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Biomedical subjects

G Ghigliotti

Publications and source records attributed to G Ghigliotti.

At least 19 recordsLinked to original sources
PubMed2005

Molecular characterization of Italian nevoid basal cell carcinoma syndrome patients.

Mutations in the PTCH gene, the human homolog of the Drosophila patched gene, have been found to lead to the autosomal dominant disorder termed Nevoid Basal Cell Carcinoma Syndrome (NBCCS, also called Gorlin Syndrome). Patients display an array of developmental anomalies and are prone to develop a variety of tumors, with multiple Basal Cell Carcinomas occurring frequently. We provide here the results of molecular testing of a set of Italian Nevoid Basal Cell Carcinoma Syndrome patients. Twelve familial patients belonging to 7 kindreds and 5 unaffected family members, 6 non-familial patients and an additional set of 7 patients with multiple Basal Cell Carcinoma but no other criteria for the disease were examined for mutations in the PTCH gene. All of the Nevoid Basal Cell Carcinoma Syndrome patients were found to carry variants of the PTCH gene. We detected nine novel mutations (1 of which occurring twice): 1 missense mutation (c.1436T>G [p.L479R]), 1 nonsense mutation (c.1138G>T [p.E380X]), 6 frameshift mutations (c.323_324ins2, c.2011_2012dup, c.2535_2536dup, c.2577_2583del, c.3000_3005del, c.3050_3051del), 1 novel splicing variant (c.6552A>T) and 3 mutations that have been previously reported (c.3168+5G>A, c.1526G>T [p.G509V], and c.3499G>A [p.G1167R]). None of the patients with multiple Basal Cell Carcinoma but no other criteria for the syndrome, carried germline coding region mutations.

Adolescent↗
PubMed2004

Reduction of cardiovascular morbidity and mortality in type 2 diabetes. A rational approach to hypoglycemic therapy.

Type 2 diabetes mellitus is the single most important risk factor for the development of coronary artery disease. Unfortunately, the traditional therapeutic strategies for the treatment of hyperglycemia have proven to be ineffective in preventing cardiovascular complications. In recent years the number of available hypoglycemic agents has increased and considerable progress has been made regarding the comprehension of the pathophysiology of diabetes and its vascular complications. In the present article we firstly present benefits and risks of intensive vs standard hypoglycemic intervention, and the pros and cons of therapy targeted to postprandial hyperglycemia. Secondly, we discuss the cardiovascular effects of sulfonylurea agents and insulin, focusing on the role of intensive insulin treatment in the context of acute coronary syndromes. Thirdly, we review the epidemiological, clinical and experimental evidence linking insulin resistance and cardiovascular disease. Finally, we present the rationale and the role of metformin and thiazolidinedionetherapy in the prevention of cardiovascular complications. We conclude that the optimal use of the full spectrum of hypoglycemic agents has the potential to play a key role in the prevention of diabetes-related macrovascular complications.

Blood Glucose↗
PubMed2003

Metalloproteinases 2 and 9 are increased in plasma of patients with heart failure.

