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Biomedical subjects

C Scolastico

Publications and source records attributed to C Scolastico.

At least 19 recordsLinked to original sources

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↗

Influence of chronic coinfection with hepatitis B and C virus on liver histology.

BACKGROUND: Few data are available on histological features of chronic hepatitis B (HBV) and C (HCV) virus coinfection. PATIENTS AND METHODS: We enrolled 142 consecutive patients with viral chronic hepatitis on their first liver biopsy: 27 HBsAg and anti-HCV positive (case BC group), 57 HBsAg positive and anti-HCV negative (control B group) and 58 anti-HCV positive, HBsAg/anti-HBs/anti-HBc negative (control C group). RESULTS: Patients in the case BC group showed serum HBVDNA (37% vs 71.9%, p < 0.005) and ground-glass hepatocytes (37% vs 66.7%, p < 0.01) less frequently than those in the control B group. The case BC group showed a lower prevalence of patients with detectable HCV-RNA than the control C group (60% vs 92.3%, p < 0.001) and a significantly higher fibrosis score (2.1 +/- 1.2 vs 1.5 +/- 1.1, p < 0.05). Of the 27 patients in the case BC group, 10 lacked serum HCV-RNA and showed significantly higher histological activity index (HAI) and fibrosis scores than those found in the 17 HCV-RNA positive (8.5 +/- 4.4 vs 5.4 +/- 2.4 for HAI, p < 0.05; 3.0 +/- 1.3 vs 1.69 +/- 1.0, p < 0.05 for fibrosis). CONCLUSION: Liver histology seems to be more severe in chronic coinfection with HBV and HCV than in single infection, particularly when HCV replication is impaired.

Adult↗

Prevalence of genotypic resistance to nucleoside analogues and protease inhibitors in antiretroviral-naive HIV patients in Campania, Italy.

The aim of our study was to determine the prevalence of genotypic resistance to nucleoside analogues and protease inhibitors before and after 1997, the year of introduction of Highly Active Antiretroviral Therapy (HAART) in Campania (Italy). Forty-eight plasma HIV-RNA positive patients who had not been previously treated for HIV infection (naïve) were enrolled in two Divisions of Infectious Diseases. The main demographic characteristics were collected for each subject and the primary mutant genotypes were sought only in HIV-RNA positive patients with viral loads higher than 10,000 copies/ml. The diagnosis of HIV infection dated back to before 1996 for 21 out of 48 patients and to after 2000 for the other 27. INNO-Line Probe Assay (LiPA) HIV-RT and INNO-LiPA HIV protease (Innogenetics, Italy) were used to detect mutations conferring resistance to zidovudine, didanosine, zalcitabine, lamivudine, stavudine, saquinavir, indinavir, rotonavir, nelfinavir and amprenavir. No mutations associated with primary resistance to nucleoside analogues and protease inhibitors were detected in the 21 patients who had acquired HIV infection before 1996, whereas one or more mutations were seen in three of the 27 (11.1%) patients with HIV infection diagnosed after 2000. This study confirms that LiPA is a suitable tool for epidemiological surveys of HIV genotypic primary resistance. Drug-resistant HIV-1 genotypes, resistant both to nucleoside analogues and protease inhibitors, were detected only in subjects who had acquired HIV infection after 2000, most of whom had zidovudine-resistant mutants. These data suggest that the introduction of HAART has brought about the circulation of drug-resistant HIV genotypes.

Adult↗

Potent integrin antagonists from a small library of RGD-including cyclic pseudopeptides.

[structure: see text]. A small library of cyclic RGD pseudopentapeptides incorporating stereoisomeric 6,5- and 7,5-fused bicyclic lactams was synthesized with the aim of developing active and selective integrin antagonists. The solid-phase synthesis and activity of these RGD derivatives is described. The approach led to two of the most active known inhibitors of alpha(V)beta3 receptor.

Antineoplastic Agents↗

HCV genotype and "silent" HBV coinfection: two main risk factors for a more severe liver disease.

