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Biomedical subjects

G Gallo

Publications and source records attributed to G Gallo.

At least 37 records · Page 2Linked to original sources

Distinct properties of wild-type and the amyloidogenic human cystatin C variant of hereditary cerebral hemorrhage with amyloidosis, Icelandic type.

Variant human cystatin C (L68Q) is an amyloidogenic protein. It deposits in the cerebral vasculature of Icelandic patients with cerebral amyloid angiopathy, leading to stroke. Wild-type and variant cystatin C are cysteine proteinase inhibitors which form concentration dependent inactive dimers; however, variant cystatin C dimerizes at lower concentrations and has an increased susceptibility to a serine protease. We studied the effect of the L68Q amino acid substitution on cystatin C properties, utilizing full length cystatin C purified in mild conditions from media of cells stably transfected with either the wild-type or variant cystatin C genes. The variant cystatin C forms fibrils in vitro detectable by electron microscopy in conditions in which the wild-type protein forms amorphous aggregates. We also show by circular dichroism, steady-state fluorescence and Fourier-transformed infrared spectroscopy that the amino acid substitution modifies cystatin C structure by destabilizing alpha-helical structures and exposing the tryptophan residue to a more polar environment, yielding a more unfolded molecule. These spectral changes demonstrate that variant cystatin C has a three-dimensional structure different from that of the wild-type protein. The structural differences between variant and wild-type cystatin C account for the susceptibility of the variant protein to unfolding, proteolysis and fibrillogenesis.

Amino Acid Substitution↗

Renal hemodynamic response to maximal vasodilating stimulus in healthy older subjects.

BACKGROUND: It is still unclear whether age per se is associated with preservation of renal functional reserve, that is, of the increase in glomerular filtration rate (GFR) induced by appropriate vasodilating stimulus. METHODS: To gain insights into this issue, we evaluated the renal response to a maximal vasodilating stimulus, represented by the combined infusion of mixed amino acid solution (AA) and dopamine at renal dose (D), in 10 young subjects (median age of 30 years, range of 19 to 32) and in 11 subjects of older age (median age of 67 years, range of 65 to 76). Two further age-matched groups of young (N = 15) and older (N = 11) living kidney donors underwent renal needle biopsy immediately before nephrectomy to perform semiquantitative scoring (0 to 3) of arteriosclerosis in intrarenal arteries. All of the study subjects were nonsmokers with healthy status proven by extensive diagnostic evaluation excluding any risk factor of renal dysfunction. RESULTS: Basal renal plasma flow (RPF) and GFR were proportionally lower in older subjects (RPF, 361 +/- 29 vs. 618 +/- 34 mL/min/1.73 m(2), P < 0.001; GFR, 79 +/- 4 vs. 127 +/- 5.8 mL/min/1.73 m(2), P < 0.001). After AA + D, a significant increase of RPF and GFR was observed in both groups, but the older subjects exhibited a smaller percentage increment (RPF, 25.5 +/- 4.8 vs. 42.4 +/- 5.8, P < 0.05; GFR, 19.6 +/- 5.7 vs. + 33.8 +/- 6.4, P < 0.05). Furthermore, the maximal vasodilating stimulus was not able to restore renal hemodynamics in older subjects to the level measured in young controls at baseline. Renal vascular resistances were higher (P < 0.05) in the older subjects both at baseline (0.19 +/- 0.02 vs. 0.09 +/- 0.004 mm Hg/mL/min) and after AA + D (0.14 +/- 0.01 vs. 0.06 +/- 0.004). Light microscopy examination detected the presence of a greater degree of arteriosclerosis at the level of interlobular and arcuate arteries (0.89 +/- 0.15 vs. 0.45 +/- 0.08) and interstitial fibrosis/tubular atrophy (1.18 +/- 0.13 vs. 0.53 +/- 0.13) in older than in young subjects. CONCLUSIONS: Therefore, aging has adverse effects on renal function despite the absence of any risk factor for renal disease, including chronic smoking: (1) GFR and RPF are lower, and (2) the renal response to maximal vasodilating stimulus is impaired. These aging-related alterations of renal hemodynamics are possibly due to organic lesions in renal vasculature.

Adult↗

Codeposition of cystatin C with amyloid-beta protein in the brain of Alzheimer disease patients.