BACKGROUND: Progression of heart failure is associated with interstitial changes in the heart and in areas distant from the heart. Enhanced expression of metalloproteinases 2 and 9 and of metalloproteinases tissue inhibitors 1 and 2 have been found in ventricular tissue of patients with heart failure. Our aim was to determine whether increased activity of metalloproteinase-2, metalloproteinase-9 and of metalloproteinases tissue inhibitor-1 and metalloproteinases tissue inhibitor-2 were also present in plasma of patients with heart failure. DESIGN: Levels of metalloproteinase-2, metalloproteinase-9 and of metalloproteinase tissue inhibitor-1 and metalloproteinases tissue inhibitor-2 were measured in venous blood of 51 patients with heart failure, and were compared with levels of 52 control subjects. Samples collected from patients and control subjects were assayed for gelatinolytic activity (zymography) and for protein levels. RESULTS: Compared with the control subjects, the patients with heart failure had a significant increase in activity levels (mean +/- SE, ng mL(-1)) of prometalloproteinase-9 (95.1+/-11.2 and 38.9+/-4.5*), activ. metalloproteinase-9 (18.4+/-2.5 and 10.9+/-1.3*), and of prometalloproteinase-2 (571.4+/-26.1 and 456.8+/-21.1*) (respectively: patients and control subjects; *P<0.05). Metalloproteinases tissue inhibitor-1, but not metalloproteinases tissue inhibitor-2 protein values were higher in the patients. Among the patients, clinical status and New York Heart Association (NYHA) class did not correlate with the metalloproteinase concentrations. Positive correlations with left ventricular volumes, and negative correlations with lipid values were obtained for prometalloproteinase-2; positive correlations with total number of white cells and neutrophils were obtained for prometalloproteinase-9; and positive correlations with lactate dehydrogenase, serum fibrinogen, aspartate transaminases were found for activ. metalloproteinase-9. CONCLUSIONS: Regardless of the clinical phase of heart failure, elevated levels of activity and of circulating metalloproteinase protein levels suggest the presence of persistent extracellular remodeling in patients with heart failure.

Aged↗
PubMed2002

High doses of atorvastatin do not affect activity of prothrombinase in patients with acute coronary syndromes.

Membrane-dependent coagulation processes play a key role in acute coronary syndromes (ACS), where the generation of thrombin depends on the complex of activated factors X and V (prothrombinase complex) assembled on activated platelets. The aim of the present study was to evaluate prothrombinase activity in patients with ACS and to examine the effect of treatment with 80 mg/day atorvastatin on prothrombinase activity. Blood samples were obtained at admission from 22 patients with ACS, and then again at 2 weeks and at 16 weeks after double-blind randomization to either placebo or atorvastatin. Prothrombinase activity was evaluated by measuring the generation of thrombin by in vitro reconstructed thrombi, and also by measuring plasma levels of prothrombin fragment F1 + 2. Twenty age-matched subjects with stable angina and 11 without coronary disease were used as controls. At admission, prothrombinase activity and F1 + 2 were significantly higher in ACS patients than in controls. Prothrombinase activity was still high at 2 weeks while it returned to normal levels at 16 weeks. F1 + 2 remained high both at 2 and at 16 weeks. Our data indicate that prothrombinase activity is high in patients with ACS, and that it is not affected by high-dose atorvastatin.

Acute Disease↗
PubMed2001

Maximal endothelial tissue plasminogen activator release is not impaired in patients with acute coronary syndromes before heparin treatment.

Procoagulant and fibrinolytic disturbances are described in patients with acute coronary syndromes (ACS), but whether defective maximal tissue plasminogen activator (t-PA) release from the endothelium is also present is still controversial. Previous studies did not take into consideration the contribution of heparin, which strongly affects fibrinolysis. Accordingly, in this study, we measured maximal t-PA release in patients with ACS before, during, and after heparin treatment. Maximal t-PA release was measured by the venous occlusion test in 38 hospitalized patients with confirmed ACS (18 acute myocardial infarctions and 20 unstable anginas) before starting heparin, during heparin treatment, and 4 and 12 h after discontinuation. Plasma plasminogen activator inhibitor type 1 (PAI-1), D-dimer and prothrombin fragment F1 + 2 were also measured. Eighteen age-matched subjects with no evidence of coronary disease were used as controls. At admission, patients showed significantly higher plasma levels of t-PA, PAI-1, and F1 + 2 than controls. Before heparin, maximal t-PA release was similar in patients and controls. Heparin treatment was associated with a significant increase of plasma t-PA, while it did not affect maximal t-PA release. Coagulative and fibrinolytic disturbances are present in patients with ACS, but these do not include maximal t-PA release. Among our patients, maximal t-PA release appears stable over time and is not affected by heparin treatment.

Aged↗
PubMed2001

N-acetyl-cysteine reduces neointimal thickening and procoagulant activity after balloon-induced injury in abdominal aortae of New Zealand white rabbits.

