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R Naccarato

Publications and source records attributed to R Naccarato.

At least 55 records · Page 3Linked to original sources
PubMed1997

Urokinase-type plasminogen activator receptor in gastric cancer: tissue expression and prognostic role.

The urokinase-type plasminogen activator (UPA) and its inhibitor PAI-1 are thought to play an important part in gastric cancer (GC) invasion and metastasis. Little is known about the behavior and prognostic impact of the receptor for UPA (UPAR). The aims of the present study were: (1) to measure UPAR, UPA and PAI-1 levels in GC and in non-malignant tissue distant from the tumor (NORM); (2) to evaluate their relationship with histomorphological parameters; and (3) to determine their prognostic value. UPAR, UPA and PAI-1 levels were determined by ELISA in GC and NORM samples from 20 patients with GC undergoing surgery. The GC was also examined in terms of the presence (n = 10) or absence (n = 10) of metastasis, differentiation (five differentiated, 15 undifferentiated) and histotype. Survival was analysed using life table analysis. UPAR, UPA and PAI-1 were significantly higher in GC vs NORM, in the presence of metastasis (UPAR, UPA) and in undifferentiated GC (UPAR, PAI-1). UPAR significantly correlated with UPA and PAI-1. Low levels of UPAR (P = 0.04), UPA (P = 0.007) and PAI-1 (P = 0.02) were associated with a better survival. Our results demonstrate a sharp increase in UPAR in GC and suggest a prognostic role for it. The concomitant activation of UPAR, UPA and PAI-1 in GC confirm the important role of the plasminogen activator system in the process of invasion and metastasis.

Adult↗
PubMed1997

Effects of cyclosporin A on paracellular and transcellular transport of horseradish peroxidase in perfused rat livers.

The immunosuppressive agent cyclosporin A (CsA) is known to cause cholestasis. Transcellular and paracellular transport of macromolecules contribute, albeit to a minor extent, to bile formation, but little is known about the effects of CsA on these pathways. The aims of this study were to investigate the influence of CsA on tight junction (paracellular) permeability and on transcytotic vesicular pathways labeled with horseradish peroxidase (HRP) in perfused rat liver. Livers from male Sprague-Dawley rats were perfused with Krebs-Henseleit buffer (albumin 1%, RBC 20%, and amino acid mixture). Taurodehydrocholate (1 microM/min) was coinfused into the portal vein; 1 microg/ml of CsA, dissolved in Cremophor-EL (CsA livers), or the vehicle alone (CEL livers), was added to the medium. Tight junction permeability was assessed by administering HRP (25 mg) as a short pulse to perfused rat livers, operating under single-pass conditions. Under such conditions, HRP output into the bile shows two components: an initial peak at approximately 3-5 min, corresponding to paracellular transfer across tight junctions, and a second peak at approximately 15 min, corresponding to vesicular transport. Furthermore, we assessed the vesicular transport pathway by examining HRP-labeled vesicles in the perisinusoidal (PS) and pericanalicular (PC) areas using ultrastructural morphometric analysis. To analyze HRP in hepatocytes and to study rapid and late transcytotic vesicular pathways, a 1-min pulse of a high dose of HRP (500 and 200 mg, respectively) was given. Two and 18 min after single-pass perfusion the livers were fixed with 2.5% glutaraldehyde-0.8% paraformaldehyde in 0.1 mM cacodylate buffer, pH 7.8. The total pericanalicular area, the HRP-containing structures, were quantified morphometrically in liver samples. At concentrations of 1.2 microg/ml, CsA produced a twofold increase in the paracellular transfer of HRP to bile. The areas under the second peak (transcellular vesicular pathway) of the biliary HRP secretion curve were similar in CEL- and CsA-treated livers. Morphometric analysis confirmed that CsA treatment did not affect the percentage area of HRP-labeled vesicles in either the pericanalicular or in the perisinusoidal area at 2 min (rapid pathway) and 18 min (late pathway). These results indicate that CsA increases tight junctional permeability whereas it does not inhibit rapid or late transcytotic vesicle pathways.

Animals↗
PubMed1997

Hepatocyte tight-junctional permeability is increased in rat experimental colitis.

