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Biomedical subjects

F Bortolotti

Publications and source records attributed to F Bortolotti.

At least 73 records · Page 4Linked to original sources
PubMed1996

Long-term persistence of hepatitis B virus DNA in the serum of children with chronic hepatitis B after hepatitis B e antigen to antibody seroconversion.

To evaluate the prevalence and duration of viremia in relation to the features of liver disease, we investigated hepatitis B virus (HBV) DNA by the polymerase chain reaction in the serum of 39 children with chronic hepatitis B, after hepatitis B e antigen to antibody seroconversion. During a mean observation period of 8.2 +/- 3.8 years after seroconversion, all patients were asymptomatic; 36 had persistently normal alanine aminotransferase levels, and three had occasional mild alterations. Liver histology, checked in 21 patients, showed persistent hepatitis in nine, fibrosis in 10, and cirrhosis in two cases. HBV DNA was always undetectable by dot blot hybridization. Five children eventually cleared hepatitis B surface antigen, including one with cirrhosis who developed liver cancer at 19 years. HBV DNA was detected by polymerase chain reaction in 87% of children within 5 years of follow-up, in 58% of cases 6-10 years after seroconversion (p < 0.001), and in 50% of patients investigated later. Long-term viremia was found in two patients (40%) who cleared HBsAg, including the one who developed liver cancer. The chances of clearing viremia during follow-up were higher in children with acute hepatitis at the onset of illness (86%) than in those with asymptomatic onset (37%; p < 0.05). Our results show that low levels of HBV viremia, probably reflecting low levels of virus replication, persist for several years in children with chronic hepatitis B after hepatitis B e antigen to antibody seroconversion and remission of liver disease, even after the clearance of hepatitis B surface antigen. Persistent replication could support mild biochemical alterations and inflammatory liver lesions. It could allow late reactivation of liver disease and may play a role in the development of carcinoma.

Alanine Transaminase↗
PubMed1996

Long-term interferon-alpha treatment of children with chronic hepatitis delta: a multicentre study.

We assessed the efficacy of prolonged interferon-alpha (IFN) therapy in children with chronic hepatitis caused by hepatitis delta virus (HDV) by treating 26 paediatric cases with IFN-alpha 2b (5 MU m-2, then 3 MU m-2 three times weekly for 12 (medium-term group MTG) or 24 months (long-term group, LTG). Compliance and tolerability were acceptable. At the end of therapy a complete biochemical response [normalization of alanine aminotransferase (ALT)] occurred in 12 children (5/13 in MTG and 7/13 in LTG). A relapse occurred after stopping IFN in 10 cases (five in MTG and five in LTG). Two patients from the LTG had normal liver function tests during 12 months of follow-up. Six of the eight hepatitis B e antigen (HBeAg) positive children lost HBeAg, while all six hepatitis B virus (HBV) DNA positive patients lost HBV DNA during treatment. HBeAg reappeared later in two children. HDV RNA, present in 10/10 cases of MTG before treatment, persisted after 12 months IFN therapy in 3/10. One year after stopping therapy, 8/10 patients were again HDV RNA positive. Two children cleared hepatitis delta antigen (HDVAg) from the liver. No significant improvements in liver histology were seen in both groups. Our experience suggests that IFN-alpha treatment in children with chronic type D hepatitis has a transient effect, and long-term treatment does not appear to induce a greater therapeutic benefit in terms of biochemical and virological response.

Adolescent↗
PubMed1996

Hepatitis C virus genotypes in chronic hepatitis C of children.

