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Biomedical subjects

F Bortolotti

Publications and source records attributed to F Bortolotti.

At least 55 records · Page 3Linked to original sources
PubMed1998

Changing epidemiologic pattern of chronic hepatitis C virus infection in Italian children.

OBJECTIVE: To evaluate the epidemiologic features of chronic hepatitis C virus (HCV) infection in children. STUDY DESIGN: All 106 children with chronic HCV infection consecutively observed in 3 Italian pediatric centers between 1991 and 1997 entered the study. RESULTS: Fifteen children had a history of non-A, non-B hepatitis, and 5 complained of nonspecific symptoms. The 86 remaining patients were free of symptoms and were recruited after HCV screening for intercurrent diseases, maternal infection, or other putative exposure; 39% (none of 30 children born after 1990) had received transfusions, whereas 44%, had a mother with HCV infection. Of the 47 infected mothers, 36% were or had been intravenous drug users, 15% had received transfusions, and 45% had no history of exposure. CONCLUSIONS: Children with chronic HCV infection are often free of symptoms, and thus HCV screening for putative risk has greatly increased the chances of diagnosis. Vertical transmission seems to now be the most common route of infection. Both current and past maternal intravenous drug abuse are risk factors for pediatric infection; however, in an area with relatively high prevalence of anti-HCV in the general population such as Italy, a consistent proportion of infectious mothers have no risk factors of HCV exposure.

Adolescent↗
PubMed1998

Outcome of chronic hepatitis B in Caucasian children during a 20-year observation period.

BACKGROUND/AIMS: Chronic hepatitis B virus infection can lead to cirrhosis and hepatocellular carcinoma, particularly in men over 40 years of age and in areas where childhood-onset infection is common. The sequence of events from paediatric infection to severe disease in adults is only partially known. The aim of this study was to evaluate the evolution of chronic hepatitis B acquired in childhood during 20 years of follow-up. PATIENTS: One hundred and eighty-five consecutive, otherwise healthy, Caucasian children were enrolled in Padua (Italy) and in Madrid (Spain) between 1975 and 1985, and followed for an average period of 13 years; 168 were hepatitis B e antigen (HBeAg) positive and five had cirrhosis. RESULTS: Thirty patients received steroids or levamisole and 21 interferon, but treatment did not significantly influence HBeAg clearance. Overall, two (1.1%) children, with initial cirrhosis, developed hepatocellular carcinoma and the other three (1.6%) cirrhotic patients became asymptomatic carriers of infection after anti-HBe seroconversion and biochemical remission; 14 (7.5%) children maintained HBeAg positive hepatitis; 155 (83.8%) became asymptomatic carriers of infection after anti-HBe seroconversion and biochemical remission; six (3.2%) experienced reactivation of liver disease and viral replication after remission and five (2.7%) maintained biochemical features of liver damage after HBeAg clearance. Only 6% cleared hepatitis B surface antigen. CONCLUSIONS: Even considering the bias of treatment, the large majority of Caucasian children with chronic hepatitis B became asymptomatic carriers of infection with normal alanine amino-transferase during the first 20 years of observation. Cirrhosis is an early, rare complication, and a risk factor for hepatocellular carcinoma. A subgroup of patients who experienced reactivation or maintained liver damage after HBeAg clearance seems to be at greater risk for disease progression during adult life.

Adjuvants, Immunologic↗
PubMed1998

Plasma prolactin response to D-fenfluramine is blunted in bulimic patients with frequent binge episodes.

BACKGROUND: Abnormalities of brain serotonin (5-HT) transmission have been implicated in the pathophysiology of bulimia nervosa (BN), but no conclusive data have yet been provided. The purpose of this study was to assess 5-HT transmission via the measurement of the prolactin (PRL) response to the specific 5-HT releasing agent D-fenfluramine (D-FEN) in both patients with BN and comparison subjects. METHODS: According to a double-blind placebo-controlled design, plasma PRL response to D-FEN was measured in 14 drug-free bulimics and 14 matched healthy controls. In both patients and controls, eating-related psychopathology, depressive and obsessive-compulsive symptoms, and aggressiveness were measured by rating scales. RESULTS: Baseline plasma levels of PRL and 17 beta-oestradiol were significantly reduced in bulimic patients, whereas basal plasma levels of cortisol did not significantly differ from healthy controls. PRL response to D-FEN was not different between patients and controls as groups, but it was significantly blunted in bulimics with high frequency bingeing (> or = 2 binge episodes per day; N = 7) as compared to both those with low frequency bingeing (< or = 1 binge episode per day; N = 7) and matched controls. A significant negative correlation emerged between the frequency of binge episodes and the hormone response to D-FEN. Moreover, although patients scored higher than healthy subjects on rating scales assessing depressive and obsessive-compulsive symptoms and aggressiveness, no significant correlation was found between these measures and the PRL response to D-FEN. CONCLUSIONS: These results support the idea that serotonin transmission is impaired in bulimic patients with frequent binge episodes.

