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Biomedical subjects

A Mele

Publications and source records attributed to A Mele.

At least 19 recordsLinked to original sources
PubMed2006

Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep.

We have recently reported that in pigs with chronic myocardial ischemia heart transfection with a plasmid encoding the 165 isoform of human vascular endothelial growth factor (pVEGF165) induces an increase in the mitotic index of adult cardiomyocytes and cardiomyocyte hyperplasia. On these bases we hypothesized that VEGF gene transfer could also modify the evolution of experimental myocardial infarct. In adult sheep pVEGF165 (3.8 mg, n=7) or empty plasmid (n=7) was injected intramyocardially 1 h after coronary artery ligation. After 15 days infarct area was 11.3+/-1.3% of the left ventricle in the VEGF group and 18.2+/-2.1% in the empty plasmid group (P<0.02). The mechanisms involved in infarct size reduction (assessed in additional sheep at 7 and 10 days after infarction) included an increase in early angiogenesis and arteriogenesis, a decrease in peri-infarct fibrosis, a decrease in myofibroblast proliferation, enhanced cardiomyoblast proliferation and mitosis of adult cardiomyocytes with occasional cytokinesis. Resting myocardial perfusion (99mTc-sestamibi SPECT) was higher in VEGF-treated group than in empty plasmid group 15 days after myocardial infarction. We conclude that plasmid-mediated VEGF gene transfer reduces myocardial infarct size by a combination of effects including neovascular proliferation, modification of fibrosis and cardiomyocyte regeneration.

Animals↗
PubMed2006

Early impairment of hepatitis C virus specific T cell proliferation during acute infection leads to failure of viral clearance.

BACKGROUND AND AIMS: Cellular mediated immunity (CMI) is thought to play a key role in resolution of primary hepatitis C virus (HCV) infection. However, CD4+ and CD8+ T cell responses are also generated during acute infection in individuals who become chronic, suggesting that they developed a defective CMI. The aim of this study was to verify if and when such immune dysfunction is established by measuring the breadth, magnitude, function, and duration of CMI in a large cohort of subjects during the natural course of acute HCV infection. METHODS: CMI was comprehensively studied by prospective sampling of 31 HCV acutely infected subjects enrolled at the onset of infection and followed for a median period of one year. RESULTS: Our results indicated that while at the onset of acute HCV infection a measurable CMI with effector function was detected in the majority of subjects, after approximately six months less than 10% of chronically infected individuals displayed significant CMI compared with 70% of subjects who cleared the virus. We showed that progressive disappearance of HCV specific T cells from the peripheral blood of chronic patients was due to an impaired ability to proliferate that could be rescued in vitro by concomitant exposure to interleukin 2 and the antigen. CONCLUSION: Our data provide evidence of strong and multispecific T cell responses with a sustained ability to proliferate in response to antigen stimulation as reliable pharmacodynamic measures of a protective CMI during acute infection, and suggest that early impairment of proliferation may contribute to loss of T cell response and chronic HCV persistence.

Acute Disease↗
PubMed2006

Interactions of alpha-tocopherol with biomembrane models: binding to dry lecithin reversed micelles.

The state of alpha-tocopherol (Vitamin E) in solutions of dry lecithin reversed micelles dispersed in an apolar medium has been investigated as a function of the Vitamin E to surfactant molar ratio (RVE) at fixed surfactant concentration by FT-IR, 1H NMR and SAXS with the aim to emphasize the role played by anisotropic intermolecular interactions and confinement effects as driving forces of its partitioning between apolar bulk solvent and polar nanodomains and of mutual Vitamin E/reversed micelle effects. It has been found that its binding strength to reversed micelles, triggered by steric and orientational constrains, is mainly regulated by specific interactions between the hydrophilic groups both of Vitamin E and surfactant. Moreover, the RVE dependence of the Vitamin E distribution constant and of the micellar size suggest that the inclusion of increasing amounts of Vitamin E in reversed micelles involves substantial changes in the structural and dynamical properties of the micellar aggregates. The occurrence of mutual effects and the partitioning of Vitamin E between hydrophilic/hydrophobic interfaces and apolar domains allow to infer some important biological implications concerning the capacity of Vitamin E to scavenge free radicals arising from hydrophilic and/or hydrophobic domains, possible variations of its local reactivity respect to that observed in bulk as well as its significant influence on the stability of biomembranes.

Carbon Tetrachloride↗
PubMed2006

Local cutaneous arachnidism: a report of three cases and their management.

