency.

Adolescent↗
PubMed1999

Mutation analysis in patients of Mediterranean descent with Wilson disease: identification of 19 novel mutations.

In this study, we report further results of mutation analysis of the ATP7B gene in Wilson disease (WD) patients of Mediterranean origin. A total of 136 WD chromosomes, 73 of which were of Italian, 43 of Turkish, 18 of Sardinian, and two of Spanish origin, were analysed and the mutation characterised in 84.5% of them. We found 50 different mutations of which 19 are novel, including three nonsense, one frameshift, and 15 missense mutations. The mutations detected were rare and mostly found in the compound heterozygous state together with other mutations and only rarely in homozygosity. Most of these mutations lie in the transmembrane and ATP binding loop regions. These data expand our knowledge of both the structure-function relationships of the WD protein and the molecular pathology of WD, thus improving our capability of prevention and genetic counselling.

Adenosine Triphosphatases↗
PubMed1999

Mesalazine foam (Salofalk foam) in the treatment of active distal ulcerative colitis. A comparative trial vs Salofalk enema. The SAF-3 study group.

BACKGROUND: Mesalazine enemas are of well proven efficacy for the topical treatment of distal ulcerative colitis. Although new rectal formulations of mesalazine are not expected to be superior in efficacy and tolerability to standard formulations, they may offer secondary advantages in terms of overall acceptability. AIM: To compare the efficacy, tolerability and overall acceptability of a new mesalazine rectal foam (Salofalk foam) with mesalazine enema in the treatment of active distal ulcerative colitis. PATIENTS AND METHODS: A multicentre study was carried out in patients with active proctitis, proctosigmoiditis and left-sided ulcerative colitis as evaluated by the Clinical Activity Index (CAI > or =4) and Endoscopic Index (EI > or =6). Patients were randomly assigned to receive, in open-label fashion, either mesalazine foam 2 g twice a day or mesalazine enema (2 g/60 ml twice a day) for 3 weeks. Patients who did not achieve remission (defined as CAI <4 and EI <6) after 3 weeks continued the study receiving the alternative galenic formulation for a further 3 weeks. RESULTS: A total of 195 patients were enrolled. Characteristics at baseline were similar except for concomitant therapy with oral 5-ASA products: during the 1st treatment phase, 41% of patients on enema received such treatment vs only 29% of those on foam. Patients with at least one post-treatment efficacy evaluation were included in the intent-to-treat analysis (n=89 foam, n=96 enema). After 3 weeks of treatment, 112 patients were in remission and only 59 patients entered the 2nd treatment phase thus providing data on acceptability. Remission was achieved after 3 weeks in 54% of patients treated with foam and in 67% of those treated with enema. The 90% confidence interval for the difference in remission rates was 0 to 24 and thus within the clinically acceptable range of therapeutic equivalence. At the end of the 2nd phase, 70% of patients switched to foam were in remission vs 65% to the enema. Two patients discontinued treatment with foam prematurely due to anal burning. No clinically important changes were seen in the laboratory tests. CONCLUSIONS: Salofalk foam and enema are equally effective for the treatment of proctitis, proctosigmoiditis and left-sided ulcerative colitis. The new foam preparation is as well tolerated and accepted as enemas and can be used as a therapeutic alternative to conventional mesalazine enema formulations.

Administration, Topical↗
PubMed1999

Experimental colitis increases small intestine permeability in the rat.

Small intestine permeability is frequently altered in patients with Crohn's disease and is thought to play a pathogenic role. The aim of this study was to investigate the permeability and structure of small intestine tight junctions (TJ) in an animal model of chronic distal colitis. Seven days after colitis induction with trinitrobenzenesulfonic acid/ethanol, the duodenal and ileal TJ were studied by means of transmission electron microscopy using lanthanum nitrate, freeze fractures, and immunohistochemistry of occludin, ZO-1, and cingulin. Animals treated with intrarectal ethanol alone served as controls. In controls, 7.5% of duodenal and 9.6% of ileal TJ were permeable to lanthanum, whereas in colitis, permeability increased significantly (79.5% and 72.9%, respectively; p < 0.001, both segments compared with controls). In colitis, the percentage of "leaky" junctions in duodena as well as in terminal ilea correlated positively with the macroscopic colon damage score (p < 0.02 and p < 0.005, respectively). Freeze-fracture analysis and immunohistochemistry of cingulin and ZO-1 did not reveal any difference between control and treated animals, whereas the signal of the transmembrane protein occludin was found to be disrupted and irregular in both small intestine segments. Distal colitis induces an increase of TJ permeability throughout the entire small intestine, and the extent of alterations correlates with colonic damage. Alterations in the transmembrane protein occludin seem to be responsible for the observed changes. Further investigation is needed to elucidate the mechanism of TJ alterations by a remote focus of inflammation.