BACKGROUND: Procoagulant activity and oxidative stress generated by balloon injury to normal vessels promote the migration of medial smooth muscle cells and their proliferation in the intima. We hypothesised that administering levo N-acetyl-cysteine (NAC) i.v. at the time of injury, and s.c. before and after injury would reduce neointimal formation 4 weeks later and would regulate procoagulant activity in vessels with neointima undergoing ballooning a second time. METHODS AND RESULTS: at the time of injury rabbits received: NAC, unfractionated heparin (HEP) or both (NAC + HEP). Neointimal thickening at 28 days, calculated as the ratio between the intimal and medial area, was attenuated after NAC, HEP and NAC+HEP by 39%, 30% and 47% respectively when compared to untreated injured animals (CONTROLS) (p <0.05). At 28 days, bound thrombin activity and platelet adhesion 1 h after a repeated balloon injury decreased in animals receiving NAC, HEP and NAC+HEP bv 54%, 63% and 64% for thrombin activity (p <0.05 vs CONTROLS), and by 56%, 66% and 75% respectively for 111Indium-platelet deposition (p <0.05 vs CONTROLS). CONCLUSIONS: NAC in-vivo was effective in reducing neointimal thickening and procoagulant response after balloon injury.

Acetylcysteine↗
PubMed2000

Papular-purpuric gloves and socks syndrome in HIV-positive patients.

Three HIV-positive women showed clinical signs of papular-purpuric gloves and socks syndrome and serologic evidence of acute Parvovirus B19 infection. The course of the disease was complicated by anemia and persistent skin lesions, probably related to inadequate immune response. Because anemia in AIDS patients may be due to many causes, the history of recent Parvovirus B19 infection is helpful in suggesting the etiologic diagnosis.

AIDS-Related Opportunistic Infections↗
PubMed2000

p53 mutations experimentally induced by 8-methoxypsoralen plus UVA (PUVA) differ from those found in human skin cancers in PUVA-treated patients.

8-Methoxypsoralen (8-MOP) plus UVA irradiation (PUVA therapy) has been used for the treatment of psoriasis. PUVA therapy has been associated with an increased risk of developing skin squamous cell carcinoma (SCC). In order to determine the PUVA-induced p53 mutation spectrum, a yeast expression vector harbouring a human wild-type p53 cDNA was incubated with 8-MOP, and UVA irradiated in vitro. PUVA-damaged and undamaged DNA was transfected into a yeast strain containing the ADE2 gene regulated by a p53-responsive promoter. An 8-MOP concentration-dependent decrease in survival and increase in mutant frequency were observed. At a fixed 8-MOP concentration, survival decreased and mutant frequency increased as UVA irradiation increased. Eleven mutant clones contained 11 mutations: 10 were single base pair substitutions, the remaining one being a complex mutation. All eight T:A-targeted mutations were at 5'-TpA sites, hallmark mutations of PUVA mutagenesis. Through a rigorous statistical test, the PUVA-induced p53 mutation spectrum appears to differ significantly (P < 0.0002) from that observed in SCC in PUVA-treated patients. The present work demonstrates that a specific PUVA-induced mutational fingerprint could be obtained and recognized on human p53 cDNA. This result may suggest that PUVA therapy can be a risk factor for the development of SCC in psoriasis patients through a mechanism not involving the induction of p53 mutations.

DNA Mutational Analysis↗
PubMed1999

Platelet-dependent and procoagulant mechanisms in arterial thrombosis.

The results of experiment and clinical studies support the hypothesis that initiation and progression of arterial thrombosis are dependent on a dynamic interaction between platelet- and coagulation-dependent mechanisms. Although treatment of patients with unstable coronary syndromes acutely with glycoprotein IIb/IIIa inhibitors has already been shown to be remarkably effective in improving short- and long-term prognosis, strategies that inhibit factor thrombin and/or Xa activity may also have a role either alone or in combination with platelet inhibitors in treating patients with coronary thrombosis.