Immunohistochemical analysis of brains of patients with Alzheimer disease (AD) revealed that the cysteine proteinase inhibitor cystatin C colocalizes with amyloid beta-protein (Abeta) in parenchymal and vascular amyloid deposits. No evidence of cerebral hemorrhage was observed in any of the brains studied. Immunoelectron microscopy demonstrated dual staining of amyloid fibrils with anti-Abeta and anti-cystatin C antibodies. Cystatin C immunoreactivity was also observed in amyloid deposits in the brain of transgenic mice overexpressing human beta amyloid precursor protein. Massive deposition of the variant cystatin C in the cerebral vessels of patients with the Icelandic form of hereditary cerebral hemorrhage with amyloidosis is thought to be responsible for the pathological processes leading to stroke. Anti-cystatin C antibodies strongly labeled pyramidal neurons within cortical layers most prone to amyloid deposition in the brains of AD patients. Immunohistochemistry with antibodies against the carboxyl-terminus of Abeta(x-42) showed intracellular immunoreactivity in the same neuronal subpopulation. It remains to be established whether the association of cystatin C to Abeta plays a primary role in amyloidogenesis of AD or is a late event in which the protein is bound to the previously formed Abeta amyloid fibrils.

Aged↗

Surface interactions between Escherichia coli and hemocytes of the Mediterranean mussel Mytilus galloprovincialis lam. leading to efficient bacterial clearance.

The role of type 1 fimbriae in the interactions between Escherichia coli and Mytilus galloprovincialis Lam. hemocytes was evaluated. The association of fimbriated strain MG155 with hemocyte monolayers at 18 degrees C was 1.5- and 3- to 4-fold greater than the association of unfimbriated mutant AAEC072 in artificial seawater and in hemolymph serum, respectively. Such differences were apparently due to different adhesive properties since MG155 adhered more efficiently than AAEC072 when hemocytes were incubated at 4 degrees C to inhibit the internalization process. Hemolymph serum increased both association and adherence of MG155 two- to threefold but did not affect association and adherence of AAEC072. MG155 was also 1.5- to 1.7-fold more sensitive to killing by hemocytes than AAEC072, as evaluated by the number of culturable bacteria after 60 and 120 min of incubation. The role of type 1 fimbriae in MG155 interactions with hemocytes was confirmed by the inhibitory effect of D-mannose. In in vivo experiments MG155 cells were cleared from circulating hemolymph more rapidly than AAEC072 cells were cleared. These results confirm that surface properties are crucial in influencing bacterial persistence and survival within mussel hemolymph.

Animals↗

Sexually transmitted infections and cervicovaginal dysplasia in a cohort of human immunodeficiency virus-positive women in Turin.

The correlation between sexually transmitted infections and cervicovaginal dysplasia has been evaluated in a cohort of 135 women who tested positive for human immunodeficiency virus type I (HIV-1) and were admitted to Amedeo di Savoia Hospital of Turin during the years 1997 and 1998 (stages B2 and B3 or C2 and C3). Of these women. 31 presented with sexually transmitted diseases (STDs; mean age, 33.5 +/- 5.9 years). Among them, 14 were affected by cervicovaginal dysplasia of differing severity; human papillomavirus (HPV) infection was found in 13 subjects (10 with cervicovaginal dysplasia). Herpes simplex virus type 2 (HSV-2) infection was detected in six women. Finally, Trichomonas vaginalis and Candida albicans were found in 10 and in 6 patients, respectively. Immunologic and hematologic evaluations were performed in the patients affected by STDs; in 28 patients of our case report unaffected by STDs but of similar ages (34.1 +/- 5.6 years) and stage of infection; and in 20 HIV-negative women unaffected by STDs. A significant reduction among the patients affected by STDs, as compared to those unaffected, was found in the case of white cells, CD4+ T cells, and ratio values (CD4 +/ and CD8 + T cells). Moreover, red cell count and hemoglobin concentration were lower in those women in the STD group. A lack of correlation was found between HIV RNA loads and CD4 + T cell counts and between HIV RNA and hemoglobin concentration in the patients with cervicovaginal dysplasia and in those affected by HSV-2 infection, which differed from the findings in subjects affected only by trichomoniasis or candidiasis. This suggests that the two former pathologic conditions (cervico-vaginal dysplasia and HSV-2 infection), other than HIV- I infection, may contribute to the impairment of these values. Moreover in our case report, T vaginalis and HSV-2 infections, which are suspected to have an oncogenic potential, do not seem to be relevant in the induction or facilitation of genital neoplastic diseases. Noteworthy is that the patients affected by HSV-2 infection, such as those affected by genital neoplastic diseases, showed the most compromised values of total white cells, CD4+ T cells, ratio index, red cells, and hemoglobin concentration.

