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Biomedical subjects

P Berloco

Publications and source records attributed to P Berloco.

At least 19 recordsLinked to original sources

Alpha-SMA expression in hepatic stellate cells and quantitative analysis of hepatic fibrosis in cirrhosis and in recurrent chronic hepatitis after liver transplantation.

BACKGROUND: The alpha isotype of actin expressed by hepatic stellate cells reflects their activation to myofibroblast-like cell and has been directly related to experimental liver fibrogenesis, and indirectly to human fibrosis in chronic liver disease. AIMS: To evaluate the changes in distribution and percentage of alpha-smooth muscle actin-positive hepatic stellate cells and the correlation with the degree of the fibrosis in cirrhotic livers, as well as in patients with recurrent HCV chronic hepatitis after liver transplantation. METHODS: Human liver biopsies were divided in four groups: (1) normal livers obtained from cadaveric liver donors (n=35), (2) cirrhosis post-HBV hepatitis (n=11), (3) cirrhosis post-HCV hepatitis (n=10), and (4) post-transplant recurrent HCV chronic hepatitis (n=13). Samples were stained with anti-alpha-smooth muscle actin antibody by immunoperoxidase method and semi-quantitatively evaluated. Liver fibrosis was assessed from specimens stained with Masson's trichrome and quantified by computer image analysis. RESULTS: The percentage of alpha-smooth muscle actin-positive hepatic stellate cells was significantly higher in the HBV cirrhosis, HCV cirrhosis and post-transplant HCV recurrent hepatitis groups (36.1+/-15.2, 23.8+/-19.7 and 27.8+/-16.4%, respectively) compared to the liver donor group (2.9+/-4.0%). The alpha-smooth muscle actin-positive hepatic stellate cells to fibrous tissue ratio were significantly higher in the post-transplant recurrent HCV hepatitis group (2.36+/-1.12) compared to both the donor livers and the HCV cirrhosis groups (0.74+/-1.09 and 1.03+/-0.91, respectively). The alpha-smooth muscle actin-positive hepatic stellate cell percentage and fibrosis correlated positively in the post-transplant recurrent HCV hepatitis group and negatively in the HCV cirrhosis group. No difference in the immunohistochemical and morphometrical variables was found between the HCV cirrhosis and HBV cirrhosis groups. CONCLUSIONS: These results indirectly confirm that, in vivo, alpha-smooth muscle actin expression is a reliable marker of hepatic stellate cells activation which precedes fibrous tissue deposition even in the setting of recurrent HCV chronic hepatitis after liver transplantation, and it could be useful to identify the earliest stages of hepatic fibrosis and monitoring the efficacy of the therapy. In the presence of advanced cirrhosis other factors, rather than alpha-smooth muscle actin-positive hepatic stellate cells, may sustain fibrosis deposition.

Actins↗

Changes in coagulation-fibrinolysis balance in blood mononuclear cells and in gastric mucosa from patients with Helicobacter pylori infection.

INTRODUCTION: Helicobacter pylori and some of its virulence factors stimulate human blood mononuclear cells (MNC) in vitro to produce tissue factor (TF) and plasminogen activator inhibitor-2 (PAI-2). In this study we investigated the procoagulant-fibrinolytic potential of blood MNC in patients with H. pylori infection. In the same patients we also evaluated the coagulation-fibrinolysis profile in gastric tissue and in plasma. METHODS AND RESULTS: The production of TF and PAI-2 was evaluated in 61 patients with dyspepsia, 31 positive and 30 negative for H. pylori infection. TF expressed by MNC and PAI-2 accumulation in cell culture medium after incubation for 20 h at 37 degrees C were significantly higher in H. pylori(+) than in H. pylori(-) patients and were significantly correlated. TF and PAI-2 content in extracts of gastric mucosa was similar in the two groups whereas lower levels of tissue plasminogen activator (t-PA) and thrombomodulin (TM) antigens were found in the antrum of H. pylori(+) patients. No difference between the groups was observed in plasma thrombus precursor protein, prothrombin fragment 1+2, D-dimer, t-PA, PAI-1, TM and thrombin activatable fibrinolysis inhibitor. CONCLUSIONS: H. pylori infection is associated with functional abnormalities of blood MNC resulting in the coordinate expression of TF and antifibrinolytic activity. Changes in cell coagulation-fibrinolysis balance may represent a link between H. pylori infection and ischemic heart disease.

