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Biomedical subjects

D Ferraro

Publications and source records attributed to D Ferraro.

At least 19 recordsLinked to original sources
PubMed2006

Pro-metastatic signaling by c-Met through RAC-1 and reactive oxygen species (ROS).

Overexpression of the c-Met/hepatocyte growth factor receptor(HGF-R) proto-oncogene and abnormal generation of intracellular oxygen species (reactive oxygen species (ROS)) have been linked, by independent lines of evidence, to cell transformation and to malignant growth. By comparing two subpopulations of the B16 mouse melanoma (B16-F0 and B16-F10) endowed with different lung metastasis capacities (low and high, respectively) we found that both the expression/phosphorylation of c-Met and the steady-state levels of ROS positively correlated with metastatic growth. shRNA-mediated downregulation of c-Met in F10 cells led to a parallel decrease in the generation of oxygen species and in metastatic capacity, suggesting that oxidants may mediate the pro-metastatic activity of the HGF receptor. c-Met activation by a ligand elicits the formation of oxidant species through the oxidase-coupled small GTPase Rac-1, a relevant downstream target of the HGF-R. Moreover, cell treatment with the catalytic ROS scavengers EUK-134 and EUK-189 attenuates Met signaling to ERKs and inhibits the anchorage-independent growth of F10 cells, consistent with a critical role for oxygen species in HGF signaling and in aggressive cell behavior. Finally, genetic manipulation of the Rac-ROS cascade at different levels demonstrated its crucial role in the pro-metastatic activity of c-Met in vivo. Thus, we have outlined a novel cascade triggered by c-Met and mediated by ROS, linked to metastasis and potentially targetable by new antimetastatic, redox-based therapies.

Animals↗
PubMed2005

Multiple attack study on the available triptans in Italy versus placebo.

The aim of the study is to evaluate the efficacy and tolerability of the five triptans that are commercially available in Italy (zolmitriptan 2.5 mg, rizatriptan 10 mg, sumatriptan 100 mg, almotriptan 12.5 mg and eletriptan 40 mg). The study was conducted in single-blind versus placebo and its duration was 18 months. At the Headache Centre of the 'Agostino Gemelli' Hospital in Rome we selected 42 patients, suffering from headache with and without aura (International Headache Society Committee on Headache Classification, 1988 Cephalalgia 8:1-96), whose headache frequency ranged between 1- and 4-monthly crises. For a total of 25 crises, for every five consecutive crises, a different triptan was taken. The end-points of the study were as follows: response at 2 h, 'pain free' at 2 h and 'sustained pain free' (at 24 h). The intra-patient consistency and the tolerability were also evaluated. Thirty patients completed the study and the statistical analysis was only applied to these patients. No substantial difference in terms of the efficacy of the triptans was noted; all triptans were well tolerated. These results suggest the possibility of testing different triptans in the same patient in order to identify the ideal drug for every patient.

Adult↗
PubMed2004

Topiramate in migraine prophylaxis: a randomised double-blind versus placebo study.

The objectives of this paper are to evaluate the efficacy and tolerability of topiramate, given at the dose of 100 mg/day, in the prophylactic treatment of migraine. The hypothesis that migraine is the result of a condition of neuronal hyperexcitability and the quest for drugs that are able to limit the number of crises justifies the attempt to utilise the new antiepileptic drugs in the prophylaxis of this pathology, which is so important due to its high prevalence and due to the high disability it causes. The study was randomised double-blind versus placebo, lasting 16 weeks, and was preceded by a run-in period of 4 weeks. One hundred and fifteen patients were randomly allocated to treatment with topiramate (TPM) or placebo: 35 patients completed the study in the TPM group and 37 patients in the placebo group. At the end of the double-blind phase of study, in the TPM group, we recorded a significant reduction in the frequency of migraine crises (from 5.26 at baseline to 2.60 in the last 4 weeks), a significant reduction in the quantity of symptomatic drugs taken as compared to the placebo control group (from 6.17+/-1.80 SD to 2.57+/-0.80) and a significant downward trend in the number of days of disability over the 16-week period of therapy. In the TPM group, side effects were transient and well tolerated. TPM has thus proven its efficacy and tolerability in the prophylaxis of migraine.