Adult↗

[Heart failure in nursing homes: prevalence, hospitalization, compliance to guidelines].

BACKGROUND: The prevalence of heart failure, the hospitalization rates for DRG 127 and the adherence to the recommendations included in the guidelines on pharmacological treatment among very old persons are poorly known. METHODS: We screened 141 very old subjects (75% females, aged 87+/-4 years), living in 2 nursing homes. Heart failure was defined according to clinical criteria and on the basis of administrative databases and chart reviews. The latter were also used to collect data on hospitalization rates and pharmacological therapy. RESULTS: We found that: 1) 23% of the subjects were affected by heart failure; 2) with regard to such patients, 26 hospital admissions for DRG 127 occurred in 1999 (18 admissions and 8 readmissions; 3) ACE-inhibitors have been prescribed to 54% of patients with a diagnosis of heart failure. CONCLUSIONS: Heart failure affects a huge number of very old persons living in nursing homes. These patients have high hospitalization rates for DRG 127. The adherence to the recommendations included in the guidelines on the pharmacological therapy for very old persons is poor.

Aged↗

Deriving a quantitative chirality measure from molecular similarity indices.

A versatile new method has been developed as a continuous symmetry measure for chiral compounds. The application of principal component analysis (PCA) to the complete N x N pairwise similarity matrices (electrostatic potential and shape indices) of a series of dihydropyridine calcium channel antagonists allowed to single out a chirality component and to compute a chirality score in terms of the between-enantiomers difference on the component value. The possibility to have chirality defined continuously at the series level could be of importance in eudismic analyses where the relative potency of two enantiomers is studied as well as in QSAR studies dealing with chiral molecules in order to improve the power of the generated models.

Calcium Channel Blockers↗

Nasopharyngeal carcinoma in childhood and adolescence: a single-institution experience with combined therapy.

BACKGROUND: A high cure rate may be attained for locally advanced, undifferentiated nasopharyngeal carcinoma (NPC) in children, provided that a combined modality of treatment is employed. Both local and systemic therapies are necessary. Results at a single pediatric institution were analyzed. METHODS: From November 1988 to December 1997, 16 consecutive patients were treated with NPC at the Hospital Garrahan in Buenos Aires, Argentina. The authors were able to evaluate 11 patients (9 boys and 2 girls); their median age was 12 (range, 8-14) years. Chemotherapy consisted of 3 courses, every 3 weeks, of 5-fluorouracil (500 mg/m(2)) plus bleomycin (15 mg/m(2)) daily for 4 days, with cisplatin (100 mg/m(2)) added the last day. External beam radiotherapy was delivered over a median of 52 (range, 45-63) days, to a median cumulative dose to the primary site of 55 (range, 50-61.2) grays (Gy). The median dose for the lower neck area was 45 (range, 45-55.8) Gy. All patients received radiotherapy to the primary site and to the initially involved lymphoid areas, with daily single doses of 1.8 Gy (5 of 7 days per week). RESULTS: The main symptoms at onset were cervical mass (100%), epistaxis (54%), cephalalgia (36%), and trismus (36%). All cases were Stage IV (American Joint Committee on Cancer and International Union Against Cancer TNM system). Complete response was achieved in 45% of patients after initial chemotherapy. With a median follow-up of 63 (range, 23-119) months, disease free survival (with standard error [SE]) and overall survival estimates were 61% (16%) and 91% (9%), respectively, at 75 months. Acute toxicity due to therapy was tolerable. Chronic sinusitis (73%), hypothyroidism (73%), and mild (64%) or moderate (9%) neck fibrosis were detected at follow-up. CONCLUSIONS: Although this series is small, the authors concluded that NPC patients have a good chance of survival in the setting described, in spite of locally advanced disease. Chemotherapy might be useful in preventing the development of systemic metastases.

Adolescent↗

Immunoelectron microscope analysis of epidermal growth factor receptor (EGFR) in isolated Mytilus galloprovincialis (Lam.) digestive gland cells: evidence for ligand-induced changes in EGFR intracellular distribution.