Adult↗

A randomized trial of steroid avoidance in renal transplant patients treated with everolimus and cyclosporine.

In this randomized trial renal transplant recipients were treated with basiliximab, everolimus 3 mg/day, low-dose CsA. At transplantation, patients were randomized to stop steroids at the seventh day (group A) or to continue oral steroids in low doses (group B). Of the 113 patients enrolled, 65 were randomized to group A and 68 to group B. All patients were followed for 2 years. During the study 28 (43%) group A patients required reintroduced corticosteroids. One patient died, in group B. The Graft survival rate was 97% in group A and 90% in group B. There were more biopsy-proven rejections in group A (32% vs 16%; P = .044). The mean creatinine clearance was 54 +/- 21 mL/min in group A vs 56 +/- 22 mL/min in group B. Mean levels of serum cholesterol tended to be lower in group A, but the difference was of borderline significance (191 +/- 91 vs 251 +/- 188 mg/dL; P = .07). Vascular thrombosis (0 vs 5) and pneumonia requiring hospitalization (2 vs 7) tended to be more frequent in group B. Only three cases of CMV infection (1 vs 2) occurred. An immunosuppressive therapy with everolimus and low-dose CsA allows one to obtain excellent renal graft survival and stable graft function at 2 years. Early interruption of steroids in patients treated with this regimen may increase the risk of acute rejection, but neither affects graft survival nor graft function, while possibly reducing the risk of hyperlipemia and vascular thrombosis. About 60% of patients given everolimus and low-dose CsA can definitively stop steroids after 1 week.

Adolescent↗

Cardiovascular and thrombophilic risk factors for idiopathic sudden sensorineural hearing loss.

BACKGROUND: In recent years there has been a significant increase in the diagnosis of sudden sensorineural hearing loss (SSHL) in western, countries with an incidence of 20 of 100,000 people affected every year. No clear causes for this disease have been found thus far, but cochlear ischemia has been hypothesized in patients in whom an infectious episode or acoustic neurinoma have been excluded. OBJECTIVES: The aim of this case-control study was to investigate a number of acquired and inherited thrombophilic risk factors [antithrombin, protein C and S; factor V (FV) Leiden, FII polymorphism; lupus anticoagulant (LA); anticardiolipin (aCL) antibodies; fasting homocysteine (Hcy); lipoprotein(a) (Lp(a)); plasminogen activator inhibitor-1 (PAI-1)] in addition to cardiovascular risk factors in patients with idiopathic SSHL (ISSHL). PATIENTS AND METHODS: We investigated 155 patients (67 male/88 female; age: 55 (range 19-79 years) with a diagnosis of ISSHL within 30 days from the onset of symptoms, and 155 controls (67 male/88 female; age 54 (range 19-78 years). Fasting Hcy levels were significantly higher in patients than in controls [11.6 (6.7-60) micromol/L vs. 8.7 (5.0-24) micromol/L] as well as PAI-1 levels [19 (2-95) mg/dL vs. 14.5 (4.0-87) mg/dL]. Lupus anticoagulant was present in 13 of 155 (8.4%) patients; 20 patients (12.9%) had positivity of aCL (four IgM and 16 IgG). In no patient was a deficiency of physiological clotting inhibitors antithrombin, protein C and protein S found. No significant differences between patients and controls were observed for Lp(a) plasma levels [111 (1-1146) mg/L vs. 103 (11-695) mg/L] and for the presence of FV Leiden (4.5% vs. 4.5%) and FII variant G20210A (3.8% vs. 3.2%). RESULTS AND CONCLUSIONS: Independent risk factors for ISSHL at the multivariate analysis (adjusted for age, sex and the traditional cardiovascular risk factors) were the positivity of aCL: OR 5.6 (95% CI 2.0-15.3); cholesterol levels within the second and third tertiles (with respect to the first tertile): T2 = OR 4.8 (95% CI 1.9-12.6)/T3 = OR 19 (95% CI 7-50.1); PAI-1 and Hcy levels within the third tertile (with respect to the first tertile): OR 20 (95% CI 7.8-78) and OR 4.0 (95% CI 2.0-8.1), respectively. These preliminary data suggest that hypercholesterolemia, hyperhomocysteinemia, elevated PAI-1 levels and anticardiolipin antibodies are associated with ISSHL, so indirectly supporting the hypothesis of a vascular occlusion in the pathogenesis of the disease.