To evaluate whether HCV genotype and a "silent" HBV infection may be related to a more severe clinical presentation of liver disease, 205 anti-HCV/HCV-RNA positive, HBsAg/anti-HBs negative patients with chronic hepatitis (113 males and 92 females; median age 55 years, range 18-77), were studied on presentation at the Liver Unit from January 1993 to December 1997. Presence of serum anti-HBc, in the absence of HBsAg and anti-HBs, was considered a marker of "silent" HBV infection. Of the 205 patients, 134 had undergone percutaneous liver biopsy. Two main diagnosis groups were established: the mild liver disease group (76 patients), and the severe liver disease group (109 patients); 20 patients who had refused to undergo liver biopsy were not included in the clinical and virological evaluation because the diagnosis was uncertain. The prevalence of severe liver disease was similar in the genotype 1 and non-1 groups (61.3% of 98 patients with genotype 1 and 52.9% of 70 patients with a non-1 genotype). Instead, the 88 patients with "silent" HBV infection showed a higher percentage of severe liver disease than the 97 anti-HBc negative patients (72.7% vs. 46.4%, respectively: P < 0.0005). Of the 88 anti-HBc positive patients, the prevalence of those with severe liver disease was similar in the 32 cases with serum HBV-DNA as detected by PCR and in the 56 HBV-DNA negative (81.2% vs. 67.8%, P = 0.4). The relation between "silent" HBV infection and severe liver disease was observed both in genotype 1 and non-1 infected patients. Nevertheless, the anti-HBc negative patients infected by genotype 1 showed a severe liver disease more frequently than those infected by a non-1 genotype, with a difference that is significant to the statistical analysis (P < 0.05). The findings suggest that "silent" HBV infection in anti-HCV positive chronic hepatitis enhances the severity of the liver disease. Evidence was also found that in patients without "silent" HBV infection there is a correlation between the presence of HCV genotype 1 and the severity of liver disease.

Adolescent↗

Isolated anti-HBc in chronic hepatitis C predicts a poor response to interferon treatment.

The sustained response to interferon-alpha treatment was evaluated in 147 anti-HCV/HCV-RNA-positive, HBsAg-negative, chronic hepatitis patients, according to HCV genotypes and the presence or absence of anti-HBs and anti-HBc. These patients had been included in a controlled study on the safety, tolerability, and efficacy of three types of interferon-alpha given at a dose of 3 MU three times weekly for 52 weeks. One hundred and two patients had HCV genotype 1, 42 a non-1 HCV genotype and 3 multiple HCV genotypes; 46 were anti-HBs and anti-HBc negative (group A), 50 anti-HBs and anti-HBc positive (group B), and 51 anti-HBs negative and anti-HBc positive ("isolated" anti-HBc, group C). Serum HBV-DNA was detected by polymerase chain reaction in 15 of the 51 (29.4%) patients in group C and in none of those in groups A or B. The Sustained Response rate was higher in patients with a non-1 HCV genotype than those with HCV genotype 1 (31% vs. 17.7%, P > 0.1). Fewer patients in group C showed a sustained response than in group A or group B (7.8% vs. 30.4%, P = 0.009 and 7.8% vs 28%, P = 0.017, respectively). Moreover, the sustained response rate was high in patients with a non-1 genotype, both in group A (42.8%) and in group B (42.8%), intermediate in patients with HCV genotype 1 (23.3% in group A and 22.2% in group B) and low in group C, irrespective of HCV genotype (8.3% for genotype 1 and 7.1% for other genotypes). The data indicate that patients with HCV chronic hepatitis and isolated anti-HBc show a poor response to IFN-alpha, irrespective of the HCV genotype.

Adolescent↗

Antibodies to hepatitis A virus in Italian patients with chronic liver disease.