Several hepatitis C virus (HCV) genotypes have been recently identified and genotype 1b has been correlated with severe liver disease and a poor response to interferon therapy. HCV infection in children is an interesting model for evaluation of the relationship between HCV genotypes and liver disease, because of its relatively short duration and the infrequent association with confounding cofactors. We have investigated HCV genotypes, using a dot-blot hybridization assay with genotype-specific probes, in 36 Italian children with chronic hepatitis C who were otherwise well and had no other underlying disease. Only four patients were symptomatic; liver histology, obtained in 33 patients, showed minimal hepatitis in 17 and mild chronic hepatitis in 16. Infection with HCV genotype 1b was found in 55.5% of patients, with a peak prevalence of 83% in children from southern Italy (P < 0.05 vs other regions). The remaining children were infected with HCV genotype 1a (16.6%), genotype 2 (11.1%), and mixed (10.9%) or undetermined (2.7%) genotypes. In one patient, HCV viraemia was never detected. There was no statistically significant correlation between genotype and age, sex, source of infection, alanine aminotransferase pattern and histological activity index. These results indicate that genotype 1 b is widespread among Italian children with chronic hepatitis C, although with significant geographical variations. It is not associated with a more severe liver disease, therefore suggesting that the greater severity of liver disease recently reported in adults could reflect the cumulative effects of disease duration and of interfering cofactors.

Adolescent↗
PubMed1995

Hepatitis C virus infection in Italian intravenous drug users: epidemiological and clinical aspects.

The epidemological and clinical features of hepatitis C virus infection have been evaluated in a cohort of 227 intravenous drug users enrolled at a drug dependence treatment center in the Veneto area in 1992-1993 and followed periodically. Hepatitis C virus infection was detected using second-generation anti-HCV ELISA in 171 (75%) subjects at enrollment. Anti-HCV seropositivity correlated with: a) the duration of drug abuse: 91% of intravenous drug users injecting for more than 8 years were seropositive as compared to 40% of those with a history of abuse lasting 4 years or less, p < 0.001; b) sharing of injection equipment: 85% anti-HCV positive intravenous drug users had shared at some time as compared to 64% seronegative subjects, p < 0.001; c) seropositivity for immunodeficiency virus infection: 25% anti-HCV positive intravenous drug users were coinfected as compared to 3.5% anti-HCV negative, p < 0.001; d) markers of ongoing (two cases) or previous hepatitis B virus infection were detected in 62% of anti-HCV positive but in 21% of anti-HCV negative cases, p < 0.01. Two initially anti-HCV negative intravenous drug users seroconverted during follow up giving an incidence rate of hepatitis C virus infection of 6.2 per 100 person-years. During the survey abnormal alanine aminotransferase levels were detected in 75% anti-HCV positive but in 24% anti-HCV negative cases (p < 0.001), with significantly higher levels in the former. These findings suggest that the circulation of hepatitis C virus among intravenous drug users has been decreasing in recent years, although new infections still occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Recombinant interferon-alfa therapy in children with chronic hepatitis C.

The efficacy of recombinant interferon-alfa therapy in children with chronic hepatitis C has been evaluated in a randomized, controlled pilot study including 27 patients, aged 2 to 14 years, without underlying systemic diseases. On entry, all patients had abnormal alanine transaminase (ALT) levels, 22 were hepatitis C virus (HCV) RNA positive, 19 had mild chronic active hepatitis, and 8 had chronic persistent hepatitis on liver biopsy. Fourteen children received 5 MU/m2 of recombinant interferon-alfa2b thrice weekly for 4 months. If at this time ALT had been reduced to at least 50% the baseline level, treatment was continued up to 12 months. The other 13 children remained untreated. The whole follow-up period lasted 24 months. Interferon was stopped at 4 months in 4 children because of an ALT increase (2 cases), unchanged ALT and febrile convulsions (1 case), and slight ALT decrease (1 case). This latter patient, however, had normal ALT at 6 months and throughout further follow-up, and cleared HCV RNA, thus behaving as a sustained responder. All 10 children treated for 12 months had normal levels of ALT, and 9 were HCV RNA negative at the end of treatment. Of the 9 children who could be followed to 24 months, 4 relapsed soon after therapy withdrawal and 5 maintained a sustained biochemical and virologic response. Overall, 6 (43%) of 14 treated children had a sustained ALT normalization associated with HCV RNA clearance as compared with only 1 (7.5%) untreated child who had a sustained ALT normalization but did not clear HCV RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

In vivo and in vitro expression of defective hepatitis B virus particles generated by spliced hepatitis B virus RNA.