Animals↗
PubMed1998

Further delineation of the molecular pathology of Wilson disease in the Mediterranean population.

This study presents the update results of an ongoing project on the delineation of the spectrum of mutations at the Wilson disease (WD) gene in WD patients of Mediterranean origin. In studying 59 patients, of whom were 26 Continental Italians, 22 Sardinians, 9 Turkish, and 2 Albanians, we have found 31 novel and three known mutations. Of the novel mutations, 3 are deletions, two nonsense, 2 splice or consensus splice site, and 24 missense. The large majority of the missense mutations lie in evolutionary conserved regions of the WD gene of documented functional importance. Most of our patients were compound heterozygotes, and only a few were homozygotes. In addition, three polymorphisms were detected. By adding the new data to those previously reported by our group, we have to date detected 85% of mutations in the WD chromosomes from Continental Italians, 30% from Sardinians, 81.7% from Turkish and 66.7% from Albanians. Most of the mutations characterized are rare, and only a limited number are common. Of the common mutations 5 were found in Continental Italians, two in Sardinians and a single one in Turkish. Because there are so many causative mutations of the disease, the preclinical and prenatal diagnosis of WD should be carried out by a combination of mutation and linkage analysis.

Adenosine Triphosphatases↗
PubMed1998

The effect of heparin on trinitrobenzene sulphonic acid-induced colitis in the rat.

BACKGROUND: Reduced blood coagulability seems to protect against inflammatory bowel disease; pilot studies using heparin in patients with inflammatory bowel disease have reported positive results. AIM: To evaluate the effects of heparin treatment on microangiographic and on inflammatory parameters in experimental colitis, induced by trinitrobenzene sulphonic acid (TNBS)-ethanol. METHODS: Four groups of rats: (i) controls (saline enema), TNBS-induced colitis with (ii) sham treatment (saline, s.c.), (iii) dexamethasone (0.25 mg/kg/day s.c.) and (iv) heparin (500 U/kg t.d.s., s.c.). Microangiography was performed 2 and 4 days after colitis induction. Partial thromboplastin time, colonic wet weight, macroscopic damage score and mucosal myeloperoxidase (MPO) activity were determined at day 4. RESULTS: TNBS-induced colitis caused a reduction in visible bowel wall vessels, which was prevented by heparin (P < 0.05) but not by steroids. The macroscopic damage scores and colon wet weights were similar in all colitis groups. Compared to untreated colitis the MPO activity in heparin-treated animals was of borderline significance. CONCLUSIONS: Heparin treatment improved microangiographic features and reduced inflammation to a certain degree. Steroids delayed development of colon hypoperfusion, but were ineffective on MPO activity. It remains to be determined if the observed effects are due to the antithrombotic activity of heparin or to an anti-inflammatory action.

Animals↗
PubMed1998

Hepatobiliary alterations in patients with inflammatory bowel disease: a multicenter study. Caprilli & Gruppo Italiano Studio Colon-Retto.

BACKGROUND AND METHODS: Four hundred and eighty-four patients with inflammatory bowel disease underwent clinical examination, ultrasonography, and biochemical liver function tests, to estimate the prevalence of hepatobiliary alterations. The patient group included patients without a history of liver disease. Controls were recruited from patients with functional symptoms. RESULTS: More patients with ulcerative colitis than controls had liver steatosis and increased alkaline phosphatase levels. Factors increasing the probability of liver damage were long-standing disease, the presence of moderate/severe disease activity, and treatment with steroids and mesalazine. A significant association was found between biliary disease and long-standing colitis and also therapy with steroids and mesalazine. Alkaline phosphatase and aminotransferase levels were significantly higher in Crohn's disease patients than in controls. Hepatic and biliary damage was found more commonly in the 1st year after diagnosis. CONCLUSIONS: The monitoring of hepatobiliary function is suggested for patients with inflammatory bowel disease, even in the absence of symptoms and history.