Adult↗
PubMed2003

Occupational head injury and subsequent glioma.

We report the case of a policeman who suffered a severe head injury to the right temporoparietal lobe while driving a police car. Four years later, the patient developed a neoplasm at the precise site of the meningocerebral scar. Histological examination confirmed a glioblastoma multiforme adjacent to the dural scar. Radiological documentation of the absence of tumor at the time of injury, exact localization of the neoplasm in the injured cerebral area, and latency of the cancer supported the hypothesis of a causal relationship with brain trauma. Physicians faced with brain neoplasms in adults should carefully investigate the patient's personal history of head trauma. When a relationship with occupational head injury is probable, reporting of suspect occupational illness is compelling.

Accidents, Occupational↗
PubMed2002

Are hepatitis G virus and TT virus involved in cryptogenic chronic liver disease?

BACKGROUND: Hepatitis G virus can cause chronic infection in man but the role of this agent in chronic liver disease is poorly understood. Little is known about the relation of another newly discovered agent, the TT virus, with chronic liver disease. AIM: To investigate the rate of infection with hepatitis G virus and TT virus in patients with cryptogenic chronic liver disease. PATIENTS: A total of 23 subjects with chronically raised alanine transaminase and a liver biopsy in whom all known causes of liver disease had been excluded, and 40 subjects with hepatitis C virus-related chronic liver disease. METHODS: Evaluation of anti-hepatitis G virus by enzyme immunoassay. Hepatitis G virus-RNA by polymerase chain reaction with primers from the 5' NC and NS5a regions. TT virus-DNA by nested polymerase chain reaction with primers from the ORF1 region. Results. Hepatitis G virus-RNA was detected in 4 out of 23 patients with cryptogenic chronic hepatitis and in 6 out of 40 with hepatitis C virus chronic hepatitis (17.4% vs 15% p=ns). At least one marker of hepatitis G virus infection (hepatitis G virus-RNA and/or anti-hepatitis G virus, mostly mutually exclusive) was present in 6 out of 23 patients with cryptogenic hepatitis and 16 out of 40 with hepatitis C virus liver disease (26. 1% vs 40% p=ns). T virus-DNA was present in serum in 3 subjects, 1 with cryptogenic and 2 with hepatitis C virus-related chronic liver disease. Demographic and clinical features, including stage and grade of liver histology, were comparable between hepatitis G virus-infected and uninfected subjects. Severe liver damage [chronic hepatitis with fibrosis or cirrhosis) were significantly more frequent in subjects with hepatitis C virus liver disease. CONCLUSIONS: In Southern Italy, hepatitis G virus infection is widespread among patients with chronic hepatitis, independently of parenteral risk factors. Its frequency in subjects with cryptogenic liver disease parallels that observed in hepatitis C virus chronic liver disease, thus ruling out an aetiologic role of hepatitis G virus. TT virus infection is uncommon in patients with cryptogenic or hepatitis C virus-related liver disease who do not have a history of parenteral exposure.

Adult↗
PubMed2002

Anti-hepatitis A virus seroprevalence and seroconversion in a cohort of patients with chronic viral hepatitis.