Adult↗

Sequential treatment for Helicobacter pylori does not share the risk factors of triple therapy failure.

BACKGROUND: Predicting factors for the outcome of conventional Helicobacter pylori triple therapy have been identified. Of these, the presence of the CagA gene is a strong predictor of successful treatment. Our preliminary data show that this factor becomes irrelevant when sequential therapy is used. AIM: To identify predicting factors for the outcome of H. pylori eradication using two therapeutic schemes (triple and sequential) of equal duration (10 days). METHODS: Ninety-six patients with H. pylori infection were randomly assigned to receive one of the following therapeutic schemes: group A: rabeprazole (20 mg b.d.) plus amoxicillin (1 g b.d.) for 5 days, followed by rabeprazole (20 mg b.d.) plus tinidazole (500 mg b.d.) and clarithromycin (500 mg b.d.) for a further 5 days; group B: rabeprazole (20 mg b.d.) plus amoxicillin (1 g b.d.) and clarithromycin (500 mg b.d.) for 10 days. Age, sex, smoking, endoscopic and histological findings, and CagA and VacA status were considered as candidates for a model of multivariate analysis which used therapeutic outcome as the dependent variable. CagA and VacA status were assessed by polymerase chain reaction on DNA isolated from gastric antral specimens. RESULTS: The sequential scheme was significantly more effective than prolonged triple therapy (P < 0.05). Smoking (P < 0.001) and the absence of the CagA gene (P < 0.05) were significantly associated with the failure of triple therapy, but the effectiveness of sequential treatment was not predicted by these factors. CONCLUSION: Our data suggest that sequential therapy is not affected by bacterial and host factors which have, until now, predicted the outcome of conventional eradication treatments.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Low-dose intramuscular hepatitis B immune globulin and lamivudine for long-term prophylaxis of hepatitis B recurrence after liver transplantation.

The combination of lamivudine and hepatitis B immunoglobulins (HBIg) to prevent recurrence of HBV hepatitis has significantly improved the survival of patients transplanted for HBV-related end-stage liver disease. Generally, HBIg are administered intravenously. We evaluated the efficacy, tolerability, and cost savings of long-term intramuscular HBIg and lamivudine in 28 patients (23 men and 5 women), who received liver transplants for acute or chronic HBV-related liver disease. Twelve patients started lamivudine before and 16 at the time of liver transplantation. HBIg were administered intravenously during the first week (50 to 70,000 IU) and intramuscularly thereafter (1200 IU every 3 to 6 weeks) to maintain an HbsAb titer >100 IU/L. Mean follow-up was 20 +/- 13 months. Only one patient experienced HBV recurrence (9 months after transplantation). This patient had failed to follow the scheduled prophylaxis. Cumulative survival at 3 years was 83%. Intramuscular HBIg were well tolerated in all cases. Cost analysis comparing intramuscular vs intravenous HBIg administration showed that 39,490 Euros were saved per patient per year. These preliminary results show that low-dose intramuscular HBIg and lamivudine are efficacious and cost-effective for long-term prophylaxis of hepatitis B recurrence after liver transplantation.

Antiviral Agents↗

Helicobacter pylori strains and histologically-related lesions affect the outcome of triple eradication therapy: a study from southern Italy.

