123I-Interleukin-2 scintigraphy for the in vivo assessment of intestinal mononuclear cell infiltration in Chron's disease

Activated mononuclear cells expressing interleukin-2 (IL2) receptors (IL2-Rs) heavily infiltrate the Crohn’s disease (CD) gut wall. A new technique for the in vivo detection of tissue infiltrating IL2-R positive (IL2R1ve) cells was developed based on 123I-IL2 scintigraphy. The aim of this study was to investigate whether 123I-IL2 accumulates in the CD gut wall in different phases of the disease and to evaluate the specificity of 123I-IL2 binding to activated IL2R1ve cells infiltrating the gut wall. Methods: Fifteen patients with ileal CD (10 active and 5 inactive) and 10 healthy volunteers were studied by 123I-IL2 scintigraphy. Six patients with active CD were studied before and after 12 wk of steroid treatment. After scintigraphy, patients were followed up for 29–54 mo. Ex vivo autoradiography was performed to determine specificity of 125IIL2 binding to IL2R1ve cells. For bowel scintigraphy, 123I-IL2 (75 MBq) was injected intravenously and g camera images were acquired after 1 h. Bowel radioactivity was quantified in 64 regions of interest (ROIs). Results: Autoradiography showed specific binding of 125I-IL2 to IL2R1ve mononuclear cells infiltrating the CD gut wall. Intestinal 123I-IL2 uptake assessed by the number of positive ROIs was higher in patients with active or inactive CD than in healthy volunteers (P , 0.0001 andP 5 0.03, respectively) and positively correlated with the CD activity index (P 5 0.01). 123I-IL2 intestinal uptake significantly decreased in patients with CD in steroid-induced remission (P 5 0.03). A significant correlation was observed between the number of positive ROIs and time to disease relapse. Conclusion: 123I-IL2 accumulates in the diseased CD gut wall by specific binding to IL2R1ve cells, infiltrating the involved tissues. 123I-IL2 scintigraphy may be an objective tool for the in vivo assessment of intestinal activated mononuclear cell infiltration

A real world experience with fingolimod in active RRMS patients naïve to second-line agents: a 2 years, intention-to-treat, observational, single center study

Fingolimod is approved by EMA as a second-line treatment for relapsing-remitting multiple sclerosis (RRMS). Experience with fingolimod in real life is still limited. Aim of our study was to report data on fingolimod effectiveness in a real life cohort of Italian active RRMS patients, naive to second-line agents, followed for 2 years. Fingolimod was a part of the patients' regular treatment and is produced by Novartis. We included all consecutive RRMS patients starting fingolimod at our center according to EMA criteria before January 1st 2013. Exclusion criteria were a previous treatment with natalizumab or an immunosuppressant therapy in the previous 12 months. All patients were clinically evaluated quarterly, and performed brain MRI yearly. Definition of "no evidence of disease activity" (NEDA-3): no relapses, no brain MRI activity and no 6-months confirmed worsening in EDSS score. We included 38 RRMS patients, 35 switched from first-line injectable therapies. Six patients were also previously treated with immunosuppressants (5 mitoxantrone, 1 cyclophosphamide). At 24th month 34 patients continued fingolimod treatment. Main adverse events were infections (18 %), liver-enzymes elevation (8 %), and leukopenia (8 %). After 12 and 24 months 79 and 63 % of patients were relapses-free. Fingolimod significantly reduced ARR compared to the previous year (0.3 ± 0.6 vs 1.2 ± 0.5; p < 0.001). After 12 and 24 months 63 and 37 % of patients had NEDA-3. Previous use of immunosuppressants and an ARR ≥1 in the 2 years predicted disease activity. Fingolimod significantly reduce disease activity in active RRMS patients, with no severe/unexpected safety issues. Patients previously treated with immunosuppressants and with a higher ARR at baseline may respond less to fingolimod treatment

Experimental investigation of the impact of optical injection on vital parameters of a gain-switched pulse source

An analysis of optical injection on a gain-switched distributed feedback (DFB) laser and its impact on pulse parameters that influence the performance of the pulse source in high-speed optical communication systems is presented in this paper. A range of 10 GHz in detuning and 5 dB in injected power has been experimentally identified to attain pulses, from an optically injected gain-switched DFB laser, with durations below 10 ps and pedestal suppression higher than 35 dB. These pulse features are associated with a side mode suppression ratio of about 30 dB and a timing jitter of less than 1 ps. This demonstrates the feasibility of using optical injection in conjunction with appropriate pulse compression schemes for developing an optimized and cost-efficient pulse source, based on a gain-switched DFB laser, for high-speed photonic systems

Stability of the nonlinear dynamics of an optically injected VCSEL

Automated protocols have been developed to characterize time series data in terms of stability. These techniques are applied to the output power time series of an optically injected vertical cavity surface emitting laser (VCSEL) subject to varying injection strength and optical frequency detuning between master and slave lasers. Dynamic maps, generated from high resolution, computer controlled experiments, identify regions of dynamic instability in the parameter space. © 2012 Optical Society of America