Adult↗
PubMed1998

Enzymatic synthesis of 2'-O-acyl prodrugs of 1-(beta-D-arabinofuranosyl)-5(E)-(2-bromovinyl)uracil and of 2'-O-acyl-araU, -araC and -araA.

Pig liver esterase (EC 3.1.1.1) catalysed regioselective hydrolysis of 1-(2,3,5-tri-O-acyl-beta-D-arabinofuranosyl)uracil, -cytosine and -adenine to give the corresponding 2'-monoesters effectively and in high yield. This methodology enabled the preparation of 1-(2-O-acyl-beta-D-arabinofuranosyl)-5-[(E)-(2-bromovinyl)]uracil prodrugs which, although slightly less active than the parent 1-(beta-D-arabinofuranosyl)-5-(E)-(2 bromovinyl)uracil (sorivudine; BV-araU), were strongly active in vitro against varicella-zoster virus (ED50 2.4-45 ng/ml). The retarded rates of enzymatic hydrolysis of the 2'-esters imply that they might function as lipophilic prodrugs, leading to increased plasma and cellular concentrations. In view of the marked in vitro activity, they represent an interesting approach to arabinofuranosyl nucleoside prodrugs with improved pharmacokinetics and enzymatic stability.

Animals↗
PubMed1998

Prolactin response to d-fenfluramine is blunted in people with anorexia nervosa.

BACKGROUND: Several studies have explored serotonin (5-HT) transmission in people with anorexia nervosa, but their results have been inconsistent. METHOD: According to a double-blind placebo-controlled design, plasma prolactin response to the specific serotonergic probed d-fenfluramine was investigated in 10 under weight and two normal-weight women with anorexia, and in 12 age-matched healthy females. Eating-related psychopathology, depressive and obsessive--compulsive symptoms, and aggressiveness were measured by appropriate rating scales. RESULTS: Compared with healthy control subjects, the women with anorexia showed reduced baseline prolactin and oestrogen levels and increased basal cortisol concentrations. The prolactin response to d-fenfluramine was blunted and did not correlate with psychopathological measures. CONCLUSIONS: These results support a dysfunction of 5-HT transmission in anorexia nervosa. This dysfunction does not seem to be related to concomitant depressive or obsessive--compulsive symptoms or to the level of aggressiveness of the patients.

Adolescent↗
PubMed1998

Structure-activity relationships of HIV-1 protease inhibitors containing gem-diaminoserine core unit.

Two series of peptidomimetics containing 1,1-diamino-2-hydroxyethane (gSer) core structure were prepared, from amino acid starting materials, and evaluated as inhibitors of HIV-1 protease (HIV-1 Pr). Asymmetrical pseudodipeptides, Y-Xaa-gSer-Y (Y = Z, Fmoc; Xaa = Cha, Phe, Tyr, Tic) showed weak inhibitory potency (IC50 > or = 5 mumol/l), whereas the corresponding pseudotripeptides displayed a more significant HIV-1 Pr inhibition: Fmoc-Tic-gSer-Tic-Fmoc (Fmoc = fluorenylmethyloxycarbonyl, Tic = 1,2,3,4-tetradroisoquinoline-3-carboxylic acid) was the most potent compound of the series (IC50 = 385 nmol/l).

Chemical Phenomena↗
PubMed1997

Plasma prolactin response to d-fenfluramine in obsessive-compulsive patients before and after fluvoxamine treatment.