The mechanisms involved in hepatitis B virus (HBV) persistence are still poorly understood. We have previously shown that the encapsidation of the singly spliced 2.2 kb-HBV RNA leads to the secretion of circulating HBV defective particles in patients with chronic hepatitis. We have now investigated the presence of the HBV defective particles in sera from patients with acute and chronic hepatitis, using polymerase chain reaction. These defective particles were detected in a larger amount in sera of patients with acute hepatitis that progressed to chronic hepatitis, or had already developed chronic hepatitis, as compared with those who recovered from acute hepatitis (the increase was estimated to be an average of 50-fold). In addition, we showed that the presence of these defective HBV particles is closely associated with the chronic course of hepatitis B virus infection and with viral multiplication. We also analyzed viral RNAs and proteins synthetized after in vitro transfection of Huh7 cell line with the corresponding defective hepatitis B virus DNA molecule. We showed that expression of the defective hepatitis B virus DNA alone leads to a marked intracellular accumulation of the major core protein (HBcAg) and to an increased secretion of hepatitis B e antigen (HBeAg). These observations may be consistent with a role of these defective hepatitis B virus (HBV) particles in viral persistence.

Base Sequence↗
PubMed1994

Purification, inhibitory properties, amino acid sequence and identification of the reactive site of a new serine proteinase inhibitor from oil-rape (Brassica napus) seed.

A new serine proteinase inhibitor, rapeseed trypsin inhibitor (RTI), has been isolated from rapeseed (Brassica napus var. oleifera) seed. The protein inhibits the catalytic activity of bovine beta-trypsin and bovine alpha-chymotrypsin with apparent dissociation constants of 3.0 x 10(-10) M and 4.1 x 10(-7) M, at pH 8.0 and 21 degrees C, respectively. The stoichiometry of both proteinase-inhibitor complexes is 1:1. The amino acid sequence of RTI consists of 60 amino acid residues, corresponding to an M(r) of about 6.7 kDa. The P1-P1' reactive site bond has been tentatively identified at position Arg20-Ile21. RTI shows no similarity to other serine proteinase inhibitors except the low molecular weight mustard trypsin inhibitor (MTI-2). RTI and MTI-2 could be members of a new class of plant serine proteinase inhibitors.

Amino Acid Sequence↗
PubMed1994

Binding of native and [homoserine lactone-52]-52,53-seco-bovine basic pancreatic trypsin inhibitor (Kunitz inhibitor) to porcine pancreatic beta-kallikrein-B and bovine alpha-chymotrypsin: thermodynamic study.

Values of the association equilibrium constant (Ka) for the binding of the native and of the cyanogen bromide-cleaved bovine basic pancreatic trypsin inhibitor (native BPTI and [Hse lactone-52]-52,53-seco-BPTI, respectively) to neuraminidase-treated porcine pancreatic beta-kallikrein-B (kallikrein) and bovine alpha-chymotrypsin (chymotrypsin) have been determined between pH 4.0 and 9.0, at 20.0 degrees C. Over the whole pH range explored, native BPTI and [Hse lactone-52]-52,53-seco-BPTI show the same affinity for kallikrein. On the other hand, the affinity of [Hse lactone-52]-52,53-seco-BPTI for chymotrypsin is higher, around neutrality, than that found for native BPTI by about one order of magnitude, converging in the acidic pH limb. The simplest mechanism accounting for the observed data implies that, on lowering the pH from 9.0 to 4.0, (i) the decrease in affinity for the binding of native BPTI to kallikrein and chymotrypsin, as well as for the association of [Hse lactone-52]-52,53-seco-BPTI to kallikrein, reflects the acidic pK shift, upon inhibitor association, of a single ionizing group; and (ii) the decrease of Ka values for [Hse lactone-52]-52,53-seco-BPTI binding to chymotrypsin appears to be modulated by the acidic pK shift, upon inhibitor association, of two non-equivalent proton-binding residues. On the basis of the stereochemistry of the serine proteinase/inhibitor contact region(s), these data indicate that long-range structural changes in [Hse lactone-52]-52,53-seco-BPTI are energetically linked to the chymotrypsin:inhibitor complex formation. This observation represents an important aspect for the mechanism of molecular recognition and regulation in BPTI.