Adolescent↗
PubMed1998

Altered plasma and mucosal concentrations of trace elements and antioxidants in active ulcerative colitis.

BACKGROUND: The production of free radicals is increased in inflammatory bowel disease, and trace elements are crucial components of several antioxidants. Trace elements deficiency may therefore compromise the defense against oxidative damage. The aims of this study were to measure plasma and tissue concentration of trace elements and antioxidants and to relate this to disease activity. METHODS: A 10-ml blood sample and six colonic biopsy specimens were obtained from 24 patients with either active ulcerative colitis or in remission and 10 patients with irritable bowel syndrome for measurement of trace elements and trace element-dependent enzymes. RESULTS: Patients with moderately active disease had significantly lower plasma iron, selenium, and glutathione peroxidase levels than patients in remission and controls, whereas no significant differences were found between the zinc and copper values of patients and controls. Mucosal concentrations of zinc and metallothionein were reduced, whereas iron and glutathione peroxidase concentrations were increased in patients with endoscopically active disease as compared with controls and patients in remission. CONCLUSIONS: Patients with ulcerative colitis have altered plasma and tissue levels of trace elements and antioxidant-related enzymes. The resulting reduced protection against free radicals may contribute to the inflammatory process.

Adult↗
PubMed1998

Maintenance treatment of ulcerative proctitis with mesalazine suppositories: a double-blind placebo-controlled trial. The Italian IBD Study Group.

OBJECTIVES: A multicenter double-blind placebo-controlled clinical study was conducted to evaluate the efficacy and tolerability of two different therapeutic schedules of mesalazine suppositories in patients with ulcerative proctitis. METHODS: From 1990 to 1993, 111 patients with ulcerative proctisis in remission, limited to the rectum (< or = 15 cm from anus), were enrolled. After obtaining informed consent, patients were randomized to three treatment groups: 500 mg mesalazine b.i.d. (36 patients), 500 mg mesalazine u.i.d. (40 patients), and placebo (35 patients). The treatment lasted 1 yr. Follow-up consisted of periodic clinical, endoscopic, and histological assessments. An endoscopic score > 1 according to the Baron scale defined relapse occurrence. The three groups were homogeneous as regards main demographic, diagnostic, and prognostic features. RESULTS: The cumulative relapse rates at 12 months were 10% (95% confidence interval [CI]: 0-21) in the mesalazine b.i.d. group, 32% (95% CI: 16-49) in the mesalazine u.i.d. group, and 47% (95% CI: 29-65) in the placebo group. The comparison between the mesalazine b.i.d. group and the mesalazine u.i.d. group cumulative relapse rates gave a p value of 0.0334, whereas the corresponding comparison between the mesalazine b.i.d. group and the placebo group gave a p value of 0.007 (log-rank test). The dose-response relationship was statistically significant (p = 0.008 by Cox analysis). Two patients in the mesalazine b.i.d. group, two patients in the mesalazine u.i.d. group, and one patient in the placebo group withdrew from the study due to nonserious adverse events; four, three, and four patients per group, respectively, dropped out because of poor compliance. Two patients in the mesalazine u.i.d. group and two in the placebo group were lost to follow-up. CONCLUSIONS: The results of this study confirm the therapeutic efficacy of mesalazine suppositories in the maintenance treatment of ulcerative proctitis. According to our experience the most effective therapeutic schedule is 500 mg mesalazine b.i.d.

Adolescent↗
PubMed1997

Quinone-induced DNA single strand breaks in a human colon carcinoma cell line.

It has been demonstrated that synthetic quinones, such as menadione, cause DNA damage in different cell systems, possibly being mediated by free radicals generated during redox cycling. It has been suggested that the damage caused could be related to tumor induction in different sites. To our knowledge it has not yet been demonstrated that the natural quinones, vitamin K1 and K2, exert the same activity. Using a colon carcinoma cell line, HT-29, we examined the extent of DNA damage induced by menadione, vitamin K1 and K2. Menadione caused significant DNA damage at low concentrations (25-200 microM) with a linear correlation of r = 0.95. In the presence of dicoumarol, a DT-diaphorase inhibitor, the damage was detected at concentrations five times lower indicating that free radicals generated during the redox cycling play a key role. Neither vitamin K1, incorporated in micelles, nor K2 caused detectable single strand breaks with respect to the controls either in the presence or in absence of dicoumarol. Our results demonstrate that, despite their redox cycling properties, the natural forms of vitamin K do not cause DNA damage in HT-29 cells as menadione does in the experimental conditions used.