The prolactin (PRL) responses to oral d-fenfluramine (30 mg) and placebo were assessed in 13 patients with obsessive-compulsive disorder (OCD) and in matched healthy subjects. After the neuroendocrine test, all patients were treated with fluvoxamine maleate (150-300 mg/day). At the end of the 10th week of treatment, 10 patients underwent again the neuroendocrine assessment. In drug-free patients, the PRL response to d-fenfluramine was significantly lower than in the comparison group. After 10-week fluvoxamine treatment, the PRL response to the serotonergic agent normalized. These findings suggest that, at least at the neuroendocrine level, central serotonergic responsivity is reduced in drug-free OCD patients, and that long-term fluvoxamine administration is associated with its normalization.

Adolescent↗
PubMed1997

Effect of chronic clozapine administration on [3H]MK801-binding sites in the rat brain: a side-preference action in cortical areas.

We studied modifications in [3H]MK801-binding sites in the rat brain after chronic clozapine. We found a 20-30% reduction of [3H]MK801-binding sites in the anterior cingulate, frontoparietal motor and frontoparietal somatosensory cortices on the left side but none on the right. We also demonstrated a 20% bilateral increase of N-methyl-D-aspartate (NMDA) receptors in the dentate gyrus of the hippocampus. No changes were found in the prefrontal cortex, caudate-putamen, nucleus accumbens, hippocampus or olfactory tubercle.

Animals↗
PubMed1997

Hepatitis G and C virus coinfection in children.

Infection with the hepatitis G virus (HGV), as indicated by the presence of HGV ribonucleic acid, was sought in 57 children with chronic hepatitis C virus infection. HGV infection was found in 2 children (3.5%), or 14% of the babies whose mothers were former drug abusers. Maternal drug abuse is an important risk factor for hepatitis G and C virus coinfection in children in our area.

Adolescent↗
PubMed1997

Hepatitis C virus infection and related liver disease in children of mothers with antibodies to the virus.

OBJECTIVE: To evaluate the clinical, biochemical, and virologic features associated with hepatitis C virus (HCV) infection acquired early in life from mothers with antibodies to HCV (anti-HCV). STUDY DESIGN: Multicenter prospective-retrospective study in Italian children. PATIENTS: Two groups of children were investigated. Group 1 included 14 infants, born to mothers with anti-HCV but without human immunodeficiency virus infection, who became seropositive for HCV RNA during the first year of life and were thus considered infected. Group 2 included 16 children with chronic hepatitis C, aged 1 1/2 to 14 years, whose mothers were the unique potential source of infection. Both groups were followed for 12 to 48 months. METHODS: Alanine transaminase (ALT), anti-HCV, and HCV RNA were investigated by the polymerase chain reaction on entry to the study and during follow-up. RESULTS: All children in group 1 had anti-HCV throughout follow-up, and all had ALT abnormalities, ranging from 1.5 to 10.5 times the normal value during the first 12 months. During further follow-up, 5 of 10 children had HCV RNA with abnormal ALT values, 3 had a return to normal of the ALT values but continued to have viremia, and 2 eventually had normal ALT values and clearance of HCV RNA. Of the 16 children in group 2, all were free of symptoms and 62% had only slight ALT elevations; 7 who underwent liver biopsy had histologic features of minimal or moderate hepatitis. CONCLUSIONS: HCV infection acquired early in life from mothers with anti-HCV is usually associated with biochemical features of liver damage during the first 12 months of life. Progression to chronicity seems to occur in the majority of cases, although HCV-associated liver disease is likely to be mild throughout infancy and childhood.

Alanine Transaminase↗
PubMed1997

Detection of different viral strains of hepatitis B virus in chronically infected children after seroconversion from HBsAg to anti-HBs indicating viral persistence.

BACKGROUND/AIMS: Seroconversion to anti-HBs or the loss of HBsAg is usually associated with complete elimination of the replicative hepatitis B virus. Usually in these patients hepatitis B virus DNA (HBV DNA) becomes undetectable. Routine controls of patients who underwent anti-HBs seroconversion by more sensitive tests showed that in some cases the virus persisted in the patient. Therefore the aim of our study was to evaluate if virus persistence could also be found in children with chronic hepatitis B after anti-HBs seroconversion. The virus pool should be characterized before and after seroconversion. METHODS: Viral DNA was extracted from nine HBsAg negative or anti-HBs positive sera of children, previously diagnosed as chronic HBsAg carriers. HBV DNA was amplified by polymerase chain reaction. Subsequently the nucleotide sequences of the polymerase chain reaction product in the a-determinant region (aa 121-161) were analyzed on an automatic fluorescent sequencer. RESULTS: In the sera of seven children, HBV DNA was detected in the HBsAg negative phase of the HBV infection. Mutations in codons 122, 125, 127, 131, 134, 143, 159 and 161 of the S gene could be documented, resulting in amino acid changes. In three patients the sequence analysis revealed changes in the HBV genotype from genotype A (serotype adw) to genotype D (serotype ayw) during seroconversion to anti-HBs. CONCLUSIONS: These data demonstrate that persistence of the hepatitis B virus can also occur in HBsAg negative and anti-HBs positive children. After loss of HBsAg, no specific HBV variant was identified. Although a conclusive explanation for the selection process cannot be provided, it remains a fact that the 'surviving' viral strain was mostly represented by genotype D.

