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Bozzo C.,University of Piemonte Orientale | Tiberio R.,Azienda Ospedaliero Universitaria Maggiore della Carita | Graziola F.,University of Piemonte Orientale | Pertusi G.,University of Piemonte Orientale | And 4 more authors.
Microbes and Infection | Year: 2010

The pathogenicity of Mycobacterium ulcerans (Buruli ulcer) depends on cytotoxic effect of its exotoxin mycolactone. Since epidermis represents a barrier against infectious agents and balanced apoptosis is essential in epidermal homeostasis, we explored if mycolactone A/B induces apoptosis on two human keratinocyte populations, stem cells (KSC) and transit amplifying cells (TAC), and on human keratinocyte line, HaCaT. Treatment of TAC with 1 and 10 ng/ml mycolactone-induced 60 and 90% apoptosis. KSC were more resistant than TAC: 50 and 75% of cells underwent apoptosis after 10 and 100 ng/ml toxin-treatment. Higher doses (1000 ng/ml) induced about 30% apoptosis on HaCaT. In contrast, mycolactone A/B was devoid of toxicity neither on human hepatoma HuH7 nor on human embryonic kidney HEK 293 T cell lines. In conclusion, mycolactone induces apoptosis in human keratinocytes, thus contributing to Buruli ulcer lesions development. © 2010 Institut Pasteur.


De Nunzio C.,University of Rome La Sapienza | Cindolo L.,Ospedale Padre Pio da Pietrelcina | Leonardo C.,University of Rome La Sapienza | Antonelli A.,University of Brescia | And 27 more authors.
European Journal of Surgical Oncology | Year: 2013

Introduction Standardized methods of reporting complications after radical cystectomy (RC) and urinary diversions (UD) are necessary to evaluate the morbidity associated with this operation to evaluate the modified Clavien classification system (CCS) in grading perioperative complications of RC and UD in a real life cohort of patients with bladder cancer. Materials and methods A consecutive series of patients treated with RC and UD from April 2011 to March 2012 at 19 centers in Italy was evaluated. Complications were recorded according to the modified CCS. Results were presented as complication rates per grade. Univariate and binary logistic regression analysis were used for statistical analysis. Results Results and limitations: 467 patients were enrolled. Median age was 70 years (range 35-89). UD consisted in orthotopic neobladder in 112 patients, ileal conduit in 217 patients and cutaneous ureterostomy in 138 patients. 415 complications were observed in 302 patients and were classified as Clavien type I (109 patients) or II (220 patients); Clavien type IIIa (45 patients), IIIb (22 patients); IV (11 patients) and V (8 patients). Patients with cutaneous ureterostomy presented a lower rate (8%) of CCS type ≥IIIa (p = 0.03). A longer operative time was an independent risk factor of CCS ≥III (OR: 1.005; CI: 1.002-1.007 per minute; p = 0.0001). Conclusions In our study, RC is associated with a significant morbidity (65%) and a reduced mortality (1.7%) when compared to previous experiences. The modified CCS represents an easily applicable tool to classify the complications of RC and UD in a more objective and detailed way. © 2013 Elsevier Ltd. All rights reserved.


Sutti S.,Health Science University | Rigamonti C.,Azienda Ospedaliero Universitaria Maggiore della Carita | Vidali M.,Azienda Ospedaliero Universitaria Maggiore della Carita | Albano E.,Health Science University
Redox Biology | Year: 2014

Autoimmune reactions involving cytochrome P4502E1 (CYP2E1) are a feature of idiosyncratic liver injury induced by halogenated hydrocarbons and isoniazid, but are also detectable in about one third of the patients with advanced alcoholic liver disease (ALD) and chronic hepatitis C (CHC). In these latter the presence of anti-CYP2E1 auto-antibodies is an independent predictor of extensive necro-inflammation and fibrosis and worsens the recurrence of hepatitis following liver transplantation, indicating that CYP2E1-directed autoimmunity can contribute to hepatic injury. The molecular characterization of the antigens recognized by anti-CYP2E1 auto-antibodies in ALD and CHC has shown that the targeted conformational epitopes are located in close proximity on the molecular surface. Furthermore, these epitopes can be recognized on CYP2E1 expressed on hepatocyte plasma membranes where they can trigger antibody-mediated cytotoxicity. This does not exclude that T cell-mediated responses against CYP2E1 might also be involved in causing hepatocyte damage. CYP2E1 structural modifications by reactive metabolites and molecular mimicry represent important factors in the breaking of self-tolerance against CYP2E1 in, respectively, ALD and CHC. However, genetic or acquired interferences with the mechanisms controlling the homeostasis of the immune system are also likely to contribute. More studies are needed to better characterize the impact of anti-CYP2E1 autoimmunity in liver diseases particularly in relation to the fact that common metabolic alterations such as obesity and diabetes stimulates hepatic CYP2E1 expression. © 2014.


