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1.
Aliment Pharmacol Ther ; 46(4): 424-431, 2017 08.
Article in English | MEDLINE | ID: mdl-28660640

ABSTRACT

BACKGROUND: Patients with thalassaemia major depend on blood transfusions. In Italy, up to 80% of thalassaemia patients bear HCV antibodies due to HCV contaminated transfusions before 1990. Thalassaemia patients with HCV infection have high risk of developing HCC. Treatment based on Pegylated-IFN (Peg-IFN) and Ribavirin (RBV) was limited by relevant side effects. AIM: To evaluate the impact of Sofosbuvir/Ledipasvir (SOF/LDV) fixed dose combination for 12 weeks without RBV, in patients with thalassaemia major and HCV Genotype 1 or 4 (GT1/4). METHODS: Open label, historically-controlled, nationwide multicentre study in thalassaemia patients including naïve with cirrhosis and prior treatment failure without cirrhosis. SOF/LDV single pill was administered for 12 weeks to 100 patients of whom 16% had cirrhosis. The control group included 96 patients with comparable baseline characteristics treated with Peg-IFN/RBV. The primary end point was sustained virologic response at follow-up week 12 or 24 after IFN-free or Peg-IFN/RBV, respectively. RESULTS: In the study group, sustained virological response (SVR) was reported in 98% of patients (95% CI 95.3%-100%). Cirrhotic as well as prior treatment failure achieved 100% SVR. In the control group, SVR was 47.9% (95% CI 37.9%-57.9%). Adverse events including fatigue, headache, nausea, decrease in haemoglobin or increase in ferritin levels were rare and significantly less common in the study than in the historical control group. CONCLUSIONS: In conclusion, SOF/LDV for 12 weeks provides simple, highly effective and safe Peg-IFN/RBV-free treatment for HCV GT1/4 thalassaemia patients. EUDRACT number 2015-002401-1.


Subject(s)
Benzimidazoles/therapeutic use , Fluorenes/therapeutic use , Hepatitis C, Chronic/drug therapy , Thalassemia , Uridine Monophosphate/analogs & derivatives , Adult , Antiviral Agents/therapeutic use , Drug Therapy, Combination , Female , Genotype , Hepacivirus/genetics , Humans , Italy , Liver Cirrhosis/drug therapy , Male , Middle Aged , Ribavirin/therapeutic use , Sofosbuvir , Treatment Failure , Uridine Monophosphate/therapeutic use
2.
Nanoscale ; 8(17): 9293-303, 2016 Apr 28.
Article in English | MEDLINE | ID: mdl-27088757

ABSTRACT

Electrospinning is a versatile method for preparing functional three-dimensional scaffolds. Synthetic and natural polymers have been used to produce micro- and nanofibers that mimic extracellular matrices. Here, we describe the use of emulsion electrospinning to prepare blended fibers capable of hosting aqueous species and releasing them in solution. The existence of an aqueous and a non-aqueous phase allows water-soluble molecules to be introduced without altering the structure and the degradation of the fibers, and means that their release properties under physiological conditions can be controlled. To demonstrate the loading capability and flexibility of the blend, various species were introduced, from magnetic nanoparticles and quantum rods to biological molecules. Cellular studies showed the spontaneous adhesion and alignment of cells along the fibers. Finally, in vivo experiments demonstrated the high biocompatibility and safety of the scaffolds up to 21 days post-implantation.


Subject(s)
Biocompatible Materials , Tissue Engineering , Tissue Scaffolds , Cell Line, Tumor , Emulsions , Humans , Nanofibers , Polymers
3.
Methods Mol Biol ; 1025: 179-98, 2013.
Article in English | MEDLINE | ID: mdl-23918338

ABSTRACT

The cryosectioning technique is an alternative method for preparing biological material for Transmission Electron Microscopy (TEM). We have applied this technique to study the mechanism of cell internalization of stimuli-responsive polymeric nanogels exploited as cargo nanovectors. With respect to conventional TEM processing, cryosectioning technique better preserves the morphology of solvent-sensitive nanogels and enhances the visibility of membrane-bounded organelles inside the cell cytoplasm. In this chapter we describe the protocols we have established to perform Electron Microscopy (EM)-immunocytochemistry, Electron Tomography (ET), and Energy Dispersive X-ray Spectroscopy (EDXS) chemical analysis in Scanning TEM (STEM) on cryosections of HeLa cells treated with pH-responsive nanogels hosting short interference RNA (siRNAs) and iron oxide nanoparticles (IONPs).


Subject(s)
Cryoultramicrotomy/methods , Ferric Compounds/metabolism , HeLa Cells/metabolism , Nanoparticles/metabolism , Polyethylene Glycols/metabolism , Polyethyleneimine/metabolism , Polymers/metabolism , RNA Interference/physiology , Electron Microscope Tomography , HeLa Cells/ultrastructure , Humans , Immunohistochemistry , Microscopy, Electron, Transmission , Molecular Biology/methods , Nanogels , Polyethylene Glycols/chemistry , Polyethyleneimine/chemistry , Spectrometry, X-Ray Emission
4.
Acta Haematol ; 125(4): 219-21, 2011.
Article in English | MEDLINE | ID: mdl-21266801

ABSTRACT

Iron overload sometimes complicates the clinical course of bone marrow transplantation and can cause damage to liver and heart function. A patient with post-transplantation secondary hemochromatosis was treated with deferasirox, which not only normalized ferritin levels, but also reduced hepatic iron to normal values as measured by biosusceptometry with a superconducting quantum interference device. Side effects were minimal. The use of deferasirox to reduce post-transplant iron burden merits evaluation in a larger patient population.