Bites from Loxosceles spiders can cause few symptoms to gangrenous skin necrosis or even death. To date, the treatment of the violin spider bite is largely unsatisfactory. Although no specific therapy exists, it has been suggested that heparin, steroids, dapsone, experimental antivenin and/or surgical excision may be beneficial. Three rare cases of suspected spider bite and their surgical treatment are reported. On the basis of geographical area, anamnesis and clinical symptoms, we suppose Loxoceles rufescens responsible for these bites.

Aged↗
PubMed2006

Exposure to HAV infection in patients with chronic liver disease in Italy, a multicentre study.

We carried out a multicentre study on 2830 patients with chronic liver disease from 79 liver units (25 in northern, 24 in central and 30 in southern Italy) to evaluate naturally acquired immunity against hepatitis A virus (HAV) in relation to age, sex, geographical area of origin and entity of liver disease, and to define the strategy for specific vaccination. Antibody to HAV (anti-HAV) was detected in 1514 (53.5%) of the 2830 patients tested; the prevalence was 50.4% in males and 59.1% in females. Both in central and southern Italy the prevalence of anti-HAV positive subjects increased with increasing age from 43.3 and 44.7%, respectively, in the 0-30-year-old subjects to 80.1 and 68.3%, respectively, in those aged over 60 years. The overall prevalence was much lower in northern Italy, as were the variations from one age group to another, from 28.4% in the 0-30-year-old subjects to 38% in those aged over 60 years. 40.6% of patients with cirrhosis lacked naturally acquired protection against HAV; this percentage was higher in northern (60.5%) than in central (34.9%, P < 0.0001) and southern Italy (27.6%, P < 0.0001). The high prevalence of patients in Italy with chronic hepatitis or cirrhosis who lack naturally acquired immunity to HAV warrants the implementation of vaccination programmes against hepatitis A in such patients.

Adolescent↗
PubMed2005

Validity and reliability of the Italian version of the Chronic Liver Disease Questionnaire (CLDQ-I) for the assessment of health-related quality of life.

BACKGROUND: The Chronic Liver Disease Questionnaire is a specific health-related quality of life assessment designed for patients with liver diseases. AIM: The aim of this paper is to report on the validity, reliability and sensitivity to change of the Italian version (Chronic Liver Disease Questionnaire-I) in subjects with HCV infection. SUBJECTS: The Chronic Liver Disease Questionnaire-I was administered to 350 subjects with HCV infection together with the World Health Organization Quality of Life Assessment, abbreviated version, a generic quality of life assessment. METHODS: The instrument was translated from English, backtranslated and reviewed in focus groups in the framework of a large multicentre study. Exploratory factor analysis identified five factors accounting for 65% of the variance of Chronic Liver Disease Questionnaire-I items and only partially overlapping with those found in the original version. RESULTS: The Chronic Liver Disease Questionnaire-I proved to discriminate between subjects with and without comorbid diseases at baseline (t-test = 3.59, p < 0.001). Test-retest reliability was moderate (ICC = 0.60). The Chronic Liver Disease Questionnaire-I was sensitive to change in patients who deteriorated after one month of treatment. Change in the overall Chronic Liver Disease Questionnaire-I score in deteriorated patients was correlated with changes in World Health Organization Quality of Life Assessment, abbreviated version scores in the physical, psychological and environment, but not in the social area. CONCLUSIONS: The Italian version of Chronic Liver Disease Questionnaire is a valid and reliable instrument to be used in cross-sectional and longitudinal studies.

Chronic Disease↗
PubMed2005

Screening for hepatocellular carcinoma.

BACKGROUND AND AIM: The incidence of hepatocellular carcinoma is high among cirrhotic patients, ranging from 2 to 3% in western cohorts and 6-11% in eastern cohorts. Although only one randomised trial has been performed, clinical practice generally uses periodic screening to detect hepatocellular carcinoma in cirrhotic patients. We reviewed the scientific literature on hepatocellular carcinoma screening. MATERIALS AND METHODS: Evaluation of studies identified through MEDLINE and EMBASE (1990-May 2003). RESULTS: The available screening tests to detect hepatocellular carcinoma are alpha-fetoprotein (cut-off: 20 ng/ml) and ultrasound, which are generally combined. The reported sensitivity and specificity are 50-85% and 70-90%, respectively. An estimated doubling time of about 6 months has led to the use of an interval of 6 months between screenings. Based on the risk of hepatocellular carcinoma, cirrhotic patients are considered as the target population. Screening seems to detect smaller and more frequently unifocal hepatocellular carcinoma; the residual liver function is important for determining the eligibility for effective treatment (resection); hence the prevention is more effective for patients with well-compensated cirrhosis. The survival estimated by non-randomised studies is slightly longer for patients with screening-detected hepatocellular carcinoma, compared to those with clinically detected hepatocellular carcinoma, although few studies have accounted for 'lead time bias'. CONCLUSIONS: Although screening for the early detection of hepatocellular carcinoma has become quite common in clinical practice, its effectiveness remains controversial. Observational studies that have taken into account lead time bias suggest that survival is greater for patients with screening-detected hepatocellular carcinoma, yet the eligibility for effective treatments is low. Considering that only one randomised controlled trial has been conducted, it is crucial to standardise the screening schedule and to evaluate prevention programmes.