Cavallo M.,University of Piemonte Orientale | Andreoni S.,Azienda Ospedaliero Universitaria Maggiore della Carita | Martinotti M.G.,University of Piemonte Orientale | Rinaldi M.,University of Piemonte Orientale | Fracchia L.,University of Piemonte Orientale
Mycopathologia | Year: 2013

The opportunistic pathogens belonging to the Aspergillus genus are present in almost all seasons of the year, and their concentration is related to meteorological conditions. The high density of Aspergillus spp. conidia in a haematological hospital ward may be a significant risk factor for developing invasive fungal diseases in immunocompromised patients. Aim of the present study was to evaluate the variability of airborne Aspergillus spp. conidia contamination in a Haematological Unit (HU) within a period of 16 months in relation with some meteorological parameters. An environmental Aspergillus surveillance was conducted in the HU in four rooms and their bathrooms, in the corridor and in three external sites using an agar impact sampler. During each sampling, temperature and relative humidity at each site were recorded and current wind speed and rainfall events were taken from the official weather service. Aspergillus spp. conidia concentration differed significantly across the sampling sites. Internal Aspergillus spp. loads were significantly dependent on temperature, internal relative humidity and rain. External conidia concentrations were significantly influenced by outdoor temperature and relative humidity. A suitable indicator was introduced to evaluate the seasonal distribution of Aspergillus spp. conidia in the sampling sites, and a significant dependence on this indicator was observed inside the HU. Seventeen different fungal species belonging to the Aspergillus genus were detected during the sampling period. Aspergillus fumigatus was the most frequently isolated species and its distribution depended significantly on the seasonal indicator both inside and outside the hospital ward. © 2013 Springer Science+Business Media Dordrecht.


Matheoud R.,Azienda Ospedaliero Universitaria Maggiore della Carita | Goertzen A.L.,University of Manitoba | Vigna L.,Azienda Ospedaliero Universitaria Maggiore della Carita | Ducharme J.,Great West Life Imaging Center | And 2 more authors.
Physica Medica | Year: 2012

PET scanners require routine monitoring and quality control (QC) to ensure proper scanner performance. QC helps to ensure that PET equipment performs as specified by the manufacturer and that there have not been significant changes in the system response since acceptance. In this work we describe the maintenance history and we report on the results obtained from the PET system QC testing program over 5 years at two centers, both utilizing a Siemens Biograph 16 HiRez PET/CT system. QC testing programs were based on international standards and included the manufacturer's daily QC, monthly uniformity and sensitivity, quarterly cross-calibration and annual resolution and image quality.For the Winnipeg and Novara sites, two and one PET detector blocks have been replaced, respectively. Neither system has had other significant PET system related hardware replacements. The manufacturer's suggested daily QC was sensitive to detecting problems in the function of PET detector elements. The same test was not sensitive for detecting long term drifts in the systems: the Novara system observed a significant deterioration over five years of testing in the sensitivity which exhibited a decrease of 16% as compared to its initial value measured at system installation. The measure of the energy spectrum, showed that the 511. keV photopeak had shifted to a position of 468. keV. This shift was corrected by having service personnel perform a complete system calibration and detector block setup.We recommend including tests of system energy response and of sensitivity as part of a QC program since they can provide useful information on the actual performance of the scanner. A modification of the daily QC test by the manufacturer is suggested to monitor the long term stability of the system. Image quality and spatial resolution tests have proven to be of limited value for monitoring the system over time. © 2011 Associazione Italiana di Fisica Medica.

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