15 research outputs found
Vaginal Lactoferrin Modulates PGE 2
Inflammation plays an important role in pregnancy, and cytokine and matrix metalloproteases (MMPs) imbalance has been associated with premature rupture of membranes and increased risk of preterm delivery. Previous studies have demonstrated that lactoferrin (LF), an iron-binding protein with anti-inflammatory properties, is able to decrease amniotic fluid (AF) levels of IL-6. Therefore, we aimed to evaluate the effect of vaginal LF administration on amniotic fluid PGE2 level and MMP-TIMP system in women undergoing genetic amniocentesis. One hundred and eleven women were randomly divided into controls (n = 57) or treated with LF 4 hours before amniocentesis (n = 54). Amniotic fluid PGE2, active MMP-9 and MMP-2, and TIMP-1 and TIMP-2 concentrations were determined by commercially available assays and the values were normalized by AF creatinine concentration. PGE2, active MMP-9, and its inhibitor TIMP-1 were lower in LF-treated group than in controls (p < 0.01, p < 0.005, and p < 0.001, resp.). Conversely, active MMP-2 (p < 0.0001) and MMP-2/TIMP-2 molar ratio (p < 0.001) were increased, whilst TIMP-2 was unchanged. Our data suggest that LF administration is able to modulate the inflammatory response following amniocentesis, which may counteract cytokine and prostanoid imbalance that leads to abortion. This trial is registered with Clinical Trial number NCT02695563
Treatment with recombinant tissue plasminogen activator (r-TPA) induces neutrophil degranulation in vitro via defined pathways.
AbstractThrombolysis is recommended for reperfusion following acute ischemic stroke (AIS), but its effects on stroke-associated injury remain to be clarified. Here, we investigated the effects of recombinant tissue plasminogen activator (r-tPA) on neutrophil pathophysiology in vitro and in a case–control study with AIS patients submitted (n=60) or not (n=30) to thrombolysis. Patients underwent radiological and clinical examination as well as blood sampling at admission and after 1, 7 and 90days. In vitro, 30-min incubation with 0.1–1mg/ml r-tPA induced neutrophil degranulation in different substrate cultures. Pre-incubation with kinase inhibitors and Western blot documented that degranulation was associated with activation of PI3K/Akt and ERK1/2 pathways in Teflon dishes and PI3K/Akt in polystyrene. In thrombolysed patients, a peak of neutrophil degranulation products (matrix metalloproteinase [MMP]-9, MMP-8, neutrophil elastase and myeloperoxidase), was shown during the first hours from drug administration. This was accompanied by serum augmentation of protective tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. An increased rate of haemorrhagic transformations on day 1 after AIS was shown in thrombolysed patients as compared to non-thrombolysed controls. In conclusion, r-tPA treatment was associated with in vitro neutrophil degranulation, indicating these cells as potential determinants in early haemorrhagic complications after thrombolysis in AIS patients
Fast skeletal troponin i, but not the slow isoform, is increased in patients under statin therapy: A pilot study
open9noCodice progetto: GR-2013-023555391Introduction: Statin therapy is often associated with muscle complaints and increased serum creatine kinase (CK). However, although essential in determining muscle damage, this marker is not specific for skeletal muscle. Recent studies on animal models have shown that slow and fast isoforms of skeletal troponin I (ssTnI and fsTnI, respectively) can be useful markers of skeletal muscle injury. The aim of this study was to evaluate the utility of ssTnI and fsTnI as markers to monitor the statin-induced skeletal muscle damage. Materials and methods: A total of 51 patients (14 using and 37 not using statins) admitted to the intensive care unit of the University of Ferrara Academic Hospital were included in this observational study. Serum activities of CK, aldolase, alanine aminotransferase and myoglobin were determined by spectrophotometric assays or routine laboratory analysis. Isoforms ssTnI and fsTnI were determined by commercially available ELISAs. The creatine kinase MB isoform (CK-MB) and cardiac troponin I (cTnI) were evaluated as biomarkers of cardiac muscle damage by automatic analysers. Results: Among the non-specific markers, only CK was significantly higher in statin users (P = 0.027). Isoform fsTnI, but not ssTnI, was specifically increased in those patients using statins (P = 0.009) evidencing the major susceptibility of fast-twitch fibres towards statins. Sub-clinical increase in fsTnI, but not CK, was more frequent in statin users (P = 0.007). Cardiac markers were not significantly altered by statins confirming the selectivity of the effect on skeletal muscle. Conclusions: Serum fsTnI could be a good marker for monitoring statin-associated muscular damage outperforming traditional markers.openTrentini, Alessandro; Spadaro, Savino; Rosta, Valentina; Manfrinato, Maria C; Cervellati, Carlo; Dalla Corte, Francesca; Hanau, Stefania; Volta, Carlo A; Bellini, TizianaTrentini, Alessandro; Spadaro, Savino; Rosta, Valentina; Manfrinato, Maria C; Cervellati, Carlo; Dalla Corte, Francesca; Hanau, Stefania; Volta, Carlo A; Bellini, Tizian
Clustering XML Documents using Self-Organizing Maps for Structures
Self-Organizing Maps capable of encoding structured information
will be used for the clustering of XML documents. Documents formatted in XML
are appropriately represented as graph data structures. It will be shown that the
Self-Organizing Maps can be trained in an unsupervised fashion to group XML
structured data into clusters, and that this task is scaled in linear time with in-
creasing size of the corpus. It will also be shown that some simple prior knowl-
edge of the data structures is beneficial to the efficient grouping of the XML
documents
Metabolic characterisation of transglutaminase 2 inhibitor effects in breast cancer cell lines
Transglutaminase 2 (TG2), which mediates post-translational modifications of multiple intracellular enzymes, is involved in the pathogenesis and progression of cancer. We used H-1-NMR metabolomics to study the effects of AA9, a novel TG2 inhibitor, on two breast cancer cell lines with distinct phenotypes, MCF-7 and MDA-MB-231. AA9 can promote apoptosis in both cell lines, but it is particularly effective in MD-MB-231, inhibiting transamidation reactions and decreasing cell migration and invasiveness. This metabolomics study provides evidence of a major effect of AA9 on MDA-MB-231 cells, impacting glutamate and aspartate metabolism, rather than on MCF-7 cells, characterised by choline and O-phosphocholine decrease. Interestingly, AA9 treatment induces myo-inositol alteration in both cell lines, indicating action on phosphatidylinositol metabolism, likely modulated by the G protein activity of TG2 on phospholipase C. Considering the metabolic deregulations that characterise various breast cancer subtypes, the existence of a metabolic pathway affected by AA9 further points to TG2 as a promising hot spot. The metabolomics approach provides a powerful tool to monitor the effectiveness of inhibitors and better understand the role of TG2 in cancer
TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in patients with multiple sclerosis
Background: The activity of matrix metalloproteinase-9 (MMP-9) depends on two isoforms, an 82 kDa active MMP-9 modulated by its specific tissue inhibitor (TIMP-1), and a 65 kDa TIMP-1 resistant active MMP-9. The relevance of these two enzymatic isoforms in multiple sclerosis (MS) is still unknown. Objective: To investigate the contribution of the TIMP-1 modulated and resistant active MMP-9 iso-forms to MS pathogenesis. Methods: We measured the serum levels of the 82 kDa and TIMP-1 resistant active MMP-9 isoforms by activity assay systems in 86 relapsing-remitting MS (RRMS) patients, categorized according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, and in 70 inflammatory (OIND) and 69 non-inflammatory (NIND) controls. Results: Serum levels of TIMP-1 resistant MMP-9 were more elevated in MS patients than in OIND and NIND (p < 0.05, p < 0.02, respectively). Conversely, 82 kDa active MMP-9 was higher in NIND than in the OIND and MS patients (p < 0.01 and p < 0.00001, respectively). MRI-active patients had higher levels of TIMP-1 resistant MMP-9 and 82 kDa active MMP-9, than did those with MRI inactive MS (p < 0.01 and p < 0.05, respectively). Conclusion: Our findings suggested that the TIMP-1 resistant MMP-9 seem to be the predominantly active isoform contributing to MS disease activity