Animals↗
PubMed1994

Interferon for chronic hepatitis C in patients cured of malignancy.

Six patients with chronic hepatitis C who were cured of malignancy were treated with recombinant interferon-alpha at the dose of 4 MU/m2 for 12 months; the post-treatment follow up period was 12 months. Therapy was stopped within 6 months in three patients because of persistently abnormal alanine aminotransferase levels. In the remaining three patients, a complete normalization of alanine aminotransferase levels was obtained during treatment but it was not maintained after the end of interferon therapy. In addition, no patient cleared hepatitis C virus ribonucleic acid in serum. These results suggest that recombinant interferon is not effective in patients with chronic hepatitis C who were cured of a previous malignancy.

Adolescent↗
PubMed1994

Patterns of antibodies to hepatitis C virus and hepatitis C virus replication in children with chronic non-A, non-B hepatitis.

Antibodies to hepatitis C virus (HCV), investigated by second- and third-generation assays, were detected in 74% of 43 children with chronic non-A, non-B hepatitis. The polymerase chain reaction identified HCV ribonucleic acid in 26 (93%) of 28 seropositive and in 1 of 10 seronegative cases. Intermittent HCV ribonucleic acid positivity, suggesting low and fluctuating viremia, was frequent in younger patients.

Adolescent↗
PubMed1994

Posttransfusion and community-acquired hepatitis C in childhood.

Following a longitudinal study of chronic non-A, non-B hepatitis in Italy and Spain, we evaluated the epidemiologic and clinical features of chronic hepatitis C in 77 consecutively observed children (35 male; mean age, 4 years) without underlying systemic diseases. All subjects were positive for antibody to hepatitis C virus in serum by second-generation tests. Forty-six patients had received blood transfusions in the perinatal period; 12 had a mother with antibodies to HCV in serum (five of these mothers were drug users or partners of a drug user); seven had a history of putative percutaneous exposure; and 12 had not been exposed to any risk factors for viral hepatitis. At presentation, only 22% were symptomatic, mean alanine-aminotransferase levels were three times the upper normal value, and liver histology showed active disease in only nine of 28 cases (32%). During a mean observation period of 6 years, only 11 of 57 patients (19%) complained of symptoms and 11 of 40 cases (27%) had histologic features of active hepatitis. Two patients had severe hepatitis with associated cirrhosis. However, only six of 57 cases (10%) achieved sustained biochemical remission. The clinical features and the outcome were similar in both the posttransfusion and the community-acquired cases. These results indicate that transfusions in the perinatal period are the single most important cause of hepatitis C in otherwise healthy children. Community-acquired cases represent an heterogeneous epidemiologic group in which maternal transmission, whether perinatal or postnatal, could be relevant.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1994

Recombinant interferon-alpha 2a hastens the rate of HBeAg clearance in children with chronic hepatitis B.

We conducted a prospective controlled study of the efficacy of recombinant interferon-alpha 2a in 77 children (44 boys, 33 girls, mean age 8 yr) with chronic hepatitis B. All patients had seropositive results for HBeAg and hepatitis B virus DNA; 52 had chronic persistent or nonspecific reactive hepatitis, and 25 had mild active hepatitis. Twenty-one children (group 1) received recombinant interferon-alpha 2a 7.5 megaunits/m2 three times weekly for 6 mo, 19 children (group 2) received megaunits/m2 on the same schedule and 37 (group 3) remained untreated. At 6 mo, HBe antigen-to-antibody seroconversion associated with biochemical remission was seen in 24% of patients in group 1, 5% in group 2 and 3% in group 3 (p < 0.05 vs. group 1). At 18 mo, seroconversion rates were 30% in group 1, 21% in group 2 and 13.5% in group 3. These results suggest that a course of recombinant interferon-alpha 2a accelerates HBeAg-HBe antibody seroconversion in children. High baseline ALT levels were sensitive predictors of seroconversion in both treated and untreated patients. In contrast, baseline IgM HBc antibody levels influenced the rate of anti-HBe seroconversion only in untreated patients. These findings suggest that, in children as well as in adults, recombinant interferon-alpha 2a favors the clearance of hepatitis B virus replication, enhancing the host antiviral immunoresponse.