Carcinoma, Hepatocellular↗
PubMed2005

Feasibility of vaccination in preventing secondary cases of hepatitis A virus infection.

Although the secondary transmission of hepatitis A virus (HAV) infection is preventable through vaccination, it is not known whether the vaccination of household contacts is feasible. To this end, we conducted a prospective cohort study among the household contacts, 40 years of age or less, of all persons infected with primary HAV infection (index cases) and admitted to eight hospitals in southern Italy within 7 days of onset. Household contacts were vaccinated, and serum samples were taken at vaccination and after 14 and 45 days. Secondary cases were defined as those with IgM seroconversion occurring at least two weeks after enrollment. Coprimary cases were those assumed to have had the same exposure as the index case. Susceptible cases were those who were negative for both IgG and IgM. A total of 495 household contacts participated (acceptance rate of 65%); 65% were vaccinated within 4 days of admission of the index case and 95% within 7 days. At enrollment, 196 (39.6%) household contacts were immune (IgG-positive serum). During follow-up, 19 (3.8%) were IgM-positive: 13 (2.6%) were coprimary cases and 6 (1.2%; 95% CI: 0.2-3.2) secondary cases (5 identified at 14 days from vaccination and 1 at 45 days). Of the 241 susceptible cases, 192 (79.7%) had developed IgG antibodies at 14 days and only 3 (1.2%) did not develop IgG antibodies at 45 days. The 65% acceptance rate and the finding that 95% of the participating household contacts were vaccinated within 7 days of the index case's hospitalization indicate that timely vaccination is indeed feasible. The necessity of returning for the collection of blood samples probably decreased the acceptance rate.

Adolescent↗
PubMed2005

Clinical and molecular characterization of chronic hepatitis B in Albania: a country that is still highly endemic for HBV infection.

Albania is a Mediterranean country, still with a high endemicity level of hepatitis B virus (HBV) infection. The chronic hepatitis B profile was characterized in this geographical area and used as a model to investigate the impact of endemicity level on the prevalence of the two major forms of chronic hepatitis B (HBeAg-positive and HBeAg-negative chronic hepatitis B). A cross-sectional study was conducted among 62 chronic hepatitis B patients consecutively admitted to the most important tertiary health care center for the diagnosis and treatment of liver disease in Albania. HBV-DNA was measured with an in-house PCR with a sensitivity of 10(4) copies/ml which uses primers encompassing the pre-core/core region. PCR products were subjected to sequencing and oligohybridization assay. Of the 62 patients, 75.8% had HBeAg-negative chronic hepatitis B. Genotype D was found in all 39 patients with detectable HBV viremia, for whom the heterogeneity of the region modulating HBeAg expression was assessed. Basic core promoter (BCP) mutations (1762/1764) were observed more often in anti-HBe-positive and older patients. In more than 90% of the HBeAg-negative chronic hepatitis B patients with detectable viremia, HBV that carries the G to A pre-core mutation at nucleotide 1896 was found. Patients with HBeAg-positive chronic hepatitis B were younger than HBeAg-negative chronic hepatitis B patients, and for symptomatic and asymptomatic liver-disease patients, the age of peak prevalence was at least 10 years lower for HBeAg-positive chronic hepatitis B patients. In conclusion, the virological and clinical pattern of chronic hepatitis B in Albania is similar to that observed in other Mediterranean countries; it seems to be independent of the HBV endemicity level.

Adult↗
PubMed2004

Characteristics of liver cirrhosis in Italy: results from a multicenter national study.