DNA↗
PubMed1996

Effect of zinc supplementation on metallothionein, copper, and zinc concentration in various tissues of copper-loaded rats.

The present study was designed to investigate the effects of Zn administration on metallothionein concentrations in the liver, kidney, and intestine of copper-loaded rats. Male CD rats were fed a diet containing 12 mg Cu and 67 mg Zn/kg body wt. They were divided into either acute or chronic experimental protocols. Rats undergoing acute experiments received daily ip injections of either Cu (3 mg/kg body wt) or Zn (10 mg/kg body wt) for 3 d. Chronic experiments were carried out on rats receiving Cu ip injections on d 1, 2, 3, 10, 17, and 24, Cu injections plus a Zn-supplemented diet containing 5 g Zn/kg solid diet, or a Zn-supplemented diet alone. Rats injected Zn or Cu had increased MT concentrations in liver and kidney. Zn produced the most important effects and the liver was the most responsive organ. Rats fed a Zn-supplemented diet had significantly higher MT concentrations in liver and intestine with respect to controls. Increased MT synthesis in the liver may contribute to copper detoxification; the hypothesis of copper entrapment in enterocytes cannot be confirmed.

Animals↗
PubMed1996

Immunohistochemical expression of metallothionein in normal human colorectal mucosa, in adenomas and in adenocarcinomas and their associated metastases.

The immunohistochemical distribution pattern of metallothionein, a low molecular weight protein with strong affinity for divalent heavy metal ions, has been investigated in normal and neoplastic conditions of the large bowel. Utilizing a monoclonal mouse antibody the following formalin-fixed paraffin-embedded surgical or biopsy samples were studied: tubulo-villous adenomas (8 cases); adenocarcinomas with various degree of differentiation (85), nine of which were mucinous-type; synchronous tubular or tubulo-villous adenomas separate from carcinomas (30); transitional mucosa (45); metastases in lymph nodes (43); and distant metastases (45). Twenty biopsies from the right and left colon of 10 patients affected by irritable bowel syndrome were also analyzed. Normal colonic mucosa as well as transitional mucosa showed metallothionein immunopositivity in enterocytes at the luminal surface and crypts. Evident nuclear and cytoplasmic staining was encountered in tubulo-villous adenomas; the same reactivity was noted in the basal glandular component of colorectal carcinomas-synchronous adenomas, while less intense staining was noted in the apical villous portions. A variable metallothionein immunostaining was observed in adenocarcinomas (62.3%), in lymph node (55.8%) and distant hepatic (17.2%) and omental (43.8%) metastases, although it was not always concordant with that reported in the corresponding primary tumour. Whether the metallothionein positivity observed in normal and neoplastic cells is the result of expression of a stable form of the protein or an accumulation in the nucleus and cytoplasm remains to be clarified.

Adenocarcinoma↗
PubMed1995

Functional and morphological changes in small bowel of Crohn's disease patients. Influence of site of disease.

Morphological and functional changes were examined in the upper jejunum and terminal ileum of 18 patients suffering from Crohn's disease. Intestinal permeability, biochemical determination of enzymatic activities, and morphologic evaluation of the severity of the lesions were evaluated. Ulcerative colitis and irritable bowel syndrome patients served as controls. We found abnormal lactulose-mannitol tests in all patients with active Crohn's disease. Permeability changes correlated with increased crypt cell proliferation, as indicated by thymidine kinase activity. A significant reduction in brush border enzyme activities was seen in the terminal ileum, but no significant change was observed in the unaffected upper jejunum. The number of mast cells was increased in the diseased ileum. We conclude that the site of inflammation and the healing capacity of the epithelium are important in determining functional and biochemical abnormalities in active Crohn's disease. Changes may be dependent on the type and number of immune cells involved in the inflammatory process.

Adult↗