Unbalanced metalloproteinase-9 and tissue inhibitors of metalloproteinases ratios predict hemorrhagic transformation of lesion in ischemic stroke patients treated with thrombolysis: Results from the MAGIC study

Background Experimentally, metalloproteinases (MMPs) play a detrimental role related to severity of ischemic brain lesions. Both MMPs activity and function in tissues reflect the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs). We aimed to evaluate the role of MMPs/TIMPs balance in the setting of rtPA treated stroke patients Methods Blood was taken before and 24-hours after rtPA from 327 patients (mean age 68 years, median NIHSS 11) with acute ischemic stroke. Delta median values of each MMP/TIMP ratio [(post rtPA MMP/TIMP-baseline MMP/TIMP)/(baseline MMP/TIMP)] were analyzed related to symptomatic intracranial hemorrhage (sICH) according to NINDS criteria, relevant hemorrhagic transformation (HT) defined as hemorrhagic infarction type 2 or any parenchimal hemorrhage, stroke subtypes (according to Oxfordshire Community Stroke Project) and 3-month death. The net effect of each MMP/TIMP ratio was estimated by a logistic regression model including major clinical determinants of outcomes Results Adjusting for major clinical determinants, only increase in MMP9/TIMP1 and MMP9/TIMP2 ratios remained significantly associated with sICH (odds ratio [95% confidence interval], 1.67 [1.17 – 2.38], p = 0.005; 1.74 [1.21 – 2.49], p=0.003 respectively). Only relative increase in MMP9/TIMP1 ratio proved significantly associated with relevant HT (odds ratio [95% confidence interval], 1.74 [1.17 – 2.57], p=0.006) with a trend towards significance for MMP9/TIMP2 ratio (p=0.007).Discussion Our data add substantial clinical evidence about the role of MMPs/TIMPs balance in rtPA treated stroke patients. These results may serve to generate hypotheses on MMPs inhibitors to be administered together with rtPA in order to counteract its deleterious effect

Improving the reporting quality of intervention trials addressing the inter-individual variability in response to the consumption of plant bioactives: quality index and recommendations

PURPOSE: The quality of the study design and data reporting in human trials dealing with the inter-individual variability in response to the consumption of plant bioactives is, in general, low. There is a lack of recommendations supporting the scientific community on this topic. This study aimed at developing a quality index to assist the assessment of the reporting quality of intervention trials addressing the inter-individual variability in response to plant bioactive consumption. Recommendations for better designing and reporting studies were discussed. METHODS: The selection of the parameters used for the development of the quality index was carried out in agreement with the scientific community through a survey. Parameters were defined, grouped into categories, and scored for different quality levels. The applicability of the scoring system was tested in terms of consistency and effort, and its validity was assessed by comparison with a simultaneous evaluation by experts' criteria. RESULTS: The "POSITIVe quality index" included 11 reporting criteria grouped into four categories (Statistics, Reporting, Data presentation, and Individual data availability). It was supported by detailed definitions and guidance for their scoring. The quality index score was tested, and the index demonstrated to be valid, reliable, and responsive. CONCLUSIONS: The evaluation of the reporting quality of studies addressing inter-individual variability in response to plant bioactives highlighted the aspects requiring major improvements. Specific tools and recommendations favoring a complete and transparent reporting on inter-individual variability have been provided to support the scientific community on this field

Guidelines for the use and interpretation of diagnostic methods in adult food allergy

Food allergy has an increasing prevalence in the general population and in Italy concerns 8 % of people with allergies. The spectrum of its clinical manifestations ranges from mild symptoms up to potentially fatal anaphylactic shock. A number of patients can be diagnosed easily by the use of first- and second-level procedures (history, skin tests and allergen specific IgE). Patients with complex presentation, such as multiple sensitizations and pollen-food syndromes, frequently require a third-level approach including molecular diagnostics, which enables the design of a component-resolved sensitization profile for each patient. The use of such techniques involves specialists' and experts' skills on the issue to appropriately meet the diagnostic and therapeutic needs of patients. Particularly, educational programs for allergists on the use and interpretation of molecular diagnostics are needed

Significance of F3/Contactin gene expression in cerebral cortex and nigrostriatal development

F3/Contactin is a neuronal surface glycoprotein, which plays a general role in neural development and, in particular, in neuronal and oligodendrocyte differentiation and in myelination. In previous studies using the F3/EGFP transgenic mice, which express an EGFP reporter under control of the regulatory region from the mouse F3/Contactin gene, the activation of the F3/Contactin promoter was found to correlate with granule and Purkinje neuron differentiation in developing cerebellar cortex. In this study we report that in developing cerebral cortex and basal ganglia the F3/Contactin gene is mostly activated during early commitment of neuronal precursors, thus indicating a region-specific profile of its developmental activation at the cellular level. We also report that, in the same structures of F3/EGFP mice, a downregulation of the endogenous F3/Contactin gene occurs, which correlates with upregulation of the dopaminergic phenotype and with locomotor pattern abnormalities. Therefore, F3/EGFP transgenic mice exhibit morphological and functional phenotypes recapitulating those arising from imbalance of the striatal dopaminergic pathway. As for the underlying mechanisms, we postulate that in F3/EGFP mice F3/Contactin downregulation results from the ability of transgene promoter sequences to interfere with the activation of the endogenous gene, thus realizing an F3/Contactin knockdown model, while dopaminergic upregulation is consistent with the general F3/Contactin inhibitory effects on the neuronal phenotype