To improve our knowledge for future hepatitis A virus (HAV) vaccination strategies we carried out a multicentre study on naturally acquired immunological protection against HAV in patients with chronic hepatitis in Italy. We enrolled 830 consecutive patients with chronic hepatitis on their first observation at one of the six Italian liver units participating in the study. Six hundred and fifty-eight patients (79.3%) were positive for total anti-HAV and 172 (20.7%) were negative. The anti-HAV negative patients were younger (median age 33, range 11-78) than the anti-HAV positive (median age 56, 18-87). There was a higher prevalence of cases with circulating anti-HAV among the 508 patients residing in southern Italy than in the 322 residing in northern Italy (88.8% vs. 64%, P < 0.001). No significant difference in the anti-HAV prevalence was observed between patients from northern Italy and those from southern Italy aged 0-30 years or in those over 60 years, while in those 31-60 years old there was a higher prevalence of anti-HAV positive patients from southern Italy (90.2% vs. 65.8%, P < 0.0001). Of the patients with liver cirrhosis in this study, only 3 of the 26 (11.5%) from northern Italy and 8 of the 228 (3.5%) from southern Italy had no immunological protection against HAV infection. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV is substantial in Italy, particularly in the north of the country, and that new vaccination strategies are needed.

Adolescent↗

Does HIV infection favor the sexual transmission of hepatitis C?

BACKGROUND: There are widely discrepant findings on the sexual transmission of hepatitis C virus (HCV), commonly transmitted by the parenteral route. Coinfection with HCV is common in subjects infected with HIV. GOAL: This case-control study evaluated the prevalence of anti-HCV in subjects with hetero- or homosexual contact and no history of intravenous drug abuse or blood transfusion, according to the presence or absence of HIV infection. STUDY DESIGN: In this case-control study, the cases considered were 106 consecutive patients who showed positive anti-HIV test results. For each case, two control subjects were selected who had been screened for HIV infection at the authors' center and found to have anti-HIV-negative test results, and who matched the case in terms age (+/- 5 years), gender, and risk factor for parenterally transmitted infections. RESULTS: The prevalence of subjects with positive test results for hepatitis B surface antigen (HBsAg) was similar between cases and control subjects (4.7% versus 2.4%). Positivity for anti-hepatitis B core antigen in connection with negative test results for HBsAg was observed more frequently in the 106 cases than in the 212 control subjects (33.9% versus 15.6%; P = 0.0003). Anti-HCV positivity was more frequent in the cases than in the control subjects (15.1% versus 5.2%; P = 0.005). In particular, among subjects who had hetero- or homosexual intercourse with a steady partner who had positive anti-HIV test results, anti-HCV positivity was observed in 18.7% of the 32 cases and 1.6% of the 64 control subjects (P = 0.008). CONCLUSION: This study demonstrated that in subjects who had only a sexual risk factor for parenterally transmitted infections, HIV may enhance the sexual transmission of HCV.

Adolescent↗

Can HCV affect the efficacy of anti-HIV treatment?

To evaluate the impact of new antiretroviral combinations (HAART: Highly Active Anti Retroviral Therapy) on HCV replication and liver enzyme levels, we analysed the changes in HCV viremia and aminotransferase levels in HIV and HCV co-infected patients. Moreover, to evaluate the influence of HCV infection on the efficacy of HAART, we compared the virological, immunological and biochemical response to antiretroviral combinations in anti-HIV positive subjects with or without HCV infection. We enrolled eight consecutive outpatients with HIV-HCV coinfection and with indications for HAART (Group A). For each patient in group A, we selected an anti-HIV negative patient with indications for HAART, pair-matched for age, sex, risk factor for HIV infection, presumed duration of infection, number of CD4 cells, HIV viremia and treatment schedule (Group B). A statistically significant increase in CD4 in both groups was found at 1st, 3rd and 6th month of antiretroviral therapy. A decrease in HIV-RNA in both groups was observed at 1st and 6th month of treatment. The percentage of patients with undetectable HIV-RNA at the 1st month was higher in Group B than in Group A (8/8 vs. 3/8, p = 0.025). Basal HCV-RNA viremia was very high in each case and no variations during treatment were observed. During therapy the aminotransferase levels slightly decreased in Group A and consistently increased in Group B. In Group A the differences were not significant to the statistical analysis; in Group B the aminotransferase levels at 3rd and 6th month were significantly higher than those observed at the baseline.