BACKGROUND: Certain evidence suggests that Helicobacter pylori strains expressing genes for cytotoxin production show a higher sensitivity than non-cytotoxic organisms to eradication treatment. No data are available on the involvement of bacterium-related lesions in different therapeutic outcomes. AIMS: (i) To investigate whether differences in eradication rates may be related to the different expression of virulent strains (cagA, vacA, iceA) in patients undergoing proton pump inhibitor-based triple therapy, and (ii) to evaluate whether therapeutic outcome may be affected by bacterium-induced gastric lesions. METHODS: One hundred and ten H. pylori-positive subjects were enrolled. H. pylori was genotyped by polymerase chain reaction. Treatment consisted of lansoprazole-amoxicillin-clarithromycin, twice daily for 1 week. Eradication was checked by urea breath test. RESULTS: The eradication rate was 70%, and the absence of cagA was associated with unsuccessful treatment. No difference between the groups with successful and unsuccessful eradication was found with regard to vacA and iceA. Lympho-epithelial lesions and fibrosis were associated with unsuccessful treatment. CONCLUSIONS: The present data confirm the importance of cagA (but not vacA and iceA) as a predictor of successful eradication. When fibrosis and lympho-epithelial lesions are present, therapy appears to be less effective. Therefore, these histological features may be involved in an unsuccessful therapeutic outcome.

Adult↗

Demonstration of a direct stimulatory effect of bile salts on rat colonic epithelial cell proliferation.

BACKGROUND: Despite the clear demonstration that an increase in faecal bile salt concentration can augment colonocyte proliferation, it is still controversial whether bile salts act on these cells as direct mitogens or by inducing a damage-related proliferative response. The goal of this study was to define the mechanism mediating the proliferative effect of bile salts on rat colonocytes. METHODS: Faecal bile salt concentration was increased by feeding rats on diets enriched with either bile salts or fats. Colonic mucosa proliferating cell nuclear antigen (PCNA) expression, histology and apoptosis, and faecal water cytolytic activity were evaluated to assess proliferation and direct or indirect signs of mucosal damage. RESULTS: Compared to standard diet, chenodeoxycholate-, deoxycholate- and fat-enriched diets produced a significant increase in both faecal water total bile salt concentration (46.0 versus 124.1, 145.9 and 498.5 micromol/L, respectively) and percentage of PCNA-positive nuclei (30.5, versus 37.7, 33.9 and 47.1, respectively) that appeared significantly correlated (r = 0.8; P < 0.001). Chenodeoxycholate and deoxycholate fed animals showed colonic mucosa histology and faecal water cytolytic activity similar to controls, with a significantly reduced apoptotic index. Rats fed on high fat diet, however, showed a mild inflammatory infiltrate associated with an increased apoptosis and faecal water cytolytic activity, all conditions not apparently determined by the increased faecal water total bile salt concentration. CONCLUSIONS: The results obtained in this study demonstrate that bile salts act as direct mitogens on colonic epithelial cells.

Animals↗

Detection of T suppressor cells in patients with organ allografts.

Specific immunosuppression of host's immune response to donor HLA antigens has been a major goal to clinical transplantation. Recent evidence has been accumulating to show that a distinct population of T cells expressing the CD8(+) CD28(-) phenotype display suppressor function and inhibit Th activation and proliferation by modulating the APC function. To assess the presence of Ts in transplant recipient's circulation, we have developed a flow cytometry method that measures the expression of costimulatory molecules on donor APC exposed to recipient Th and Ts. Our results demonstrate that quantitation of the capacity of CD8(+) CD28(-) T cells from patient circulation to suppress the activation of costimulatory molecules (CD80, CD86) on donor APC offers a reliable tool for monitoring specific immunosuppression against the graft in solid organ transplantation.

Antigen-Presenting Cells↗

Use of macroporous polypropylene filter to allow identification of bacteria by PCR in human fecal samples.

The detection of pathogenic bacteria directly in human fecal specimens by PCR, requires removal of PCR-inhibitory substances. To investigate whether five different macroporous filters (polypropylene, nylon, polyester, polyethylene, fluorocarbon) could retain polysaccharides, major PCR inhibitors, an in vitro model and human fecal samples were used. The in vitro model consisted of Xanthum gum solutions (3 mg/ml PBS), a bacterial polysaccharide, to which Helicobacter pylori cells were added. Fecal samples from healthy volunteers were spiked with H. pylori and Mycobacterium paratuberculosis cells. Polysaccharide concentrations were significantly reduced only by the polypropylene but not by the other filters. Accordingly, both Xanthum gum solutions and spiked fecal specimens became PCR positive only after filtration with the polypropylene filter. We conclude that this filter can be used to prepare a bacterial DNA template suitable for PCR analysis from human feces.