In mammalian cells, the binding of epidermal growth factor (EGF) to its receptor (EGFR), a glycoprotein with intrinsic tyrosine kinase activity, leads to the pleiotropic responses to EGF. Among these, a negative feedback response by stimulation of receptor internalization and lysosomal degradation, this attenuating signal transduction. In this work, data are reported on the identification of specific EGFRs in isolated digestive gland cells from the marine mussel (Mytilus galloprovincialis Lam.) By immunoelectron microscopy. In control digestive cells, EGFR immunoreactivity was mainly associated with cytoplasmic membrane structures and, to a lesser extent, the cell membrane. The presence of EGFR-like receptors was confirmed by Western blotting of digestive gland cell extracts with two different monoclonal antibodies that recognize either intracellular or extracellular epitopes. The addition of mammalian EGF resulted in significant time and temperature-dependent changes in EGFR subcellular distribution in mussel cells. In cells exposed to EGF for 0-15 min at 4 degrees C, the distribution of EGFR was not significantly different from that of the control cells. On the other hand, at 18 degrees C, an increased labelling along the cell membrane was observed after 5-10 min after EGF addition, with a concomitant decrease in the cytoplasmic signal. Moreover, after 20 min of exposure to EGF, ligand binding apparently resulted in EGFR compartmentation within the lysosomes. These observations were confirmed by quantitative analysis of EGFR labelling at different times of EGF exposure. Similar results were obtained utilizing the two different monoclonal antibodies. The results indicate that, in mussel digestive cells, the binding of heterologous EGF to specific receptors induces a negative feedback response by stimulating the lysosomal degradation of EGFR, thus suggesting the presence of mechanisms responsible for receptor downregulation similar to those observed in mammalian cells.

Animals↗

Hg(2+) and Cu(2+) interfere with agonist-mediated Ca(2+) signaling in isolated Mytilus digestive gland cells.

The effects of mercury and copper on agonist-mediated Ca-signaling were investigated in isolated cells from the marine mussel, Mytilus galloprovincialis Lam., by single cell fluorescence microscopy. In isolated digestive gland cells, short-term exposure (10 min) to both Hg(2+), a highly toxic metal and Cu(2+), an essential metal, in the nano-low µM range caused a sustained increase in cytosolic [Ca(2+)]. The effect of mercury on resting [Ca(2+)] was stronger than that of copper. The Hg-induced elevation in [Ca(2+)] seemed to be mainly due to an increased influx through Verapamil-sensitive Ca-channels, whereas the effect of Cu(2+) was related to a release from thapsigargin-sensitive intracellular stores. Agonists, such as epidermal growth factor (EGF), bradykinin (BK) and ATP, evoked Ca(2+) transients in isolated digestive gland cells through different mechanisms similar to those observed in mammalian cells, demonstrating the presence of common pathways of Ca-mediated cell signaling in both invertebrates and vertebrates. The agonist-mediated Ca(2+) response was affected by exposure to Hg(2+) and Cu(2+) in a concentration dependent manner: both metals significantly reduced the amplitude of the Ca(2+) spikes elicited by BK and ATP and decreased the percentage of EGF-responsive cells. The effects of Hg(2+) and Cu(2+) were apparently independent of their different type of interaction with the mechanisms involved in Ca(2+) homeostasis. The results clearly demonstrate that, in marine invertebrate cells, short-term exposure to heavy metal concentrations comparable to environmental exposure levels results in alterations of intracellular Ca(2+) homeostasis which compromise the cell response to extracellular stimuli involving Ca-mediated signaling. The mechanisms of heavy metal interference with Ca-homeostasis and signaling are discussed.

Journal Article↗

Stabilization of growing retinal axons by the combined signaling of nitric oxide and brain-derived neurotrophic factor.