Adult↗

Virologic and clinical expressions of reciprocal inhibitory effect of hepatitis B, C, and delta viruses in patients with chronic hepatitis.

We studied 648 hepatitis B surface antigen (HBsAg)- and/or anti-hepatitis C virus (HCV)-positive patients to evaluate the virologic and clinical characteristics of multiple hepatitis viral infection. We defined as Case B-C an HBsAg/anti-HCV positive patient and as Case b-C an anti-HCV/anti-HBc-positive, HBsAg/anti-HBs-negative patient. For each Case B-C we scheduled as Control-B an HBsAg positive and anti-HCV negative patient and as Control-C an HBsAg/anti-HBs/anti-hepatitis B core antigen (HBc)-negative and anti-HCV-positive patient. Control group C was used as the control also for Case group b-C. Serum HBV DNA by molecular hybridization was found more frequently in Control group B (54% of 161 patients) than in Case group B-C (35.7% of 84, P <.01). The prevalence of HBV wild type was similar in Case group B-C (14. 3%) and in Control group B (17.4%), whereas the e-minus strain was less frequent in Case group B-C (10.7% vs. 33%; P <.01). HBV DNA by polymerase chain reaction (PCR) was detected in 40.8% of 71 patients in Case group b-C. HCV RNA was detected more frequently in Control group C (90.7% of 130 patients) than in Case group B-C (65.2% of 69, P <.0001). Moderate or severe chronic hepatitis or cirrhosis were more frequent in Case group B-C (62.9% of 65 patients) than in Control group B (46.7% of 90, P <.05) or C (40.8% of 98, P <.005), and in Case group b-C (71.1% of 76) than in Control group C. Thus, in multiple hepatitis we observed a reciprocal inhibition of the viral genomes and a more severe liver disease. In Case group b-C, serum HBV DNA was frequent and the clinical presentation was severe.

Adult↗

Novel reverse-turn mimics inhibit farnesyl transferase.

Reverse-turn inducing bicyclic lactams were incorporated into the substrate sequence recognized by farnesyl transferase to create inhibitors of RAS farnesylation. While the free peptides did not show any effect on the farnesylation, their Fmoc-protected counterparts impede the transformation of RAS with IC50's in the low micromolar range.

Alkyl and Aryl Transferases↗

Design and synthesis of nonpeptide angiotensin II receptor antagonists featuring acyclic imidazole-mimicking structural units.

Extensive molecular modelling studies, including conformational analysis and the comparison of molecular electrostatic potential distributions, wee used to evaluate structural parameters of new antagonists containing acyclic replacements of the N = C-N imidazole region. The synthesis and the biological screening of a series of acyl biphenyltetrazole derivatives were planned and realized to gain an insight into the structure-activity relationships of this unusual class of Angiotensin II antagonists.

Angiotensin Receptor Antagonists↗

Multiple hepatitis virus infections in chronic HBsAg carriers in Naples.

In order to determine the prevalence of multiple infections with hepatitis viruses in chronic HBsAg carriers in Naples, to assess the interaction between HBV, HDV and HCV infections and to evaluate the influence of multiple virus hepatitis infections on the clinical presentation, we studied 198 HBsAg chronic carriers observed consecutively from 1971 to 1988 at our Liver Unit. Of the 198 HBsAg chronic carriers, 171 had undergone percutaneous liver biopsy. The presence of HBcAg or HDAg in the liver biopsy was considered a marker of HBV or HDV replication, respectively; the presence of anti-HCV was considered a marker of HCV infection. Anti-HCV was observed in 13.6% of the 22 subjects with normal liver, in 27.7% of the 47 patients with minimal chronic hepatitis, in 40% of the 50 with mild chronic hepatitis, in 70.6% of the 17 with moderate hepatitis, in 66.7% of the 3 with severe chronic hepatitis and in 65.6% of the 32 with active cirrhosis. Anti-HCV positive cases were antiHD positive more frequently than the anti-HCV negative (59.2% vs. 43%, p = 0.05). HDV infection exerted a clear inhibition on the HBV genome. Among the 171 HBsAg chronic carriers, the finding of an active chronic hepatitis (moderate chronic hepatitis + severe chronic hepatitis + active cirrhosis) is less frequent in subjects with HBV replication alone than in those with HDV replication or HCV infection. Patients with both HBV replication and HCV infection and those with both HDV replication and HCV infection showed a very high prevelance of active chronic hepatitis.

