Delocalized Nature of the E'-delta Center in Amorphous Silicon Dioxide

We report an experimetal study by Electron Paramagnetic Resonance (EPR) of E'-delta point defect induced by gamma ray irradiation in amorphous SiO2. We obtained an estimetion of the intensity of the 10 mT doublet characterizing the EPR spectrum of such a defect arising from hyperfine interaction of the unpaired electron with a 29Si (I=1/2) nucleus. Moreover, determining the intensity ratio between this hyperfine doublet and the main resonance line of E'-delta center, we pointed out that unpaired electron wave function of this center is actually delocalized over four nearly equivalent silicon atoms.Comment: approved for publication in Physical Review Letter

Increased IL-6 and IL-4 in exhaled breath condensate of patients with nasal polyposis.

Abstract BACKGROUND AND AIM: Nasal polyposis (NP) occurs in about 1-4% of the worldwide population. Increased plasma concentrations of different pro-inflammatory cytokines have been observed in NP, and might be related to the pathogenesis of this syndrome. The present study was designed to investigate IL-6 and IL-4 concentrations in nasal and oral exhaled breath condensate of patients with early and advanced NP, and following polypectomy. METHODS: Ten individuals with polyposis in early status, twenty-three patients affected by advanced status of NP and ten healthy controls were enrolled into the study. Exhaled breath condensate was collected by all individuals, according to a previous standardised method. An immunoassay kit was used to measure IL-6 and IL-4 levels. RESULTS: Concentrations of oral and nasal exhaled IL-6 and IL-4 were significantly higher in patients with early nasal polyposis and advanced nasal polyposis, compared to healthy controls. A statistically significant decrease of nasally but not of orally exhaled IL-6 (p < 0.001) and IL-4 (p < 0.05) was observed after polypectomy. CONCLUSIONS: We consider oral and nasal exhaled condensate of IL-6 and IL-4 as valid inflammatory and oxidative stress marker in patients with nasal polyposis

Structural relaxation of E' gamma centers in amorphous silica

We report experimental evidence of the existence of two variants of the E' gamma centers induced in silica by gamma rays at room temperature. The two variants are distinguishable by the fine features of their line shapes in paramagnetic resonance spectra. These features suggest that the two E' gamma differ for their topology. We find a thermally induced interconversion between the centers with an activation energy of about 34 meV. Hints are also found for the existence of a structural configuration of minimum energy and of a metastable state.Comment: 4 pages, 2 figures, submitted to Phys. Rev. Let

Increased IL-6 and IL-4 in exhaled breath condensate of patients with nasal polyposis

Background and Aim. Nasal polyposis (NP) occurs in about 1-4% of the worldwide population. Increased plasma concentrations of different pro-inflammatory cytokines have been observed in NP, and might be related to the pathogenesis of this syndrome.The present study was designed to investigate IL-6 and IL-4 concentrations in nasal and oral exhaled breath condensate of patients with early and advanced NP, and following polypectomy. Methods. Ten individuals with polyposis in early status, twenty-three patients affected by advanced status of NP and ten healthy controls were enrolled into the study. Exhaled breath condensate was collected by all individuals, according to a previous standardised method. An immunoassay kit was used to measure IL-6 and IL-4 levels. Results. Concentrations of oral and nasal exhaled IL- 6 and IL-4 were significantly higher in patients with early nasal polyposis and advanced nasal polyposis, compared to healthy controls. A statistically significant decrease of nasally but not of orally exhaled IL-6 (p<0.001) and IL-4 (p<0.05) was observed after polypectomy. Conclusions. We consider oral and nasal exhaled condensate of IL-6 and IL-4 as valid inflammatory and oxidative stress marker in patients with nasal polyposis

Enzastaurin inhibits tumours sensitive and resistant to anti-EGFR drugs

We investigated the antitumour effect and ability to overcome the resistance to anti-EGFR drugs of enzastaurin, an inhibitor of VEGFR-dependent PKCβ signalling. Enzastaurin was evaluated alone and in combination with the EGFR inhibitor gefitinib, on growth and signalling protein expression in human cancer cells sensitive and resistant to anti-EGFR drugs, both in vitro and in nude mice. We demonstrated the marked inhibitory activity of enzastaurin against GEO colon and PC3 prostate cancer cells and their gefitinib-resistant counterparts GEO-GR and PC3-GR, accompanied by inhibition of pAkt and its effector pp70S6K, pGSK3β and VEGF expression and secretion. Moreover, enzastaurin showed a cooperative effect with gefitinib in parental and in gefitinib-resistant cells. Remarkably, these results were confirmed in vivo, where enzastaurin showed antitumour activity and cooperativity with gefitinib in mice grafted with GEO and GEO-GR tumours, incrementing their median survival and inhibiting the aforesaid protein expression and secretion in tumour specimens. In conclusion, enzastaurin by interfering with signalling proteins implicated in EGFR drug resistance markedly cooperates with gefitinib in sensitive and gefitinib-resistant tumours, thus overcoming and reverting such resistance and providing a rational basis for its development in patients resistant to anti-EGFR drugs

A novel fully human antitumour immunoRNase targeting ErbB2-positive tumours

BACKGROUND: ErbB2 is an attractive target for immunotherapy, as it is a tyrosine kinase receptor overexpressed on tumour cells of different origin, with a key role in the development of malignancy. Trastuzumab, the only humanised anti-ErbB2 antibody currently used in breast cancer with success, can engender cardiotoxicity and a high fraction of patients is resistant to Trastuzumab treatment. METHODS: A novel human immunoRNase, called anti-ErbB2 human compact antibody-RNase (Erb-hcAb-RNase), made up of the compact anti-ErbB2 antibody Erbicin-human-compact Antibody (Erb-hcAb) and human pancreatic RNase (HP-RNase), has been designed, expressed in mammalian cell cultures and purified. The immunoRNase was then characterised as an enzymatic protein, and tested for its biological actions in vitro and in vivo on ErbB2-positive tumour cells. RESULTS: Erb-hcAb-RNase retains the enzymatic activity of HP-RNase and specifically binds to ErbB2-positive cells with an affinity comparable with that of the parental Erb-hcAb. Moreover, this novel immunoRNase is endowed with an effective and selective antiproliferative action for ErbB2-positive tumour cells both in vitro and in vivo. Its antitumour activity is more potent than that of the parental Erb-hcAb as the novel immunoconjugate has acquired RNase-based cytotoxicity in addition to the inhibitory growth effects, antibody-dependent and complement-dependent cytotoxicity of Erb-hcAb. CONCLUSION: Erb-hcAb-RNase could be a promising candidate for the immunotherapy of ErbB2-positive tumours