BACKGROUND: Patients with chronic hepatitis C infected by hepatitis A virus have a substantial risk of fulminant hepatitis or death, while the course of hepatitis A virus is uncomplicated in most subjects with chronic hepatitis B. AIM: To evaluate the prevalence of anti-hepatitis A virus antibodies and the incidence of hepatitis A virus seroconversion in a nationwide sample of 530 patients with chronic hepatitis B and/or hepatitis C infection initially susceptible to this infection after a follow-up of some years. RESULTS: The overall anti-hepatitis A virus prevalence was 85.7%, with no difference between males and females. By the age of 50 years, almost all patients were found to have been exposed to hepatitis A virus. After a mean follow-up period of 76 months the overall anti-hepatitis A virus seroconversion rate in the 76 initially susceptible individuals was 1.2 per 100 person/years. However, it was 0.3 per 100 person/years in those hepatitis B surface antigen positive but 3.36 per 100 person/years in those anti-hepatitis C virus positive. None of the seroconverters was affected by a clinically evident disease or showed deterioration of underlying chronic liver disease. CONCLUSIONS: The present study shows that Italian patients >50 years of age with chronic liver disease have already been exposed to hepatitis A virus suggesting that anti-hepatitis A virus screening is not advisable in these subjects.

Adolescent↗
PubMed2002

Early viral clearance and sustained response in chronic hepatitis C: a controlled trial of interferon and ribavirin after high-dose interferon induction.

High-dose induction with alpha-interferon induces early viral clearance of hepatitis C and combined with ribavirin enhances sustained response. We assess whether adding ribavirin after viral clearance obtained by alpha-interferon induction increased the rate of viral eradication.Forty-one naïve patients with chronic hepatitis C were randomised to receive, after 4 weeks of 10 mU daily of alpha-interferon (induction), 3 mU daily for 22 weeks and 3 mU thrice weekly for 26 weeks of either interferon alone (monotherapy) or interferon plus 1000-1200 mg daily of ribavirin (combination therapy). At the end of the induction phase, 23 (56%) subjects had cleared HCV-RNA. During therapy, breakthrough was observed in four patients on monotherapy, but never in patients on combination therapy. The rate of clearance of HCV-RNA was different between monotherapy and combination therapy at the end of treatment (40% vs. 76.1%, P=0.02) and at the end of follow-up (5% vs. 57.1%, P=0.001). Twelve of the 23 patients who cleared HCV-RNA during induction, but only one of the 18 still HCV-RNA-positive after 4 weeks of therapy, had a sustained response (52.2% vs. 5.6%, P=0.001). Clearance of HCV-RNA at 1 week had a high positive predictive value for sustained response in combination therapy (PPV=0.75), but not in monotherapy (PPV=0.33). Induction with high daily doses of alpha-interferon obtains suppression of hepatitis C in more than half of patients, but ribavirin is needed to maintain a sustained response. The rate of sustained response is a function of the time to HCV-RNA clearance. In patients not responding to induction therapy addition of ribavirin does not obtain a sustained virological response.

Adolescent↗
PubMed2001

High-dose prolonged combination therapy in non-responders to interferon monotherapy for chronic hepatitis C.

BACKGROUND: Therapy of chronic hepatitis C non- responders to interferon monotherapy with standard doses of interferon plus ribavirin is usually ineffective. AIM: To evaluate the efficacy and tolerability of high-dose prolonged combination retreatment in non- responder patients. METHODS: Patients were retreated for 6 months with 6 MU alphaIFN on alternate days and 1000 or 1200 mg/day ribavirin. HCV-RNA negative patients continued therapy for an additional 6 months. RESULTS: Forty patients (29 males, mean age 49.7 years, 34 genotype 1b, 11 with F3 fibrosis) were treated. At 6 months, 20 (50%) patients were HCV-RNA negative but six of them discontinued therapy because of adverse events. A sustained response was achieved in 28% of patients (11/40). A sustained response was more frequent among patients with genotype non-1b than in those with genotype 1b (67 vs. 21%, P=0.005) and clearance of HCV-RNA in the first 3 months had a high predictive value for sustained response (100% of sustained responders vs. 24% of non-responders, P=0.0001). CONCLUSIONS: High-dose prolonged combination therapy in non-responders to IFN monotherapy leads to a higher rate of sustained response than the standard combination regimen. Tolerability may be a rate-limiting factor. Maximal effectiveness can be predicted in patients with non-1b genotype and in those who clear HCV-RNA soon after starting retreatment.