The pattern of axonal projections early in the development of the nervous system lacks the precision present in the adult. During a developmental process of refinement, mistargeted projections are eliminated while correct projections are retained. Previous studies suggest that during development nitric oxide (NO) is involved in the elimination of mistargeted retinal axons, whereas brain-derived neurotrophic factor (BDNF) may stabilize retinal axon arbors. It is unclear whether these neuromodulators interact. This study showed that NO induced growth cone collapse and retraction of developing retinal axons. This effect was not attributable to NO-induced neurotoxicity. BDNF protected growth cones and axons from the effects of NO. This effect was specific to BDNF, because neither nerve growth factor (NGF) nor neurotrophin-3 (NT-3) prevented NO-induced growth cone collapse and axon retraction. Exposure to both BDNF and NO, but not either factor alone, stabilized growth cones and axons. Stabilized axons exhibited minimal retraction or extension. This response appears to be a new axon "state" and not simply a partial amelioration of the effect of NO, because lower doses of BDNF or NO allowed axon extension. Furthermore, BDNF/NO-induced growth cone stabilization correlated with the appearance of a cytochalasin D-resistant population of actin filaments. BDNF protection from NO likely was mediated locally at the level of the growth cone, because growth cones or individual filopodia in contact with BDNF-coated beads were protected from NO-induced collapse. These findings suggest a cellular mechanism by which some axonal connections are stabilized and some are eliminated during development.

Animals↗

Neurotrophins and the dynamic regulation of the neuronal cytoskeleton.

The morphology of neuronal axons and dendrites is dependent on the dynamics of the cytoskeleton. An understanding of neurodevelopment and adult neuroplasticity must therefore include a detailed description of the intrinsic and extrinsic mechanisms that regulate the organization and dynamics of actin filaments and microtubules. In this paper we review recent advances in the understanding of the dynamic regulation of neuronal morphology by interactions among cytoskeletal components and the regulation of the cytoskeleton by neurotrophins.

Animals↗

Senile dementia associated with amyloid beta protein angiopathy and tau perivascular pathology but not neuritic plaques in patients homozygous for the APOE-epsilon4 allele.

Amyloid beta protein deposition in cortical and leptomeningeal vessels, causing the most common type of cerebral amyloid angiopathy, is found in sporadic and familial Alzheimer's disease (AD) and is the principal feature in the hereditary cerebral hemorrhage with amyloidosis, Dutch type. The presence of the Apolipopriotein E (APOE)-epsilon4 allele has been implicated as a risk factor for AD and the development of cerebral amyloid angiopathy in AD. We report clinical, pathological and biochemical studies on two APOE-epsilon4 homozygous subjects, who had senile dementia and whose main neuropathological feature was a severe and diffuse amyloid angiopathy associated with perivascular tau neurofibrillary pathology. Amyloid beta protein and ApoE immunoreactivity were observed in leptomeningeal vessels as well as in medium-sized and small vessels and capillaries in the parenchyma of the neocortex, hippocampus, thalamus, cerebellum, midbrain, pons, and medulla. The predominant peptide form of amyloid beta protein was that terminating at residue Val40, as determined by immunohistochemistry, amino acid sequence and mass spectrometry analysis. A crown of tau-immunopositive cell processes was consistently present around blood vessels. DNA sequence analysis of the Amyloid Precursor Protein gene and Presenilin-1 (PS-1) gene revealed no mutations. In these APOE-epsilon4 homozygous patients, the pathological process differed from that typically seen in AD in that they showed a heavy burden of perivascular tau-immunopositive cell processes associated with severe amyloid beta protein angiopathy, neurofibrillary tangles, some cortical Lewy bodies and an absence of neuritic plaques. These cases emphasize the concept that tau deposits may be pathogenetically related to amyloid beta protein deposition.

Aged↗

The impact of the hepatitis B mass immunisation campaign on the incidence and risk factors of acute hepatitis B in Italy.

BACKGROUND/AIMS: This study aimed to evaluate the impact of the campaign for hepatitis B mass immunisation of children and teenagers, introduced in 1991, on the incidence of and risk factors for hepatitis B in Italy. METHODS: Hepatitis B cases reported to the surveillance system for type-specific acute viral hepatitis (SEIEVA) during the period 1987-1997 were used to estimate incidence. To assess the association between potential risk factors and hepatitis B cases, hepatitis A cases generated by the same surveillance system were used as controls. RESULTS: During the period 1987-1997, 8275 acute hepatitis B cases were reported to SEIEVA. Hepatitis B incidence declined from 10.4/100,000 in 1987 to 2.9/100,000 in 1997. The fall was more evident before than after the introduction of compulsory vaccination against hepatitis B. The results of multivariate analysis showed that during the years 1995-1997, blood transfusion, intravenous drug use, surgical intervention, dental therapy, other parenteral exposures, multiple sexual partners, and being in the household of a chronic HBsAg carrier were all exposures independently associated with hepatitis B. CONCLUSIONS: The strong association linking acute hepatitis B with iatrogenic exposures, which are more common in adults, suggests that the present immunisation strategy should be combined with the implementation of non-immunologic preventive measures.

