Eligible were patients admitted for thrombolysis in 14 Italian centers and were registered in the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR), according to SITS-Monitoring Study criteria. 6 Study protocol was approved from each ethical committee, and all patients gave informed consent.Background and Purpose-Experimentally, matrix metalloproteinases (MMPs) play a detrimental role related to hemorrhagic transformation and severity of an ischemic brain lesion. Tissue-type plasminogen activator (tPA) enhances such effects. This study aimed to expand clinical evidence in this connection. Methods-We measured MMPs 1, 2, 3,7,8, 9, and Blood samples were taken before and 24 hours after tPA. Outcomes were defined as follows: (1) symptomatic intracerebral hemorrhage (SICH), using the National Institute of Neurological Disorders and Stroke criteria; 7 (2) 3-month death; (3) modified Rankin disability score, dichotomized into good (modified Rankin scale, 0-2) or poor (modified Rankin scale, 3-6) outcome. As a main explanatory variable, we used single patient's relative pre-and post-thrombolysis variation (Δ median value) of both MMPs and TIMPs levels, calculated according to the formula: (24-hour post-tPA MMP or TIMP-pre-tPA MMP or TIMP)/pre-tPA MMP or TIMP. Differences in these Δ values were analyzed in relation to demographic and clinical features and across subgroups of patients with different outcomes. Methods details are in the online-only Data Supplement. ResultsBetween October 2008 and June 2011, 534 patients were registered in the SITS-ISTR, of whom 327 (mean age, 68.9±12.1 years; 58% males) were investigated. The remaining 207 were not studied because of not fulfilling SITS-MOST criteria, not giving consent, blood samples not taken or not stored appropriately, outcomes not assessed, and other protocol violations. Except for onset-to-treatment time, the prevalence of major outcomes determinants did not differ significantly between the 2 groups (demographics and clinical characteristics of both groups are in Table I in the online-only Data Supplement).Absolute TIMPs or MMPs measures taken before thrombolysis and 24 hours after are reported in the Table II in the online-only Data Supplement.The Figure shows pre-and post-thrombolysis changes of each MMP and TIMP level measured in patients with and without SICH, in patients who died and in those who survived, and in patients scoring 3 to 6 or 0 to 2 on the 3-month modified Rankin scale. MMP9, TIMP4, and MMP2 level changes showed a tendency toward the association with SICH. Variations of MMP8, MMP9, and TIMP1 levels were significantly associated with death, whereas variations of MMP8, MMP9, and TIMP4 levels were associated with scoring 3 to 6 on the 3-month modified Rankin scale. Grading of hemorrhage severity (according to the European Cooperative Acute Stroke Study II criteria) in the 27 patients with SICH is shown in Table III in the online-only Data Supplement. The association of MMP9 level variation with he...

Background and Purpose-The beneficial effect of intravenous thrombolytic therapy in patients with acute ischemic stroke attributable to internal carotid artery (ICA) occlusion remains unclear. The aim of this study was to evaluate the efficacy and safety of intravenous recombinant tissue-type plasminogen activator in these patients. Methods-ICARO was a case-control multicenter study on prospectively collected data. Patients with acute ischemic stroke and ICA occlusion treated with intravenous recombinant tissue-type plasminogen activator within 4.5 hours from symptom onset (cases) were compared to matched patients with acute stroke and ICA occlusion not treated with recombinant tissue-type plasminogen activator (controls). Cases and controls were matched for age, gender, and stroke

The enhancement of bacterial resistance of pathogens to currently available antibiotics constitutes a serious public health threat. So, intensive efforts are underway worldwide to develop new antimicrobial agents. To identify compounds with a potent antimicrobial profile, we designed and synthesized low molecular weight 2-mercaptobenzothiazole derivatives 2a-2l and 3a-3l. Both series were screened for in-vitro antibacterial activity against the representative panel of Gram-positive and Gram-negative bacteria strains. The biological screening identified compounds 2e and 2l as the most active ones showing an interesting antibacterial activity with MIC values of 3.12 microg/mL against Staphylococcus aureus and 25 microg/mL against Escherichia coli, respectively. The replacement of the S-H by the S-Bn moiety resulted in considerable loss of the antibacterial action of the 3a-3l series. The antibiotic action of compounds 2e and 2l was also investigated by testing their activity against some clinical isolates with different antimicrobial resistance profile. Moreover, the involvement of the NorA efflux pump in the antibacterial activity of our molecules was evaluated. Finally, in this paper, we also describe the cytotoxic activity of the most interesting compounds by MTS assay against HeLa and MRC-5 cell lines.

Inflammatory mediators and metalloproteinases are altered in acute ischemic stroke (AIS) and play a detrimental effect on clinical severity and hemorrhagic transformation of the ischemic brain lesion. Using data from the Italian multicenter observational MAGIC (MArker bioloGici nell'Ictus Cerebrale) Study, we evaluated the effect of inflammatory and metalloproteinases profiles on three-month functional outcome, hemorrhagic transformation and mortality in 327 patients with AIS treated with intravenous thrombolys in according to SITS-MOST (Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy) criteria. Circulating biomarkers were assessed at baseline and 24 h after thrombolysis. Adjusting for age, sex, baseline glycemia and National Institute of Health Stroke Scale, history of atrial fibrillation or congestive heart failure, and of inflammatory diseases or infections, baseline alpha-2macroglobulin (A2M), baseline serum amyloid protein (SAP) and pre-post tissue-plasminogen activator (tPA) variations (Δ) of metalloproteinase 9, remained significantly and independently associated with three-month death [OR (95% CI):A2M:2.99 (1.19-7.53); SAP:5.46 (1.64-18.74); Δmetalloproteinase 9:1.60 (1.12-2.27)]. The addition of baseline A2M and Δmetalloproteinase 9 or baseline SAP and Δmetalloproteinase 9 (model-2 or model-3) to clinical variables (model-1) significantly improved the area under curve for prediction of death [model-2 with A2M: p = 0.0205; model-3 with SAP: p = 0.001]. In conclusion, among AIS patients treated with thrombolysis, circulating A2M, SAP and Δmetalloproteinase 9 are independent markers of poor outcome. These results may prompt controlled clinical research about agents antagonizing their effect.