Adult↗
PubMed2000

Combined treatment of relapse of chronic hepatitis C with high-dose alpha2b interferon plus ribavirin for 6 or 12 months.

BACKGROUND/AIMS: Retreatment of relapses of chronic hepatitis C with a standard regimen of interferon plus ribavirin for 6 months obtains a sustained response in a minority of patients with high viraemia and genotype 1b. We aimed to assess whether increasing the interferon dose and prolonging the time of combined treatment may enhance the effectiveness, and also to evaluate the tolerability, and to identify the determinants of sustained response. METHODS: Fifty subjects with chronic hepatitis C who had relapsed after one or more courses of a-interferon monotherapy were randomised to receive alpha2b interferon (6 MU tiw) plus ribavirin (1000-1200 mg daily) for 6 or 12 months. ALT normalisation and serum HCV-RNA clearance at the end of treatment and 6 months after stopping therapy were used as markers for sustained response. RESULTS: End-of-treatment response was achieved in 48 patients (96%) and 27 (54%) had a complete sustained response. Patients treated for 12 months had a higher rate of sustained response (18/25, 72%; 95% C.I. 0.54-0.89) than those treated for 6 months (9/25, 36%; 95% C.I. 0.17-0.55, p=0.01). Twelve months of therapy was significantly more effective for patients with genotype 1b and baseline serum HCV-RNA greater than 450 000 copies/ml (p=0.005). Seven subjects (14%) discontinued treatment because of side effects. Logistic regression analysis showed 12 months of therapy, young age and low pre-treatment serum HCV-RNA to be independent predictors of sustained response. CONCLUSIONS: Relapsers with genotype 1b and high levels of HCV-RNA will benefit from a 12-month course of 6 MU tiw interferon plus ribavirin, while subjects with genotype 1b and low levels of serum HCV-RNA or with genotype other than 1b may be treated for 6 months.

Adult↗
PubMed2000

Response-adjusted alpha-interferon therapy for chronic hepatitis C in HIV-infected patients.

In patients with chronic hepatitis C and HIV infection, responsiveness to the standard schedule of alpha-interferon (IFN) is unsatisfactory. To quantify the effectiveness of tailoring IFN dosage according to HCV viral load under treatment, we enrolled 41 patients (M/F 32/9) chronically coinfected by HCV and HIV with chronic liver disease. All were former i.v. drug addicts, with a mean age of 32+/-4 years, and had clinical and histological evidence of chronic hepatitis (10% with cirrhosis). The CDC stage was A1 in five, A2 in 14, A3 in eight, B2 in eight, B3 in three and C3 in three. Twenty four patients were on triple therapy with protease inhibitors, 11 were on two-drug anti-HIV regimens and three were untreated. IFN (alphan1 interferon) was started at 3 MU tiw and increased at 6 MU tiw at 4 weeks if serum HCV-RNA had not dropped by at least 50%. IFN was stopped at 24 weeks in non-responders. Eleven patients received a dose increase (total IFN dose at 24 weeks 396 MU), while 16 did not increase the initial dose (total IFN dose at 24 weeks 216 MU). Fourteen subjects stopped within the first weeks due to relapse of drug abuse (ten) or subjective intolerance (four). ALT and HCV-RNA levels were markedly decreased at week 4, and this reduction lasted up to 24 weeks. However only one patient had a complete biochemical and virological end-of-treatment response, which was maintained over a 24 weeks post-therapy follow-up. All other patients relapsed to baseline ALT and HCV-RNA values after stopping IFN. HIV viral load was slightly reduced under IFN therapy, while CD4 counts were unaffected. We conclude that raising the dose of IFN dose not eradicate HCV in most HIV-infected patients, even when HIV is well controlled by treatment. HCV viraemia and necroinflammation are temporarily suppressed by IFN, but the relevance of these surrogate endpoints to progression of liver disease and to survival cannot be assessed.

