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A gelatinase-based device for fast detection of wound infection was developed. Collective gelatinolytic activity in infected wounds was 23 times higher (p ≤ 0.001) than in noninfected wounds and blisters according to the clinical and microbiological description of the wounds. Enzyme activities of critical wounds showed 12-fold elevated enzyme activities compared with noninfected wounds and blisters. Upon incubation of gelatin-based devices with infected wound fluids, an incubation time of 30 minutes led to a clearly visible dye release. A 32-fold color increase was measured after 60 minutes. Both matrix metalloproteinases and elastases contributed to collective gelatinolytic enzyme activity as shown by zymography and inhibition experiments. The metalloproteinase inhibitor 1,10-phenanthroline (targeting matrix metalloproteinases) and the serine protease inhibitor phenylmethlysulfonyl fluoride (targeting human neutrophil elastase) inhibited gelatinolytic activity in infected wound fluid samples by 11-37% and 60-95%, respectively. Staphylococcus aureus and Pseudomonas aeruginosa, both known for gelatinase production, were isolated in infected wound samples. © 2013 by the Wound Healing Society.

Glioblastoma cell resistance to chemotherapy is due mainly to the MDR efflux pump and to the impairment of DNA repair mechanisms such as MGMT and PARP1. Tumor stem cells are responsible for cell resistance. We studied in glioblastoma cell lines, neurospheres or adherent cells, the effects of two antiblastic[for full text, please go to the a.m. URL], 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

To evaluate MGMT promoter hypermethylation as prognostic factor in a retrospective study of 104 cases of glioblastoma multiforme (GBM).The O(6)-methylguanine-DNA methyltransferase (MGMT) status was evaluated by methylation-specific PCR (MSP), immunohistochemistry and Western blotting analysis in formalin-fixed paraffin-embedded surgical samples.The MGMT gene was found to be methylated in 29 of 101 tumors (28.7%) by MSP, according to the evaluation methods employed. By immunohistochemistry, different categories were identified on the basis of reaction intensity, percentage of positive cells and homogeneous or heterogeneous distribution. MSP did not correlate with immunohistochemistry, with the exception of the category with the highest percentage of positive cells and homogeneity of immunostaining. Western blotting analysis correlated with immunohistochemical findings (Pearson's correlation coefficient r=0.268, p=0.0211), but not with MSP. By Kaplan-Meier survival analysis, radiotherapy was a significant prognostic factor (p=0.0001). When uncensored patients alone were considered, MGMT methylation status showed a significant correlation with survival (p=0.026). Temozolomide therapy correlated with survival (p=0.022), but not with MGMT methylation. After multivariate Cox regression analysis, only radiotherapy remained as an independent prognostic factor (p=0.0001).Correlation was inconclusive among MSP, immunohistochemistry and Western blotting analysis, despite the sophisticated score system for the immunohistochemical quantitative evaluation. MGMT expression is a complex event in which many factors beside epigenetic silencing are implicated.

Proteasomes are multisubunit proteases involved in many cellular processes, including tumorigenesis and immune surveillance. In their catalytic core, the 20S proteasome, the beta1, beta2 and beta5 subunits show peptidylglutamyl peptide hydrolyzing (PGPH), trypsin-like and chymotrypsin-like activities, respectively. By IFN-gamma and TNFalpha stimulus, these subunits are replaced by their counterparts LMP2, MECL-1 and LMP7, defined inducible subunits, thus originating the immunoproteasome, and expression of the proteasome activator PA28 is enhanced. These modifications strengthen MHC-class I restricted peptide generation. The 20S proteasome has been detected immunohistochemically in formalin-fixed samples purified from fresh surgical specimens of 18 tumors (G20S) and from 8 samples of normal peritumoral tissue. The G20S, LMP2, MECL-1 and LMP7 increased in only 12 cases, along with unvaried trypsin-like and decreased PGPH and chymotrypsin-like activities; PA28 was unvaried in all 18 samples. The immunoproteasome alterations may represent an anomalous immunological attitude of glioblastomas.

The validity of discharge diagnosis of amyotrophic lateral sclerosis (ALS) and of the main procedures performed during hospitalization was assessed using as gold standard the data from the Piemonte and Valle d'Aosta Register for ALS (PARALS), a collaborative population-based registry aimed at determining prospectively the incidence and the factors related to ALS outcome. All patients discharged with ICD code 335.2 (primary and secondary diagnoses) in the period 1995-1996 in Piemonte, Italy, were considered. Out of the 1,049 cases identified, 433 remained after excluding patients not resident in Piemonte and repeated admissions. Of these, 258 had a correct diagnosis of ALS (168 incident and 90 prevalent cases) after a review of clinical records. The sensitivity of discharge diagnoses was 78.9%, and the positive predictive value was 38.8%. The sensitivity for main procedures (percutaneous endoscopic gastrostomy, noninvasive ventilation, and tracheostomy) ranged between 76 and 100%. ICD codes allowed to identify 22 cases that had not been ascertained with other sources. In conclusion, hospital discharge records appear to poorly reflect the incidence of ALS, and can be used only after clinical verification of the diagnosis.