BACKGROUND & AIMS: Hepatobiliary complications occur in inflammatory bowel disease and may be caused by the translocation of intestinal toxins from portal blood into bile through leaky hepatocyte tight junctions. The role of tight junctions in the pathogenesis of hepatobiliary complications in experimental inflammatory bowel disease was investigated. METHODS: Colitis was induced in rats by intracolonic instillation of trinitrobenzene sulfonic acid. The function of hepatocellular tight junctions was evaluated in perfused livers by measuring early (paracellular) horseradish peroxidase excretion into the bile and by electron microscopy and semiquantitative analysis of lanthanum penetration through the tight junction and into bile canaliculi. Immunofluorescent localization of cingulin and ZO-1 was used to study the structure of hepatocyte junctions. RESULTS: Colitis was associated with increased serum bilirubin and bile acid concentrations, a 2.5-fold increase in paracellular biliary excretion of horseradish peroxidase, and a ninefold increase in lanthanum permeability. Liver histology and cingulin and ZO-1 localizations were similar to normal liver. CONCLUSIONS: Experimental colitis is associated with hepatobiliary complications and an increased hepatocyte tight junctional permeability to horseradish peroxidase and lanthanum. Subtle alterations in tight junction function may be involved in the pathogenesis of hepatobiliary injuries in inflammatory bowel disease.

Animals↗
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↗
PubMed1997

A 3-year pilot study with 1,25-dihydroxyvitamin D, calcium, and calcitonin for severe osteodystrophy in primary biliary cirrhosis.

We carried out a 3-year pilot study of 59 consecutive women with osteoporosis of primary biliary cirrhosis (PBC), allocating them to two groups according to the severity of bone demineralization assessed by means of dual-photon absorptiometry (DPA) of the lumbar spine, Group A (36 patients; bone mineral density [BMD] > 0.800 g/cm2) received no treatment; group B (23 patients; BMD < 0.800 g/cm2) was treated as follows: oral 1,25-dihydroxyvitamin D (0.5 microgram twice a day for 5 days) followed by a 1-month course with oral calcium carbonate (1,500 mg/day) +carbocalcitonin (40 UMRC intramuscularly three times weekly). This treatment was repeated every 3 months. The following parameters were assessed at baseline and every 12 months: DPA, serum and urinary minerals, serum parathyroid hormone (PTH), osteocalcin (BGP), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D. During follow-up, 11 initially untreated patients whose BMD dropped below 0.800 g/cm2 were switched to the treatment group (8 after 12 months and 3 after 24 months). No significant changes were observed in either group for PTH, BGP, or vitamin D metabolites. Comparing patients who were always treated, those who were never treated, and those who switched to the treatment group (ever treated) in this 36-month period, the percentage of annual bone loss in the never-treated patients was significantly less (p < 0.002) than in the ever-treated patients, suggesting the presence of two subgroups in PBC patients; one with rapid bone loss and the other with slow bone loss. Moreover, in the ever-treated patients, ADFR (activate, depress, free, repeat) therapy resulted in an improvement in BMD (p < 0.05 compared with the value before therapy). We conclude that ADFR therapy is effective in the treatment of patients with PBC with severe osteodystrophy, despite no change in osteoblastic activity, although controlled, randomized studies are in order to confirm our data.

Bone Density↗
PubMed1997

Impaired fibrinolysis and increased protease levels in gastric and duodenal mucosa of patients with active duodenal ulcer.

OBJECTIVES: Cathepsin B and L (cysteine proteases), urokinase- and tissue-type plasminogen activators (serine proteases), and type-1 inhibitor are involved in gastric mucosal injury. We determined tissue protease levels in duodenal ulcer and their relationship to ulcer phase, bleeding tendency, Helicobacter pylori infection, and use of H2-blockers. METHODS: Endoscopic biopsies of antral and duodenal mucosa were obtained from 61 patients with active or healed duodenal ulcer and control subjects. Antigen concentrations were measured by ELISA. RESULTS: Significantly higher levels of cathepsins, urokinase-type plasminogen activator, type-1 inhibitor, and significantly lower levels of tissue-type plasminogen activator were found in active ulcers. Bleeders had the highest cathepsins and urokinase-type plasminogen activator levels. Higher levels of urokinase-type plasminogen activator, cathepsin B, and type-1 inhibitor were observed in Helicobacter pylori-positive patients. CONCLUSIONS: Our results suggest that impaired fibrinolysis (tissue-type plasminogen activator), intramucosal proteases (cathepsins), tissue remodeling, and angiogenesis (urokinase-type plasminogen activator and type-1 inhibitor) are involved in duodenal ulcer formation and healing.

Adult↗
PubMed1997

Chronic atrophic gastritis and Helicobacter pylori infection in primary biliary cirrhosis: a cross-sectional study with matching.