Bacteria↗

Antioxidant effect of short-term hormonal treatment in postmenopausal women.

OBJECTIVES: Recent studies have shown that estrogens alone or in association with progestins can exert an antioxidant effect on Low-Density Lipoprotein (LDL) and lipids of platelet membranes. It has been demonstrated that the oxidative modification of LDLs also involving the formation of lipid peroxides, exerts several biological effects that may contribute to the onset and progression of cardiovascular diseases. Therefore, the aim of our study was to evaluate the effect of short-term treatment with oral estrogens alone and estrogens plus progestin on endogenous and copper-induced serum levels of lipid peroxides in postmenopausal women. METHODS: Thirty-nine postmenopausal women were randomly divided into three groups: group I was treated with oral conjugated equine estrogens (CEE) for 21 days; group II received oral CEE for 21 days and, after 14 days of this treatment, 5 mg/day of medrogestone was added for 7 days; group III did not receive any therapy (controls). Endogenous and copper-induced serum levels of lipid peroxides were determined before and after 21 days of treatment in the two treated groups and in the control group. RESULTS: The serum endogenous levels of lipid peroxides in postmenopausal women did not change after short-term treatment with hormone replacement therapy. Moreover, copper-induced serum levels of lipid peroxides significantly decreased after therapy in both groups I and II. CONCLUSIONS: Our data show that hormone replacement therapy (HRT) inhibits lipid peroxidation and may play a role in preventing cardiovascular diseases.

Cardiovascular Diseases↗

Polyamine profile in human gastric mucosa infected by Helicobacter pylori.

BACKGROUND: Several studies have demonstrated increased gastric epithelial cell proliferation associated with Helicobacter pylori infection, which is reversed after bacterium eradication. Among the substances involved in cell proliferation and differentiation, polyamines are a group of polycations found in high concentrations both in normal and neoplastic cells. AIMS: Of the study were: a) to examine the influence of Helicobacter pylori infection on the polyamine profile in the gastric antrum and body, by comparing infected, to uninfected, patients, b) to evaluate the effect of successful and unsuccessful bacterium eradication on polyamine levels. PATIENTS AND METHODS: Twenty-six consecutive dyspeptic patients (20 Helicobacter pylori positive and 6 Helicobacter pylori negative) undergoing gastroscopy were enrolled. Polyamines were evaluated in antral and body biopsies by High Performance Liquid Chromatography. RESULTS: Antral and body biopsies from Helicobacter pylori positive patients contained higher polyamine levels than those from Helicobacter pylori negative subjects. In Helicobacter pylori positive patients, the baseline polyamine levels were higher in the antrum than in the body. In Helicobacter pylori negative subjects, levels in the two stomach regions were similar. After therapy, polyamine levels decreased in patients with successful eradication, whereas these levels remained unchanged in patients in whom infection persisted. CONCLUSIONS: These findings indicate enhanced antral cellular proliferation linked to the presence of Helicobacter pylori and add weight to the postulation of an association between Helicobacter pylori infection and increased risk of neoplastic changes in gastric antral mucosa. Differences in antral and body levels of polyamines may also be considered as a further indication of the different mucosal reactivity between the two regions of the stomach towards bacterial invasion.

Adolescent↗

[A case of multifocal inflammatory pseudotumor of the liver].