BACKGROUND: In 1992, the characteristics of liver cirrhosis in Italy were assessed in a cross-sectional study among 1829 cirrhosis patients attending 21 tertiary centres. AIM: To evaluate the characteristics of cirrhosis patients 9 years later. PATIENTS: A total of 2185 consecutive cirrhosis patients were enrolled over a 6-month period in 79 hospitals located throughout Italy, randomly selected by means of systematic cluster sampling. RESULTS: The main agent associated with cirrhosis was hepatitis C virus, which was found in 69.9% of the patients and was the only etiologic factor in 51.1% of the patients. Hepatitis B surface antigen was present in the serum of 13.0% of the cases (in 7.3%, it was the only etiologic factor). A history of alcohol abuse was found in 31.9% of the cases (12.4% without viral infection). Patients with hepatitis C virus-related cirrhosis were older (mean age of 64.4 years) and more likely to be female (male:female ratio of 0.7), compared to patients with other pathogenic factors. Virus-related cirrhosis was more likely to be observed in southern Italy, whereas alcohol-related cirrhosis was prevalent in the North. CONCLUSIONS: As found in the 1992 study, the results of the present study show that in Italy, liver cirrhosis is mainly associated with hepatitis C virus infection, reflecting the high prevalence of this infection in the general population.

Aged↗
PubMed2004

The aetiology of chronic hepatitis in Italy: results from a multicentre national study.

BACKGROUND: No recent national-level data on the aetiology of chronic hepatitis are available in Italy. AIM: To evaluate the current aetiology of chronic hepatitis in Italy. PATIENTS: A total of 6210 chronic hepatitis patients (both prevalence and incident cases) consecutively admitted to 79 hospitals located throughout Italy were enrolled over a 6-month period in 2001. The hospitals were randomly selected through systematic cluster sampling. RESULTS: The main agent associated with chronic hepatitis was hepatitis C virus, which was found in 76.5% of the patients (in 62.6% it was the only aetiologic factor). Hepatitis B surface antigen was present in the serum of 12.2% of the cases (in 9.2% it was the only aetiologic factor). Hepatitis B e antigen and hepatitis Delta were detected in 16.6% and 7.0%, respectively, of hepatitis B surface antigen-positive patients. A history of alcohol abuse was found in 19.2% of the cases (5.5% without viral infection). Autoimmune hepatitis and inborn metabolic disorders were extremely rare. The prevalence of hepatitis C virus-related cases was significantly lower in incident cases, compared to prevalent cases (55.1% versus 65.0%; p < 0.01). The mean alanine aminotransferase level was significantly higher in hepatitis B surface antigen-positive patients, compared to hepatitis B surface antigen-negative patients. The histology was less severe in non-viral-related cases. CONCLUSIONS: Hepatitis C virus is the most important pathogenic factor for chronic hepatitis in Italy; however, the comparison between prevalent and incident cases suggests that this infection will play a less important role in the future. A comparison with previous reports shows that both hepatitis B virus-related and hepatitis Delta virus-related cases are decreasing.

Adult↗
PubMed2004

Effectiveness of immune globulins in preventing infectious hepatitis and hepatitis A: a systematic review.

OBJECTIVE: To assess the effectiveness and safety of immune globulins in preventing infectious hepatitis and hepatitis A. STUDY DESIGN: Systematic review with meta-analysis. DATA SOURCES: We searched the Cochrane Library, MEDLINE, EMBASE, Biological Abstracts and Science Citation Index to December 2002. Vaccine manufacturers were contacted for additional data. REVIEW METHODS: We included randomised controlled trials comparing effectiveness of hepatitis A immune globulins with no intervention or placebo, and carried out a meta-analysis. RESULTS: We included six studies (two in Russian). Tested immune globulins show higher effectiveness than placebo or do-nothing against infectious hepatitis both in primary prevention and in prevention after exposure (effectiveness 83%; RR: 0.17; 95% CI: 0.15-0.19; and effectiveness 69%; RR: 0.31; 95% CI: 0.20-0.47, respectively). We found considerable heterogeneity among studies, possibly due to different methodology, background rates of disease and immune globulins dosage and concentrations. No safety data were reported in the studies. CONCLUSIONS: Immune globulins are efficacious in preventing infectious hepatitis and hepatitis A, but included studies do not report data about their safety. Average length of passive protection was three months. Given the notable heterogeneity of performance of immune globulins, short protection conferred and absence of trial safety data, the only indications for the use of immune globulins may be in situations in which inadequate supplies of vaccine are available or when the eight-day window of opportunity for vaccine use is past.

Chi-Square Distribution↗
PubMed2004

Nucleus accumbens dopamine receptors in the consolidation of spatial memory.

