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We compared the discriminatory capacity of the sequential organ failure assessment (SOFA) versus the systemic inflammatory response syndrome (SIRS) score for predicting ICU mortality, need for and length of mechanical ventilation, ICU stay, and hospitalization in patients with suspected infection admitted to a mixed Brazilian ICU. We performed a retrospective analysis of a longitudinal ICU database from a tertiary hospital in Southern Brazil. Patients were categorized according to whether they met the criteria for sepsis according to SOFA (variation ≥2 points over the baseline clinical condition) and SIRS (SIRS score ≥2 points). From January 2008 to December 2014, 1487 patients were admitted to the ICU due to suspected infection. SOFA ≥2 identified more septic patients than SIRS ≥2 (79.0% [n=1175] vs. 68.5% [n=1020], p<0.001). There was no difference between the two scores in predicting ICU mortality (area under the receiver operating characteristic curve (AUROC)=0.64 vs. 0.64, p=0.99). SOFA ≥2 was marginally better than SIRS ≥2 in predicting need for mechanical ventilation (AUROC=0.64 vs. 0.62, p=0.001), ICU stay>7 days (AUROC=0.65 vs. 0.63, p=0.004), and length of hospitalization >10 days (AUROC=0.61 vs. 0.59, p<0.001). There was no difference between the two scores in predicting mechanical ventilation >7 days., (Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

Background: Radiation therapy is routinely prescribed for high-grade malignant gliomas. However, the efficacy of this therapeutic modality is often limited by the occurrence of radioresistance, reflected as a diminished susceptibility of the irradiated cells to undergo cell death. Thus, cells have evolved an elegant system in response to ionizing radiation induced DNA damage, where p53, Hsp70 and/or EGFr may play an important role in the process. In the present study, we investigated whether the content of p53, Hsp70 and EGFr are associated to glioblastoma (GBM) cell radioresistance., Methods: Spheroids from U-87MG and MO59J cell lines as well as spheroids derived from primary culture of tumor tissue of one GBM patient (UGBM1) were irradiated (5, 10 and 20 Gy), their relative radioresistance were established and the p53, Hsp70 and EGFr contents were immunohistochemically determined. Moreover, we investigated whether EGFr-phospho-Akt and EGFr-MEK-ERK pathways can induce GBM radioresistance using inhibitors of activation of ERK (PD098059) and Akt (wortmannin)., Results: At 5 Gy irradiation UGBM1 and U-87MG spheroids showed growth inhibition whereas the MO59J spheroid was relatively radioresistant. Overall, no significant changes in p53 and Hsp70 expression were found following 5 Gy irradiation treatment in all spheroids studied. The only difference observed in Hsp70 content was the periphery distribution in MO59J spheroids. However, 5 Gy treatment induced a significant increase on the EGFr levels in MO59J spheroids. Furthermore, treatment with inhibitors of activation of ERK (PD098059) and Akt (wortmannin) leads to radiosensitization of MO59J spheroids., Conclusions: These results indicate that the PI3K-Akt and MEK-ERK pathways triggered by EGFr confer GBM radioresistance.

Accumulating evidences suggest that glutamate plays a key role in the proliferation and invasion of malignant glioblastoma (GBM) tumors. It has been shown that GBM cells release and exploit glutamate for proliferation and invasion through AMPA glutamate receptors. Additionally, amplification of the epidermal growth factor receptor (EGFR) gene occurs in 40-50% of GBM. Since, PI3K/Akt is considered one of the main intracellular pathways involved in EGFR activation, AKT functions could trigger EGFR signaling. Thus, we investigated whether EGFR-phospho-Akt pathway is involved on the glutamate inducing U-87MG human GBM cell line proliferation. For these purpose, we treated the U-87MG cell line with 5 to 200 mM of glutamate and assessed the number of viable cells by trypan blue dye exclusion test. An increase in cell number (50%) was found at 5 mM glutamate, while the addition of DNQX (500 microM), an antagonist of AMPA receptor, inhibited the effect of glutamate on the U87-MG cells proliferation. Also, at 5 mM glutamate we observed an increase on the EGFR and phospho-Akt contents evaluated by immunohistochemistry. Moreover, U-87MG cells treated with glutamate exhibited an increase about 2 times in the EGFR mRNA expression. While, in the presence of the anti-EGFR gefitinib (50 muM) or the PI3K inhibitor wortmannin (5 muM), the U-87MG proliferation was restored to control levels. Together, our data suggest that glutamate signaling mediated by AMPA receptor induces U-87MG human GBM cell line proliferation via EGFR-phospho-Akt pathway.

Background: We examined whether induction of apoptosis and Mn-superoxide dismutase (Mn-SOD) and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) activities were involved in the greater cytotoxicity of the irinotecan (CPT-11)/5-fluorouracil (5-FU) combination for human colon cancer cells when compared to both drugs alone., Methods: HT-29 and SNU-C4 human colon carcinoma cell lines were treated with 5-FU and CPT-11, then apoptosis was evaluated by flow cytometry and SOD activities were determined by polyacrylamide gel electrophoresis., Results: Enhanced apoptosis of HT-29 cells was observed with all treatments containing 5-FU in SNU-C4 cells; however, in HT-29 cells, apoptosis was enhanced only with the CPT-11/5-FU combination. In the SNU-C4 cell line, none of the treatments exerted a significant effect on Cu,Zn-SOD or Mn-SOD activity. However, in HT-29 cells, the CPT-11/5-FU combination enhanced Mn-SOD activity when compared to cells treated with CPT-11 alone. Nevertheless, the combined treatment did not interfere with Cu,Zn-SOD activity., Conclusion: Treatment with the CPT-11/5-FU combination may promote in HT-29 cell apoptosis by enhancing Mn-SOD activity., (Copyright 2005 S. Karger AG, Basel)

Recent research has implicated glutamate in the growth and invasive migration of gliomas. Superoxide dismutase (SOD) is involved in excitotoxicity and may influence cellular proliferative status. Thus, this study investigated the effects of gliotoxic doses of glutamate on Cu-Zn and Mn/SODs activities in human glioma cell lines. To this end, glioma cell lines (U87MG, U138MG and U251MG) were treated with glutamate (5-200 mM) during 48 h. Then, cell viability assays, clonogenic assay and Cu-Zn and Mn/SODs activities of the cell lines were performed. IC50values of glutamate were similar for both U87MG and U138MG cells (56 and 69 mM, respectively), while a higher value was detected for U251MG cells (110 mM). In the long term, 14 days after glutamate was removed from the culture media, cells showed partial or complete recovery. The effects of glutamate treatment on Cu-Zn and Mn/SODs activities varied among the distinct cell lines. While acute treatment with toxic doses of glutamate caused a significant decrease in the Cu-Zn/SOD activity of U138MG and U251MG cells, it did not affect Cu-Zn/SOD activity in U87MG cells. Only in U251MG cells, acute glutamate treatment decreased significantly Mn/SOD activity. In the long term (14 days after the 48 h treatment), glutamate did not affect either Cu-Zn or Mn/SODs activities. Thus, it may be suggested that SOD vulnerability to glutamate-mediated effects may be related to distinct tumoral cell behavior.