BACKGROUND/AIMS: Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by exocrine gland impairment. Up to now there have been no reports dealing with gastric mucosa involvement in this autoimmune condition, which is frequently associated with Sjögren's syndrome. The aim of this study was to investigate the morphologic, biochemical and immunological features of the gastric mucosa in PBC. METHODS: A cross-sectional study with matching was performed. Thirty-three PBC patients (30 F, 3 M, mean age 58 years; 17 with stage II-III, and 16 with stage IV disease) and 33 sex- and age-matched dyspeptic controls were included. Six biopsy specimens from the fundus (2), body (2) and antrum (2) were taken from all patients and controls. A serological assessment was performed for each subject, i.e. pepsinogen A (PGA), pepsinogen C (PGC), gastrin (G), and antibodies against Helicobacter pylori (anti-Hp IgG). RESULTS: Endoscopic gastritis was found in 22 PBC patients (66.6%). There was no difference between PBC patients and controls regarding the percentage of subjects with mild, moderate, severe or atrophic gastritis (AG). There was no difference in gastric mucosal involvement between PBC subjects with or without secondary Sjögren's syndrome. A discrepancy was observed in the data obtained with respect to Helicobacter pylori (H. pylori) infection. H. pylori colonization was significantly more frequent in controls than in PBC patients (79% vs 49%, p < 0.002), but anti-Hp IgG were detected in the same percentage in the two groups (90% vs 83% respectively). There was no difference between the two groups in the PGA, PGC, PGA/PGC ratio, or gastrin. Eight PBC patients had esophageal varices. CONCLUSIONS: PBC patients are not characterized by chronic atrophic gastritis. Even though they present chronic gastritis with the same prevalence as dyspeptic controls, and show signs of previous H. pylori infection as frequently as dyspeptic patients, they are actually much less frequently infected. The reasons for this observation are unclear.

Adult↗
PubMed1997

Fasting hyperglycaemia following trans-catheter arterial chemo-embolization for hepatocellular carcinoma in cirrhosis.

BACKGROUND AND AIMS: Following a hyperosmolar diabetic coma in a cirrhotic patient with hepatocellular carcinoma undergoing transcatheter arterial chemo-embolization, we assessed the prevalence, severity, causes and prognostic impact of impaired glucose metabolism following transcatheter arterial chemo-embolization. METHODS: Plasma glucose, pancreatic and thyroid hormones, cortisol, growth hormone, ACTH and TSH concentrations were determined before and after transcatheter arterial chemo-embolization in 98 patients (70 with a normal fasting glucose, 7 with mild fasting hyperglycaemia and 21 diabetics) undergoing 226 transcatheter arterial chemo-embolization procedures. Child status, body temperature, serum ALT and amylase levels, tumour size, gelfoam embolization and disease aetiology were recorded. Liver function was assessed before and after transcatheter arterial chemo-embolization by measuring monoethylglycinexylidide formation after i.v. lidocaine. RESULTS: A significant rise in glucose levels (p < 0.0001) was observed in 30/98 patients. Hyperglycaemia was more frequent in diabetics (67%) and patients with mild fasting hyperglycaemia (71%). Glucose concentrations doubled in 12 patients; 4 required long-term insulin. Fever, a previously altered carbohydrate metabolism and raised ALT levels were prognostic factors for hyperglycaemia (p < 0.01). Plasma C-peptide, glucose/insulin and glucose/C-peptide ratios, were increased after transcatheter arterial chemo-embolization (p < 0.05). Transcatheter arterial chemo-embolization was followed by a reduction in the monoethylglycinexylidide formation capacity (p < 0.05), particularly in hyperglycaemia patients (p < 0.02). CONCLUSIONS: Transcatheter arterial chemo-embolization is frequently followed by a derangement in glucose metabolism which is potentially severe, associated with preceding glucose imbalance, fever and a transient deterioration in liver function.

Adult↗
PubMed1996

[Prognostic role of cisteine and serin proteases in gastriC cancer].

Cysteine proteases (cathepsin B and L), the serine protease urokinase-type plasminogen activator and its inhibitor type-1 play an important part in cancer invasion and metastasis. The authors determined the protease concentrations in gastric cancer tissues, using the ELISA method, in patients with gastric cancer. They evaluated the prognostic role of proteases and the relationship that these proteases may have with other histomorphological prognostic parameters such as tumor staging, grading, histotype, Borrmann classification. The Cox survival analysis showed that cathepsin B (p = 0.002), urokinase-type plasminogen activator (p = 0.0001) and the inhibitor type-1 (p = 0.0004) significantly correlated with poor prognosis. The tumor staging, grading, Borrmann classification correlated also significantly with survival time. Urokinase-type plasminogen activator was selected as the single independent variable in the Cox model (p = 0.0001).