Acute Disease↗

Growth factor-mediated signal transduction and redox balance in isolated digestive gland cells from Mytilus galloprovincialis Lam.

In mammalian cells, a growing body of evidence indicates a relationship between cellular redox balance and tyrosine kinase-mediated cell signalling. The phosphorylative cascade activated by extracellular signals is inhibited by reducing conditions and stimulated by oxidative stress, in particular at the level of mitogen activated protein kinase (MAPK) activation. The mussel Mytilus typically shows variations in antioxidant defence systems and decreases in glutathione content in response to both natural and contaminant environmental stressors. In isolated mussel digestive gland cells, both epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) have been recently demonstrated to activate tyrosine kinase receptors leading to multiple responses; among these, stimulation of the key glycolytic enzymes phosphofructokinase (PFK) and pyruvate kinase (PK). The present study investigates the possible relationship between the tyrosine kinase-mediated metabolic effects of growth factors and cellular redox balance in mussel cells. The results demonstrate that the effects of growth factors on glycolytic enzymes were abolished by cell pretreatment with the antioxidant N-acetyl-cysteine (NAC). On the other hand, in cells where the glutathione content and synthesis were lowered either in vitro (by cell pretreatment with buthionine sulfoximine (BSO)), or in vivo (by mussel exposure to Cu(2+)) the metabolic effects of growth factors were unaffected. Moreover, the results show that, in both control and glutathione-depleted cells, growth factors can also regulate the level of glutathione apparently by modulating, via phosphorylative mechanisms involving MAPK activation, the activity of gamma-glutamylcysteine synthetase (GCS), the rate limiting enzyme in GSH biosynthesis. Overall, this study extends the hypothesis that cell signalling is intimately related to redox balance in marine invertebrate cells.

Acetylcysteine↗

Hepatic arterial thrombosis due to Mucor species in a child following orthotopic liver transplantation.

Infection is a frequent complication in patients following liver transplantation, and mycotic etiology is the third most common cause. Thrombosis of the hepatic artery is a high-risk condition for the graft and is generally secondary to noninfectious diseases. We present a 2-year-old child who developed hepatic artery obstruction due to Mucor sp. The child did not respond to medical treatment. We conclude that a high index of suspicion and rapid diagnosis are required so that aggressive and early treatment can be initiated. To our knowledge this is the first case published with this particular association.

Fatal Outcome↗

Prevention of hepatitis C in Italy: lessons from surveillance of type-specific acute viral hepatitis. SEIEVA collaborating Group.

Using data from the surveillance system for type-specific acute viral hepatitis, the temporal incidence trend of non-A, non-B acute hepatitis and risk factors for acute hepatitis C have been evaluated in Italy. The association between hepatitis C and the potential risk factors (odds ratios, OR) was estimated using hepatitis A patients as controls. The independent roles of the different risk factors were estimated by multiple logistic regression analysis. The incidence of non-A, non-B acute hepatitis declined from 5 per 100 000 to 1 per 100 000 between 1985 and 1996. Anti-HCV data collected by SEIEVA since 1991 showed that 60% of patients with non-A, non-B acute hepatitis were positive for antibodies to the hepatitis C virus (anti-HCV) at the time of hospitalization. During the 6 months prior to the disease onset, the most frequently reported risk factors were multiple sexual partners, other parenteral exposure and intravenous drug use; transmission by blood transfusion declined from 20% in 1985 to 2% in 1996. On multivariate analysis, intravenous drug use (OR=35.5; 95% CI=23.1-54.4), surgical intervention (OR=4.6; 95% CI=3.3-6.5), dental treatment (OR=1.5; 95% CI=1.1-1.9) and two or more sexual partners (OR=2.2; 95% CI=1.6-3.0) were all independent predictors of hepatitis C. These findings indicate that HCV infection is decreasing in Italy. Intravenous drug use, multiple sexual partners, surgical intervention and dental therapy are the main modes of transmission.

Adolescent↗