Adult↗
PubMed1997

Distribution of VP7 serotypes and VP4 genotypes among rotavirus strains recovered from Italian children with diarrhea.

108 rotavirus strains obtained from children with diarrhea hospitalized in Palermo, Italy, in the years 1990-1994, were examined by seminested PCR to study the relative frequency and distribution of the four most common alleles of the gene 4. Such strains were selected from 344 human rotavirus strains recovered in palermo during those years after characterization by electropherotyping, subgrouping and G serotyping. One hundred and seven of the 108 strains could be classified into P types, the P[8], G1 (38.3%) and the P[8], G4 (52.3%) types being predominant. The unique strain whose P genotype could not be identified showed an unusual combination of long migration electrophoretic pattern and subgroup I specificity.

Antigens, Viral↗
PubMed1996

Identification of picobirnavirus from faeces of Italian children suffering from acute diarrhea.

Polyacrylamide gel electrophoresis of nucleic acid extracted from stool samples of diarrhoeic children revealed in 3 out of 690 (0.43%) specimens two electrophoretic bands with a migration pattern characteristic of picobirnavirus ds-RNA. In none of the 92 control children were similar bands detected. No other potential enteric pathogens were found in the patients with picobirnavirus infection.

Child↗
PubMed1992

Evaluation of DNA probe removal from nylon membrane.

Genetic fingerprinting is one of the most challenging applications of any hybridization membranes. Forensic DNA fingerprinting typically uses samples in the range of 100-400 ng of genomic DNA. To ensure the ability to successfully reprobe the samples, it is imperative that repeated stripping of sample DNA be minimized while stripping of the probe DNA be maximized. By using standard dilutions of K562 cell line, we compared the following three stripping techniques: NaOH at 25 degrees C, formamide (HCONH2) at 65 degrees C and 0.1 x standard saline citrate and 0.1% sodium dodecyl sulfate at 95 degrees C (high-temperature stripping). The largest amount of genomic DNA was stripped from the membrane with NaOH, with the other two techniques removing less. Formamide and high-temperature procedures resulted in a loss of approximately 5-10 ng of DNA per strip. In contrast, the NaOH resulted in a loss of approximately 10-20 ng per strip.

Autoradiography↗
PubMed1990

Binding of flunitrazepam to differentiating neurons cultured in a chemically defined, hormone-supplemented medium.

[3H]Flunitrazepam (FNZ) binding to cortical neurons from fetal rat brain was investigated in vitro. The use of a synthetic medium specific for neurons made it possible to plot a developmental curve of 3H-FNZ binding in an almost pure neuronal culture. Detectable specific binding was present in vitro at time 0 (that is, the 16th gestational day). A progressive increase of binding, due to an increment in the number of recognition sites, was observed on the subsequent days. The affinity of the specific binding sites to 3H-FNZ was enhanced by the addition of exogenous GABA, whereas the density was not affected.

Animals↗
PubMed1990

Triiodothyronine accelerates the synthesis of synapsin I in developing neurons from fetal rat brain cultured in a synthetic medium.

The effect of Triiodothyronine (T3) on Synapsin I appearance in rat cortical neurons has been investigated in vitro. Neuronal cultures from 16-day-old fetal rat brain grown in the absence of T3, express immunohistochemically detectable Synapsin I at the 14th day in vitro. The addition of the hormone to the culture medium determines an early (at the 7th day in vitro) appearance of fluorescent dots specific for Synapsin I.

Animals↗
PubMed1990

[Splenic aneurysm studied by angiography and CT].

An unusual case of an aneurysm on the splenic artery diagnosed as an accessory spleen on the basis of sonographic examination triggers a discussion of sonography, CT and angiography in the diagnosis of splenic aneurysms, which though rare in absolute term constitute a real threat to the patient's life giving her [correction of him] a high percentage of spontaneous ruptures when they do occur.

Aneurysm↗