Adult↗
PubMed1996

Unresectable hepatocellular carcinoma in cirrhosis: survival, prognostic factors, and unexpected side effects after transcatheter arterial chemoembolization.

To evaluate the efficacy of transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma, the prognostic factors, and the side effects, 72 patients undergoing 170 chemoembolizations with lipiodol-mediated injection of adriamycin were investigated. The 1-, 2-, and 3-year survivals are 83, 61, and 56%, respectively. Significant prognostic factors for survival (by Mantael-Haenszel) are Child-Pugh and Okuda status (p = 0.00001 and p = 0.01 respectively), number of TACE courses (p = 0.002) and of courses completed with embolization (p = 0.05), stabilization or reduction of alpha-fetoprotein (p = 0.003), and concurrent tamoxifen treatment (p = 0.04). Side effects included fever, pain, increased serum amylase and transaminase levels, and one liver abscess with death of liver failure. In addition, mild hyperglycemia was observed in 19% of patients and severe in 8% (with one hyperosmolar diabetic coma), in the absence of pancreatic damage. In conclusion, transcatheter arterial chemoembolization is useful in patients with unresectable hepatocellular carcinoma. Prognostic factors are Child-Pugh and Okuda status, number of TACE courses and of embolizations, changes of alpha-fetoprotein levels, and association with tamoxifen treatment. The development of mild to severe changes of glucose metabolism suggests that glucose tolerance should be evaluated before and glycemia strictly monitored after each TACE course.

Abdominal Pain↗
PubMed1996

Two different dosages of yeast derived recombinant hepatitis B vaccines: a comparison of immunogenicity.

The efficacy of a 10 or 20 micrograms antigen load of HB recombinant vaccines is still being debated. A comparison of anti-HBs titres in two groups of healthy subjects vaccinated by the same schedule (0, 1 and 6 months) employing recombinant HB vaccines with different antigen loads, 20 micrograms (group A, 251 subjects) and 10 micrograms (group B, 256 subjects) was carried out. A seroprotection rate of 99.6 and 99.2% was observed for group A and group B, respectively, at the end of primary immunization. No statistically significant difference in seroprotection rate was observed. Group A showed significantly higher GMTs than group B for all age groups and for both sexes except for males above 25 years. The difference was more marked for younger age groups and for the female sex. These data support the higher immunogenicity of vaccine with 20 micrograms antigen load as compared to vaccines with 10 micrograms antigen load.

Adolescent↗
PubMed1996

Risk factors in community-acquired chronic hepatitis C virus infection: a case-control study in Italy.

AIMS/METHODS: A case-control study was carried out in Italy to assess the risk factors associated with chronic hepatitis C virus infection. Five hundred consecutive chronic anti-hepatitis C virus positive cases and 500 sex and exactly age-matched anti-hepatitis C virus negative/HBsAg negative controls entered the study. Information was collected through an interviewer-administered questionnaire. The adjusted Odds Ratios linking hepatitis C virus infection and risk factors were estimated by conditional multiple logistic regression. Demographic and socio-economic characteristics were similar in cases and controls. Seventy-five percent of patients were aged over 40: males were prominent in the group < or = 40, while the number of females increased with age. RESULTS: As expected, drug addiction and blood transfusion emerged as independent risk factors: blood transfusion in all ages and in both sexes, drug addiction only in subjects under 41 years and mostly in males. Other risk factors independently associated with hepatitis C virus infection were: previous use of non-disposable needles, previous tuberculosis, and prolonged hospitalization before 1970. A history of sexually-transmitted diseases was not associated. CONCLUSIONS: This study shows that the great spread of hepatitis C virus in Italy may have occurred several years ago through parenteral routes which are not now operating. Modern hygienic and sanitation measures have significantly controlled exposure to the infection, which in the younger generations is confined to high-risk groups such as drug addicts.

Adult↗
PubMed1996

Hepatocyte proliferative activity in chronic liver damage as assessed by the monoclonal antibody MIB1 Ki67 in archival material: the role of etiology, disease activity, iron, and lipid peroxidation.

Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related liver damage is linked to an increased risk of hepatocellular carcinoma, but the mechanisms underlying hepatitis C viral activity are not known. We therefore compared hepatocellular proliferative activity in chronic C virus-related hepatitis and in liver damage of other etiology. Hepatocyte proliferation rate was investigated in 56 patients with chronic hepatitis using the Ki67 MIB1 monoclonal antibody in archival material. According to etiology, the patients were subgrouped as follows: HCV (34), HBV (11), Alcohol (4), HCV + Alcohol (4), and Hemochromatosis (3). Proliferation rate was correlated with age, sex, etiology, disease activity, liver iron storage, free-radical production, and glutathione levels by regression and discriminant analysis. HCV-positive patients had significantly more MIB1-positive hepatocytes in the periportal area (P < .011) and in the low-proliferating perivenular area (zones 2 and 3) (P < .05). The number of MIB1-positive cells correlated directly with alanine transaminase (ALT) levels, Knodell index (KI), and, inversely, with iron saturation. By stepwise discriminant analysis, ALT levels and etiology were identified as single independent variables. These data suggest that HCV infection induces increased and abnormal hepatocyte proliferation, which might be related to the increased risk of hepatocellular carcinoma in patients with HCV-related liver damage.

Adult↗
PubMed1996

Increased levels of cathepsin B and L, urokinase-type plasminogen activator and its inhibitor type-1 as an early event in gastric carcinogenesis.

BACKGROUND: Cysteine proteases [cathepsin B (CATB), cathepsin L (CATL)], the serine protease urokinase-type plasminogen activator (UPA) and its inhibitor type-1 (PAI-1) play an important part in cancer invasion. No data are available on the relationship between these proteases and gastric precancerous changes. AIMS: To determine CATB, CATL, UPA, PAI-1 in chronic atrophic gastritis, intestinal metaplasia and gastric epithelial dysplasia, as precancerous changes, and to compare these data with those obtained in gastric cancer. PATIENTS: Endoscopic biopsies were obtained from 12 patients with gastric cancer (cancerous tissue), 33 patients with chronic atrophic gastritis (all with intestinal metaplasia and 12 with dysplasia) and from 47 control subjects, for a total of 92 patients. METHODS: Antigen concentrations were measured using ELISA methods. Immunohistochemistry was performed using monoclonal anti-CATB and anti-PAI-1 antibodies. RESULTS: CATB, CATL, UPA and PAI-1 were significantly higher in chronic atrophic gastritis than in controls (CATB: P < 0.001; CATL: P < 0.005; UPA: P < 0.000001; PAI-1: P < 0.005). The same was observed for cancer. CATB and UPA were significantly higher in chronic atrophic gastritis, with versus without dysplasia (P < 0.05). Dysplastic epithelia showed strong immunoreactivity to PAI-1 and CATB. CONCLUSIONS: Our study demonstrates that cathepsins, UPA and PAI-1 may have a role not only in the process of cancer invasion, but also in the progression of precancerous changes into cancer.

Adult↗
PubMed1996

Gastric antioxidant, nitrites, and mucosal lipoperoxidation in chronic gastritis and Helicobacter pylori infection.

We have evaluated gastric juice pH, nitrites and vitamin C levels, mucosal glutathione, and malondialdehyde, a marker of lipid peroxidation, in patients with chronic gastritis undergoing endoscopy. Patients had chronic gastritis with (n = 28) or without (n = 60) atrophy and/or concomitant Helicobacter pylori infection. Nineteen healthy subjects, without major macroscopic or histologic changes, were included as controls. Ten subjects were studied before and after H. pylori eradication. Vitamin C levels were low in atrophic gastritis (p < 0.006) and H. pylori infection (p < 0.02). Nitrite concentrations and pH were significantly higher in atrophy (p < 0.005 and 0.0001). Glutathione turnover was higher than normal in gastritis, with higher levels of oxidized glutathione (p < 0.02). Gastric malondialdehyde levels were significantly increased by gastritis (p < 0.05) and H. pylori infection (p < 0.05). Overall, more active gastritis coincided with lower vitamin C levels and higher malondialdehyde levels. After H. pylori eradication a drop in mucosal MDA levels was observed (p = 0.04). In summary, chronic gastritis and H. pylori infection correlate with increased free-radical production, reduced gastric vitamin C levels, and increased glutathione turnover. The possible implications of these changes in the pathogenesis of gastric damage and in carcinogenesis are intriguing.

Adult↗
PubMed1996

Changing approach to gastroenteropancreatic tumours. Case report of a gastrinoma metastasis localized by somatostatin-receptor scintigraphy.

A 60-year-old female with a history of chronic pancreatitis and previous pancreaticojejunostomy has been submitted to distal gastric resection for recurrent perforating ulcers. A carcinoid tumour was identified in the surgical specimen. Hypergastrinaemia was subsequently diagnosed and tumour localization was carried out by a new scintigraphic technique with 111In-Pentetreotide. The tumour was found to be a metastasis confined to a peripancreatic lymph node. Surgery was successful, and 6 months later the patient is still eugastrinaemic. The different imaging methods for the identification of gastrinomas are discussed together with the current therapeutic options.

Duodenal Neoplasms↗