A revolution in stroke therapy: reperfusion therapy effective even if late

Arterial recanalization procedures after ischaemic stroke, are now well-established treatments, within 5 h for systemic thrombolysis, and 6 h for the endovascular treatment. Ischaemic stroke with uncertain time of symptoms onset, account for 14-27% of the cases, the vast majority of which occur just after waking up, thus it is impossible to derive an exact timeline. Accordingly, these patients are frequently not eligible for acute treatment. The results of three recent trials, DAWN, DEFUSE 3, and WAKE-UP, provided the basis for a revolution in the selection of patients eligible for late revascularization, and revealed an increase in the rate of functional independence for these patients at 90 days (mRS 0-2). Advanced neuroimaging techniques have been shown to be of utmost importance in the definition of the cerebral tissue window. A wider application of these imaging techniques and standardization of the parameters of images acquisition would provide for a significant advancement in the management of ischaemic stroke in the emergency setting

Time is brain: timing of revascularization of brain arteries in stroke

Ischaemic stroke is the second leading cause of mortality and disability in the western world. Revascularization interventions are the cornerstone of the acute treatment of this pathology and must be administered as soon as possible after the patient's arrival. They consist of intravenous thrombolysis (IVT) with alteplase, recommended by the guidelines within 4.5 h of the onset of symptoms, and endovascular treatment, recommended within 6 h of the onset of symptoms. The individualized patient selection based on the extent of the mismatch between the penumbra and the ischaemic core allowed to overcome the limits imposed by the rigid time windows, defining a benefit of mechanical revascularization therapies up to 24 h from the theoretical onset of symptoms (last time the patient was known to be well) and up to 9 h for IVT since the theoretical onset of symptoms (last time the patient was known to be well). Advanced neuroimaging methods with perfusion studies are a fundamental tool in patient selection. Their spread in the territory, together with a greater availability of neurovascular treatment units are desirable to ensure a fair delivery of treatment to all patients with ischaemic stroke

POSTERIOR CIRCULATION STROKE PRESENTING AS A BOW HUNTER’S SYNDROME:WHEN A DYNAMIC APPROACH IS NEEDED

Background and Aims: Posterior circulation stroke cause detection represents a diagnostic challenge in emergency. Vertebral artery (VA) dissection is a frequent cause in young patients. Methods: We describe two cases of posterior circulation stroke, both related to VA dissection, in which ultrasound evaluation with dynamic study, was fundamental for diagnosis. Results: Case 1: 38 yrs old man admitted at the ER for acute onset of severe neck pain, headache, objective vertigo, nausea. Cerebral MRI showed left cerebellum ischemic lesion. Ultrasound revealed right V2 vertebral artery dissection with intramural hematoma and distal poststenotic flow, that was less identifiable with angioTC. Case 2: 44 yrs old man admitted at the ER for neck pain, vertigo and left limb paresthesias after head rotation while parking the car in reverse gear. Cerebral MRI showed a left cerebellum ischemic lesion. Both MR and CT angiographies failed to identify vertebral artery dissection. At ultrasound, flow stop in the left VA, only during right neck rotation, was detected while performing transcranial imaging through subnucal approach. Angio-CTwith right head rotation confirmed the vertebral artery occlusion at C1-C2 level, without disc herniation or osteophytes. This findings support a Rotational Vertebral Artery Occlusion syndrome with ischemic stroke (Bow Hunter’s stroke), probably due to left VA dissection at V3. Conclusions: Accurate ultrasound evaluation of posterior circulation, eventually with dynamic manouvers, have to be considered in the diagnostic work-up of posterior circulation strokes. Bow Hunter’s syndrome is a rare cause of vertebrobasilar insufficiency and could be underdiagnosed in clinical practice

Direct synthesis of C3-mono-functionalized oxindoles from N-unprotected 2-oxindole and their antileishmanial activity

A novel approach for the synthesis of unprecedented C3-mono-functionalized indolin-2-ones is reported, starting from 2-oxindole and chalcones. The reactions proceed regioselectively under mild conditions, without di- and tri-alkylated side products. The new compounds have been evaluated in vitro for their antiproliferative effects against the protozoan Leishmania infantum. Interestingly, they appear able to kill L. infantum promastigotes and amastigotes, without significant cytotoxic effects