Adolescent↗
PubMed1993

Selection of a precore mutant of hepatitis B virus and reactivation of chronic hepatitis B acquired in childhood.

A 14-year-old girl with chronic hepatitis B had seroconversion from hepatitis B e antigen to antibody and achieved biochemical remission after 2 years. The disease reactivated 9 years later when a precore mutant had become the prevalent hepatitis B virus strain in serum. These results suggest that selection of a precore mutant might induce reactivation during adult life of chronic hepatitis B acquired in childhood, thus worsening the prognosis.

Adolescent↗
PubMed1993

Long-term evolution of chronic delta hepatitis in children.

Twenty-three children, aged 3 to 15 years, with chronic delta hepatitis have been followed for 5 to 12 years to evaluate long-term outcome. Although 83% of patients had chronic active hepatitis when first seen, with cirrhosis in 26%, the clinical and biochemical features of the disease remained reasonably stable during observation; liver histologic findings, obtained in 14 patients, worsened in only two.

Adolescent↗
PubMed1993

Prenatal development of glucocorticoid receptor gene expression and immunoreactivity in the rat brain and pituitary gland: a combined in situ hybridization and immunocytochemical analysis.

By means of in situ hybridization and immunocytochemical techniques it has been possible to follow the prenatal development of glucocorticoid receptor (GR) messenger RNA (mRNA) expression and GR immunoreactivity (IR) in the rat brain from embryonic day (E) 15 to 22. A 700-base-pair GR cDNA fragment was used for RNA probe generation. In the immunocytochemical analysis a mouse monoclonal antibody (IgG2a) against the rat liver GR was used in combination with the indirect fluorescence technique or the avidin-biotin immunoperoxidase method. At E15 till E22 a moderate to strong GR mRNA signal was observed within the neuro-epithelium from the medulla oblongata to the telencephalon. A moderate to strong labelling was also present within the paraventricular hypothalamic nucleus, the arcuate nucleus, the nucleus raphe magnus, the nucleus raphe obscurus and the locus coeruleus. In these areas a weak to moderate nuclear GR IR developed in nerve cells 1 or 2 days after the appearance of the GR mRNA signal. From E15 the adenohypophysis showed the strongest expression of GR mRNA. At E17 a strong GR IR was especially demonstrated in the nuclei of many pituitary cells, some exhibiting adrenocorticotropin IR. The results open up the possibility that there exist active GR in embryonic life capable of regulating proliferation events within the adenohypophysis and the neuro-epithelia of the brain. This embryonic GR may modulate the development of inter alia neuro-endocrine areas such as the paraventricular and arcuate nuclei and arousal-related areas such as the central 5-hydroxytryptamine and noradrenaline neuronal systems. Provided that this embryonic GR is capable of becoming activated by glucocorticoids in fetal life, it may mediate several neurochemical and behavioural impairments caused by prenatal stress.

Animals↗
PubMed1993

Hepatitis C in childhood: epidemiological and clinical aspects.

Hepatitis C virus (HCV) is responsible for most cases of chronic non-A, non-B hepatitis in multi-transfused children, but has been also implicated in at least one third of cases without history of parenteral exposure. We have recently evaluated the natural history of chronic hepatitis C in 37 children without underlying systemic diseases. None of the patients had a history of acute hepatitis and only 22 were symptomatic at presentation. Liver histology was consistent with active liver disease of mild to moderate activity in 42% of cases (one child had cirrhosis) and with persistent or lobular hepatitis in the remaining cases. During a mean follow-up period of 3.4 +/- 3.2 years symptoms were rarely observed and none of the patients developed liver failure, but 97% maintained abnormal alanine-aminotransferase levels. These results suggest that chronic hepatitis C in children, at least in its early stage, is a mild disease infrequently associated with severe liver lesions; however the persistence of liver damage over the years raises questions about the long-term outcome of the illness and about the rationale of antiviral therapy.

Acute Disease↗