Anticoagulants↗
PubMed1998

Cutaneous mucinoses and HIV infection.

In the last few years cutaneous mucinoses have been reported with increased frequency in HIV patients. We report the occurrence of scleredema, reticular erythematous mucinosis and lichen myxoedematosus in three different HIV-infected patients, review the literature and discuss the possible relationship between mucin deposits and HIV infection. This is the first report of scleredema and the second of reticular erythematous mucinosis in an HIV-infected patient. Only the association of HIV infection with lichen myxoedematosus seems to be more than coincidental.

Adult↗
PubMed1998

Prolonged activation of prothrombin on the vascular wall after arterial injury.

This study was designed to characterize the relative roles of bound Xa/Va and thrombin activity in vascular wall procoagulant activity after balloon-induced injury and the extent to which intravenous aspirin and heparin attenuate procoagulant activity associated with the vascular wall. Abdominal aortic injury was induced in rabbits by overinflation and multiple passages ofa 4F embolectomy catheter. Rabbits were killed 15 minutes or 4, 8, 24, 48, 72, 96, or 120 hours after injury. Aortic segments were incubated ex vivo to define bound procoagulant activity. Thrombin activity bound to the aorta was detected by 4 hours after injury and was most marked over the first 24 hours, as estimated by increases in concentration of fibrinopeptide A during incubation of segments with recalcified barium-adsorbed plasma or activity against the thrombin-synthetic substrate S-2238. Based on comparison with purified human thrombin incubated under the same conditions, a maximum of 0.04 to 0.1 nmol/L per square centimeter of thrombin activity was associated with the vascular wall during the first 24 hours and remained detectable for 72 hours. In contrast, bound Xa/Va complex activity to injured segments was detected within 15 minutes and induced activation of prothrombin added to recalcified barium-adsorbed plasma incubated with injured segments for 96 hours. Aspirin (15 mg/kg) administered 30 minutes before injury attenuated 111In-platelet deposition at 4 hours by 67%, with an associated decrease in bound Xa/Va and thrombin activity at 15 minutes and 4 hours. However, intravenous heparin did not attenuate bound Xa/Va activity at 15 minutes or thrombin activity at 15 minutes and 4 hours. Platelet-dependent bound Xa/Va activity occurs rapidly after arterial injury and may promote thrombin elaboration for up to 96 hours. Bound thrombin activity and de novo thrombin elaboration on the vascular wall may play an important role in the progression of thrombosis and vascular wall remodeling.

Animals↗
PubMed1995

[Lichen planus and thymoma. A case].

INTRODUCTION: Lichen planus is a chronic inflammatory disease of the skin, rarely associated with a thymoma. CASE REPORT: A 72-year-old woman with erosive buccal lichen, hypertrophic lichen planus of the lower limbs, severe myasthenia and acquired hypogammaglobulinaemia associated with thymoma. CD8 lymphocyte count was increased. In the months following surgical ablation of the thymoma, the clinical examination and laboratory findings progressively returned to normal. Two years later, the patient was in good health. DISCUSSION: To our knowledge, this is the first report of favourable outcome after surgical treatment despite the aggressive symptomatology. The particular outcome allow confirmation that the thymoma plays a causal role in this syndrome and emphasizes the effects a thymoma can have on the immune system.

Agammaglobulinemia↗
PubMed1994

[Necrotizing vasculitis induced by cytomegalovirus in a woman with acquired immunodeficiency syndrome].

INTRODUCTION: Skin lesions induced by cytomegalovirus are rare and usually non-characteristic. CASE REPORT: A 32-year-old women with AIDS developed about twenty unpainful ulceronecrotic lesions on the extension aspect of the members and the trunk. Histology examination and in situ hybridization favoured cytomegalovirus infection of the skin. DISCUSSION: Despite the exceptional nature of this case, this particular clinical presentation should be recognized as it could be useful for early diagnosis of cytomegalovirus infection in immunodepressed subjects.

AIDS-Related Opportunistic Infections↗