Nucleus accumbens dopamine is known to play an important role in motor activity and in behaviours governed by drugs and natural reinforcers, as well as in non-associative forms of learning. At the same time, activation of D1 and D2 dopamine receptors has been suggested to promote intracellular events related to neural plasticity. Therefore, in this study we wished to investigate the role of the two classes of dopamine receptors within the nucleus accumbens on the consolidation of spatial information. On day 1, CD1 male mice were placed in an open field containing five different objects and, immediately after three sessions of habituation, the animals were focally injected within the nucleus accumbens with either the D1 antagonist SCH 23390 (12.5, 25 or 50 ng/side), or the D2 antagonist sulpiride (25, 50, 75 or 100 ng/side). Twenty-four hours later the ability of mice to discriminate an object displacement was assessed. Both the D1 and the D2 antagonists impaired the ability of mice to detect the spatial change. If the highest doses of the two antagonists were injected 2 h after the end of the last of the habituation sessions, no effect was observed in the reactivity to spatial change examined 24 h later. These data demonstrate that activation of both D1 and D2 receptors within the accumbens is necessary in the early stages of the consolidation of spatial information. The data are discussed in terms of involvement of nucleus accumbens dopamine in information processing in the absence of explicit reinforcers.

Animals↗
PubMed2004

Hippocampal gene expression is modulated by hypergravity.

We used the cDNA microarray technique to monitor simultaneously possible changes induced by hypergravity in the expression level of thousands of hippocampal genes. We tested the mRNA level of about 5000 genes in the hippocampus of mice subjected to 1.09 g (1g) or to 1.85 g (2g) for five repeated 1-h daily rotations in a centrifuge (g = 9.81 m/s2). Data were compared with those obtained for mice kept stationary (C). The ratios 1g/C and 2g/C identified genes affected by rotation and rotation + hypergravity, respectively, whereas 2g/1g ratio identified those affected by hypergravity. We found that about 200 genes were affected by rotation and/or rotation + hypergravity. Almost all the genes affected by rotation + hypergravity were up-regulated, only five being down-regulated. The modulated genes code for proteins involved in a wide range of cellular functions (DNA/RNA metabolism, protein processing, intermediate metabolism, cytoskeleton and motility, cell cycle and apoptosis, signal transduction, neuronal structure/function), suggesting that rotation + hypergravity may affect several aspects of the hippocampal function in order to compensate for environmental changes. Six genes directly or indirectly involved in synaptic transmission and plasticity (proSAAS, neuroblastoma ras oncogene, ESTs moderately similar to thymosin beta-10, syndet, inhibin beta E and Ngfi-A binding protein 2) were found to be significantly modulated by hypergravity and unaffected or only slightly affected by rotation. The modulation by hypergravity of these genes suggests that this stimulus might induce plastic remodelling of the hippocampal circuits, possibly both at structural and functional level.

Animals↗
PubMed2004

Multispecific T cell response and negative HCV RNA tests during acute HCV infection are early prognostic factors of spontaneous clearance.

BACKGROUND/AIMS: Hepatitis C virus (HCV) infection results in a high frequency of chronic disease. The aim of this study was to identify early prognostic markers of disease resolution by performing a comprehensive analysis of viral and host factors during the natural course of acute HCV infection. METHODS: The clinical course of acute hepatitis C was determined in 34 consecutive patients. Epidemiological and virological parameters, as well as cell mediated immunity (CMI) and distribution of human leukocyte antigens (HLA) alleles were analysed. RESULTS: Ten out of 34 patients experienced self-limiting infection, with most resolving patients showing fast kinetics of viral clearance: at least one negative HCV RNA test during this phase predicted a favourable outcome. Among other clinical epidemiological parameters measured, the self-limiting course was significantly associated with higher median peak bilirubin levels at the onset of disease, and with the female sex, but only the latter parameter was independently associated after multivariate analysis. No significant differences between self-limiting or chronic course were observed for the distribution of DRB1 and DQB1 alleles. HCV specific T cell response was more frequently detected during acute HCV infection, than in patients with chronic HCV disease. A significantly broader T cell response was found in patients with self-limiting infection than in those with chronic evolving acute hepatitis C. CONCLUSION: The results suggest that host related factors, in particular sex and CMI, play a crucial role in the spontaneous clearance of this virus. Most importantly, a negative HCV RNA test and broad CMI within the first month after onset of the symptoms represent very efficacious predictors of viral clearance and could thus be used as criteria in selecting candidates for early antiviral treatment.

Adult↗