Amino Acid Sequence↗
PubMed1997

Differences between morning and afternoon hormonal responses to D-fenfluramine in healthy humans.

The prolactin (PRL) and cortisol responses to oral D-fenfluramine (30 mg) and placebo were measured in seven healthy subjects (two women and five men) in the morning and in the afternoon. As compared to placebo, D-fenfluramine significantly increased plasma PRL levels in both the morning and the afternoon, with no significant circadian difference. On the contrary, D-fenfluramine significantly enhanced plasma cortisol levels in the afternoon, but not in the morning. These data suggest that the time of the day at which the D-fenfluramine challenge test is carried out may be an important variable in determining the glucocorticoid response to the 5-HT releasing agent in humans.

Adult↗
PubMed1997

HIV-1 protease inhibitors containing a novel C2 symmetrical hydroxyalkylgem-diamino core structure.

Two series of peptidomimetics containing a novel C2 symmetrical hydroxyalkylgem-diamino core structure were prepared, from amino acid starting materials, and evaluated as inhibitors of HIV-1 protease (HIV-1 Pr). 1,1-Diamino-3-hydroxypropane (gHse) derivatives showed weak inhibitory potency (IC50 > 10 microM). In the 1,1-diamino-2-hydroxyethane (gSer) series, a compound containing P1/P1' benzyl and P2/P2'Fmoc substituents, displayed a significant HIV-1 Pr inhibition (IC50 = 440 nM).

Amino Acid Sequence↗
PubMed1996

Lymphoblastoid interferon alfa with or without steroid pretreatment in children with chronic hepatitis B: a multicenter controlled trial.

The comparative efficacy of prednisolone followed by interferon alfa (IFN-alpha) versus IFN-alpha alone in enhancing the rate of antibody to hepatitis B e antigen (anti-HBe) seroconversion has not been evaluated in a large cohort of white children. To determine this, a multicenter-controlled trial was conducted in 95 hepatitis B virus (HBV)-DNA/hepatitis B e antigen (HBeAg)-positive children (median age, 9 years [range, 2-16 years]; 56 boys; 84 [89 percent] white), all having inflammatory changes on liver biopsy. Patients were randomized to receive either prednisolone followed by IFN-alpha (n = 34); placebo followed by IFN-alpha (n = 30); or no treatment (n = 31). The prednisolone/placebo was given on a double-blind basis. Lymphoblastoid IFN-alpha was given at 5 MU/m(2) three times a week for 12 weeks. Baseline clinical, biochemical, and histological features were similar for the three groups. The majority (85 percent) had a baseline aspartate aminotransferase (AST) level < or = 100 IU/L. On follow-up between 12 and 18 months (median, 15 months) after treatment, the loss of HBeAg with anti-HBe seroconversion was more common in patients pretreated with steroids (12 of 34 [35 percent]) or placebo [12 of 30 (40 percent)] as against controls (4 of 31 [13 percent], P< .05). Factors predictive of anti-HBe seroconversion were baseline HBV-DNA concentration of < or = 1,000 pg/mL and a greater degree of portal tract inflammation on pretrial biopsy. Our results show that in white children treatment with IFN-alpha, at the dose and duration used in this study, improves the rate of anti-HBe seroconversion. Steroid priming does not potentiate the effect of IFN-alpha.

Adolescent↗
PubMed1996

Autoantibody prevalence in chronic hepatitis B virus infection: effect in interferon alfa.