Subject(s)
Anemia, Aplastic/complications , Benzoates/therapeutic use , Hemochromatosis/drug therapy , Triazoles/therapeutic use , Adult , Anemia, Aplastic/therapy , Bone Marrow Transplantation/adverse effects , Deferasirox , Ferritins/blood , Hemochromatosis/etiology , Humans , Iron/metabolism , Iron Chelating Agents/therapeutic use , Iron Overload/drug therapy , Male
5.
Plant Biol (Stuttg) ; 13(1): 51-8, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21143725

ABSTRACT

Artemisia annua L. is a herb traditionally used for treatment of fevers. The glandular trichomes of this plant accumulate, although at low levels, artemisinin, which is highly effective against malaria. Due to the great importance of this compound, many efforts have been made to improve knowledge on artemisinin production both in plants and in cell cultures. In this study, A. annua suspension cultures were established in order to investigate the effects of methyl jasmonate (MeJA) and miconazole on artemisinin biosynthesis. Twenty-two micro molar MeJA induced a three-fold increase of artemisinin production in around 30 min; while 200 µm miconazole induced a 2.5-fold increase of artemisinin production after 24 h, but had severe effects on cell viability. The influence of these treatments on expression of biosynthetic genes was also investigated. MeJA induced up-regulation of CYP71AV1, while miconazole induced up-regulation of CPR and DBR2.


Subject(s)
Acetates/pharmacology , Artemisia annua/drug effects , Artemisia annua/metabolism , Artemisinins/metabolism , Cyclopentanes/pharmacology , Gene Expression Regulation, Plant/drug effects , Miconazole/pharmacology , Oxylipins/pharmacology , Artemisia annua/cytology , Artemisia annua/genetics , Artemisinins/chemistry , Cell Survival/drug effects , Cells, Cultured , Molecular Structure , RNA, Messenger/biosynthesis
6.
Rev Sci Instrum ; 81(11): 111301, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21133454

ABSTRACT

The electric solar wind sail (E-sail) is a space propulsion concept that uses the natural solar wind dynamic pressure for producing spacecraft thrust. In its baseline form, the E-sail consists of a number of long, thin, conducting, and centrifugally stretched tethers, which are kept in a high positive potential by an onboard electron gun. The concept gains its efficiency from the fact that the effective sail area, i.e., the potential structure of the tethers, can be millions of times larger than the physical area of the thin tethers wires, which offsets the fact that the dynamic pressure of the solar wind is very weak. Indeed, according to the most recent published estimates, an E-sail of 1 N thrust and 100 kg mass could be built in the rather near future, providing a revolutionary level of propulsive performance (specific acceleration) for travel in the solar system. Here we give a review of the ongoing technical development work of the E-sail, covering tether construction, overall mechanical design alternatives, guidance and navigation strategies, and dynamical and orbital simulations.

7.
Food Addit Contam ; 22(4): 309-15, 2005 Apr.
Article in English | MEDLINE | ID: mdl-16019800

ABSTRACT

Fusarium trichothecenes are a group of fungal toxic metabolites whose synthesis requires the action of gene products from three different genetic loci. We evaluated, both chemically and by PCR assays, 55 isolates of Fusarium culmorum from eight European countries and different host plants for their ability to produce trichothecenes. Specific sequences in the Tri6-Tri5 intergenic region were associated with deoxynivalenol production. Sequences in the Tri3 gene were also associated with deoxynivalenol production and specific primer sets were selected from these sequences to identify 3-acetyl-deoxynivalenol or 15-acetyl-deoxynivalenol chemotypes. Specific sequences in the Tri5 and Tri7 genes were associated with the nivalenol chemotype but not with the deoxynivalenol chemotype. Two chemotypes were identified by chemical analysis and confirmed by PCR. Strains of the nivalenol chemotype produced nivalenol (up to 260 microg g(-1)) and 4-acetyl-nivalenol (up to 60 microg g(-1)), strains with the 3-acetyl-deoxynivalenol chemotype produced deoxynivalenol (up to 1700 microg g(-1)) and 3-acetyl-deoxynivalenol (up to 600 microg g(-1)). Three strains of F. culmorum from France, previously reported as 15-acetyl-deoxynivalenol producers, had the 3-acetyl-deoxynivalenol chemotype. The results are consistent with data from other European countries on the occurrence of the nivalenol and 3-acetyl-deoxynivalenol chemotypes and provide support for the hypothesis that European isolates of F. culmorum producing deoxynivalenol belong only to the 3-acetyl-deoxynivalenol chemotype. The production of trichothecenes from F. culmorum isolates from walnut (3-acetyl-deoxynivalenol chemotype) and leek (nivalenol chemotype) is reported for the first time.


Subject(s)
Food Microbiology , Fusarium/classification , Trichothecenes/biosynthesis , DNA, Fungal/genetics , Europe , Fusarium/genetics , Fusarium/metabolism , Genes, Fungal , Mycological Typing Techniques/methods , Mycoses/microbiology , Plant Diseases/microbiology , Polymerase Chain Reaction/methods , Triticum/microbiology
8.
Minerva Ginecol ; 41(7): 371-3, 1989 Jul.
Article in Italian | MEDLINE | ID: mdl-2608206

ABSTRACT

The technique used for immediate repair of a delivery-induced vesico-urethral lesion is described.


Subject(s)
Obstetric Labor Complications , Urethra/injuries , Urinary Bladder/injuries , Adult , Female , Humans , Pregnancy
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