INTRODUCTION: The inflammatory pseudotumor (IPT) of the liver is a tumor-like lesion of unknown etiology and pathogenesis. Non infectious by definition the lesion is considered to be a long-lasting inflammatory process. CASE: In this report we describe a multifocal liver pseudotumor of a 52 year man who underwent a selective hepatectomy for a clinical and radiological suspicion of a liver cell carcinoma. RESULTS: Grossly the masses consisted of rubbery grey-yellowish nodules well-circumscribed from the liver parenchyma. Histologic examination revealed a double shaped cellular population surrounded by a thin rim of collagen fibres. The main population consisted of fibroblasts and histiocytes with no atypias or mitoses, arranged in a storiform or fascicular pattern; the second population consisted of a mixed population of lymphocytes, plasma cells, neutrophils and monocytes. Fibroblasts and histiocytes revealed diffuse positive immunostaining for vimentin and focal immunostaining for cytokeratin and desmin. The histiocytes were also CD68, CD18, CD14 and CD4 positive. CONCLUSIONS: Our case reveals same histological and immunohistochemical features already reported in literature. Primary and metastatic tumors involving the liver need to enter in the differential diagnosis but IPT lacks features of malignancy and the cell population is mixed. Although there is no specific marker for this lesion in cases featuring malignancy immunohistochemistry may be useful for a differential diagnosis: S-100 in cases of neurofibrosarcomas, actin and myosin for rhabdomyosarcomas, cytokeratin for epithelial tumors.

Biomarkers↗

Modulation of rat hepatocyte proliferation by bile salts: in vitro and in vivo studies.

In this study, the stimulatory effect of bile salts (BS) was evaluated both in vitro, using hepatocyte primary cultures, and in vivo, in normal and 40% partially hepatectomized rats previously fed on BS-enriched diets for 4 weeks. In vitro results show that conjugated cholate (CA) and chenodeoxycholate (CDCA) augmented proliferative activity in rat hepatocytes cultured in absence of mitogens, whereas conjugated deoxycholate (DCA), and ursodeoxycholate (UDCA) did not have any significant effect. None of these BSs increased significantly the replicative response induced by submaximal concentrations of epidermal growth factor (EGF). In vivo, at the end of dietary treatment all animals fed on CA or DCA but not those fed on either CDCA, or UDCA, or tauroursodeoxycholate (TUDCA) developed cholestatic hepatitis and a burst of damage-induced hepatocyte proliferation. After 40% partial hepatectomy (PH), CA- and DCA-treated groups underwent a deterioration of cholestatic hepatitis. On the other hand, in CDCA-, and UDCA-, and TUDCA-treated groups liver histology, serum glutamic pyruvic transaminase (SGPT) and cholestasis indices did not change significantly compared with controls. As far as the proliferative activity, a significant increase was observed not only in CA and DCA but also in UDCA- and TUDCA-fed groups compared with controls, whereas a slight decrease was observed in CDCA-treated animals. In conclusion, our data indicate that conjugated BSs had only a modest stimulatory effect on hepatocyte proliferation in vitro. However, in vivo, in PH rats, UDCA or TUDCA treatment determined a further increase of hepatocellular proliferation not attributable to hepatotoxic effects. Our result suggest that modifications of bile acid pool could modulate hepatocellular proliferation.

Animals↗

alpha-Tocopherol and beta-carotene serum levels in post-menopausal women treated with transdermal estradiol and oral medroxyprogesterone acetate.

Estrogens exert a protective effect against atherosclerosis. It is well known that hormone replacement therapy (HRT) can effectively decrease LDL-cholesterol and increase HDL-cholesterol and Apo-Al serum levels. Some recent studies have suggested that estrogens alone or in association with progestins may exert an antioxidant effect on lipids. Besides sex steroids, also vitamins exert an antioxidant effect on LDL and may preserve the endogenous antioxidants of LDL. The aim of our study was to evaluate whether HRT can improve alpha-tocopherol and beta-carotene serum levels in post-menopausal women. Fifteen postmenopausal women with climacteric symptoms were treated with 50 micrograms/24 h estradiol transdermally applied twice a week for 21 days. A daily dose of 10 mg oral medroxyprogesterone acetate was added for 12 days in each treatment cycle. This therapy lasted 6 months. A significant reduction was found in total cholesterol and LDL-cholesterol after treatment. Besides, our study has shown that alpha-toc/LDL and beta-car/LDL ratios significatively increased after treatment, while alpha-tocopherol and beta-carotene serum levels did not change significantly after therapy. These preliminary findings suggest that HRT can preserve the content of alpha-tocopherol and beta-carotene in LDL particles and keep the LDL in a reduced antioxidant state.

Administration, Cutaneous↗