The most effective treatment of chronic hepatitis B virus (HBV) infection is interferon alfa (IFN-alpha), a potentially severe side effect of which is the induction of autoimmunity. To assess whether IFN-alpha causes clinical or serological autoimmune manifestations, we studied 61 children randomized to receive 5 MU/m2 of IFN-alpha three times per week for 12 weeks, with or without steroid priming or no treatment. Autoantibodies to antinuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC), liver kidney microsomal type 1, mitochondrial, liver cytosolic antigen, thyroid microsomal, and thyroid globulin were detected by standard techniques. Over a median of 4 years (range, 1-5 years) from randomization, no clinical signs of autoimmunity were observed. Autoantibody positivity for nuclei, smooth muscle, and/or gastric parietal cells was observed on at least one occasion in 42 of 61 children (69%), with no overall difference in the prevalence between patients treated with interferon alone (19 of 24 [79%]), steroids plus interferon (13 of 20 [65%]), or untreated controls (10 of 17 [59%]). There was also no difference in the autoantibody prevalence before, during, and at follow-up after cessation of treatment in both interferon-treated and interferon-untreated patients. Autoantibodies are common in chronic HBV infection, and their prevalence is uninfluenced by IFN-alpha.

Adolescent↗
PubMed1996

Non-organ specific autoantibodies in children with chronic hepatitis C.

BACKGROUND/AIMS: Recent studies in adult patients have established a relationship between hepatitis C virus infection and the presence of liver-kidney microsomal autoantibody type 1 (LKM1). Conversely, little is known regarding the relationship between hepatitis C and autoimmunity in children. In this study, we investigated non-organ specific autoantibodies in 40 otherwise healthy Italian children with chronic hepatitis C. METHODS: All but four patients included in the study were asymptomatic. Liver histology, obtained in 35, showed features ranging from minimal to mild chronic hepatitis. Autoantibodies were investigated by indirect immunofluorescence. HCV RNA was assayed by the polymerase chain reaction in 34 cases and viral genotypes were determined. RESULTS: Antinuclear antibodies were detected in three (7.5%) cases, one with a homogeneous pattern; smooth muscle autoantibodies in seven (17.5%) cases, always with V (vessels only) specificity and LKM1 in four (10%), at titers ranging from 1:20 and 1:2560. Clinical and virologic features did not significantly differ between autoantibody positive and negative cases, although infections with HCV genotypes 1a and 2 were more frequent in LKM1-positive patients. During observation, the child with the highest LKM1 titre was unsuccessfully treated with alpha interferon but responded to steroids. Twelve LKM1 negative children were also treated with interferon and one developed low LKM1 titers concomitant with an alanine aminotransferase flare. The sera of the five LKM1-positive children with investigated by immunoblotting with a human microsomal fraction and peptide 257-269 of cytochrome P450IID6. Only the serum of the child with the highest LKM1 titers was reactive. CONCLUSIONS: These results show that a consistent proportion of children with chronic hepatitis C circulate non-organ specific autoantibodies. The prevalence of LKM1 is greater than in adults and this could raise problems for the treatment of the disease with interferon. The analysis of LKM1 target antigens might help to identify putative cases of "true" autoimmune hepatitis with concomitant HCV infection that could benefit from steroid treatment.

Adolescent↗
PubMed1996

Chronic viral hepatitis in childhood.

In endemic areas infection with hepatitis B virus is a common cause of chronic liver disease in childhood. High levels of viral replication and mild ALT abnormalities are the rule in children infected perinatally and many of them are likely to maintain viral replication through their youth. Conversely about 90% of children infected later in life clear HBeAg and achieve sustained remission of liver disease before reaching adulthood. The eventual outcome of infection and disease in these patients remains unpredictable as reactivation of liver damage and viral replication may occur after several years of sustained remission. Cirrhosis is a rare and early complication of chronic HBV infection in children, and a risk factor for hepatocellular carcinoma. IFN therapy can accelerate HBV DNA clearance, improving the spontaneous anti-HBe seroconversion rate in Caucasian children by two to three times. Hepatitis delta is the most severe form of chronic viral hepatitis in childhood. Cirrhosis can be diagnosed in up to 26% of patients at presentation, and few cases respond to IFN therapy. Hepatitis C is relatively rare in children. Before the discovery of HCV, blood transfusions were the most common source of infection. Hepatitis C is usually a mild, asymptomatic disease in otherwise healthy children, but has a poor propensity to spontaneous remission over the years. For this reason, and based on the experience in adults, IFN treatment is now being evaluated.

Child↗