Role of Factor V R2 Haplotype and Common Thrombophilia Markers as Genetic Risk Factors for Ischemic Stroke

Uncertainties remain about the role of common thrombophilia markers as determinants of the ischemic stroke (IS) risk. Polymorphism His1299Arg in the FV gene, named R2 haplotype (FVHR2), has been poorly investigated. The aim of the present study was to assess the prevalence of common thrombophilia markers and of FVHR2 in a cohort of IS patients compared to a nonmatched group of healthy individuals

Role of Factor V R2 Haplotype and Common Thrombophilia Markers as Genetic Risk Factors for Ischemic Stroke

Uncertainties remain about the role of common thrombophilia markers as determinants of the ischemic stroke (IS) risk. Polymorphism His1299Arg in the FV gene, named R2 haplotype (FVHR2), has been poorly investigated. The aim of the present study was to assess the prevalence of common thrombophilia markers and of FVHR2 in a cohort of IS patients compared to a nonmatched group of healthy individuals

Synthesis of C3/C1-Substituted Tetrahydroisoquinolines

A broad biological screening of the natural alkaloid N-methylisosalsoline (2) extracted from Hammada scoparia leaves against a panel of human and parasitic proteases revealed an interesting activity profile of 2 towards human 20S proteasome. This outcome suggests that the 1,2,3,4-tetrahydroisoquinoline skeleton may be exploited as a template for the development of novel anticancer agents. In this article, we report the synthesis and chemical characterization of a new series of isosalsoline-type alkaloids (10–11) with variations at N2 and C3 positions with respect to the natural Compound 2, obtained by a synthetic strategy that involves the Bischler-Napieralski cyclization. The substrate for the condensation to the tetrahydroisoquinoline system, i.e., a functionalized β-arylethyl amine, was obtained through an original double reduction of nitroalkene. The synthetic strategy can be directed to the construction of highly substituted and functionalized 1,2,3,4-tetrahydroisoquinolines

Self-Catalyzed Mannich-Type Reaction of Enolizable Cyclic 1,3-Dicarbonyls to Acyclic Nitrones: An Entry to Functionalized β‑Enamino Diones

A new method for the preparation of highly functionalized β-enamino diones has been developed. The protocol involves an initial self-catalyzed Mannich-type reaction of enolizable cyclic 1,3-dicarbonyls to nitrones, followed by a spontaneous intramolecular reorganization of the resulting nonisolated hydroxylamine to enamino derivatives. These compounds retain the features of unnatural α-amino acids. The ease of preparation makes them attractive intermediates for the synthesis of peptidomimetics, polyheterocycles, and other multifunctional compounds. All experimental results have been efficiently rationalized by in silico studies at the M06-2X level of theory, and a valid mechanistic pathway has been proposed

Factor H interferes with the adhesion of sickle red cells to vascular endothelium : a novel disease-modulating molecule

Sickle cell disease is an autosomal recessive genetic red cell disorder with a worldwide distribution. Growing evidence suggests a possible involvement of complement activation in the severity of clinical complications of sickle cell disease. In this study we found activation of the alternative complement pathway with microvascular deposition of C5b-9 on skin biopsies from patients with sickle cell disease. There was also deposition of C3b on sickle red cell membranes, which is promoted locally by the exposure of phosphatidylserine. In addition, we showed for the first time a peculiar "stop-and-go" motion of sickle cell red blood cells on tumor factor-alpha-activated vascular endothelial surfaces. Using the C3b/iC3b binding plasma protein factor H as an inhibitor of C3b cell-cell interactions, we found that factor H and its domains 19-20 prevent the adhesion of sickle red cells to the endothelium, normalizing speed transition times of red cells. We documented that factor H acts by preventing the adhesion of sickle red cells to P-selectin and/or the Mac-1 receptor (CD11b/CD18), supporting the activation of the alternative pathway of complement as an additional mechanism in the pathogenesis of acute sickle cell related vaso-occlusive crises. Our data provide a rationale for further investigation of the potential contribution of factor H and other modulators of the alternative complement pathway with potential implications for the treatment of sickle cell disease.Peer reviewe