Adolescent↗

[Serum anti-HIV IgA in seropositive patients and in subjects at risk of HIV infection].

To detect the presence of anti-HIV IgA in HIV infected subjects and in seronegative subjects at risk of infection, we assessed a Western Blot using nitrocellulose strips with HIV separated proteins. We tested at least 2 different serum samples from 9 anti-HIV positive subjects (Group A), 9 anti-HIV negative subjects at risk of infection (Group B) and 9 controls (Group C). One subject in Group B became anti-HIV positive during the observation. Anti-HIV IgA were detected in all patients of Group A, in 66.6% of patients of Group B and in no patient of Group C. The subject who seroconverted during the observation showed positivity for IgA anti-HIV in both serum samples, while anti-HIV IgG became detectable only on the second serum sample. A newborn from a seropositive mother showed maternal anti-HIV IgG on the first 2 out of 3 serum samples while showed anti-HIV IgA positivity on the third sample only. This child is still anti-HIV negative.

English Abstract↗

[Polymerase chain reaction (PCR) for the detection of HIV proviral DNA (pDNA) in subjects at risk of infection].

To detect HlV proviral DNA in lymphocytes from subjects at risk of acquiring HIV infection, we assessed a Polymerase Chain Reaction Assay using the SK38 and SK39 primers for the amplification and the SK19 probe for the hybridization. The detection of amplified HIV-DNA was obtained by a new colorimetric method, the DNA enzyme immunoassay (DEIA). The PCR we performed allowed to detect HIV-pDNA in lymphocytes of 13 out of 64 subjects at risk of acquiring HIV infection. Seven of these 13 became anti-HIV positive during a follow up of 8 months.

English Abstract↗

A 3D QSAR CoMFA study of non-peptide angiotensin II receptor antagonists.

A series of non-peptide angiotensin II receptor antagonists was investigated with the aim of developing a 3D QSAR model using comparative molecular field analysis descriptors and approaches. The main goals of the study were dictated by an interest in methodologies and an understanding of the binding requirements to the AT1 receptor. Consistency with the previously derived activity models was always checked to contemporarily test the validity of the various hypotheses. The specific conformations chosen for the study, the procedures invoked to superimpose all structures, the conditions employed to generate steric and electrostatic field values and the various PCA/PLS runs are discussed in detail. The effect of experimental design techniques to select objects (molecules) and variables (descriptors) with respect to the predictive power of the QSAR models derived was especially analysed.

Angiotensin Receptor Antagonists↗

[Laboratory diagnosis of HIV infection].

The diagnosis of HIV infection is generally lead using two different ELISAs to detect specific anti-HIV antibodies, the eventual reactivity must then be confirmed by a Western Blot The antibodies can be detected only 1-6 months after the infection; in fact in the earliest phases neither the antibodies, for their low titre, nor the specific antigens, for the antibodies could form immune complexes, can be detected by the achieved methods. Only the viral isolation can reveal the presence of the virus in this early phase, but the isolation must be conducted only in adequately safe laboratories (P3 laboratories). The only test able to replace the viral isolation is the Polymerase Chain Reaction (PCR). The PCR technique can be useful to reveal an HIV infection in its early phase and to monitor the infection progression and the efficacy of an antiretroviral treatment

English Abstract↗