Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats

Experimental autoimmune encephalomyelitis (EAE) is mediated by CD4+ Th1 cells that mainly secrete IFN-γ and TNF-α, important cytokines in the pathophysiology of the disease. Spontaneous remission is, in part, attributed to the down regulation of IFN-γ and TNF-α by TGF-β. In the current paper, we compared weight, histopathology and immunological parameters during the acute and recovery phases of EAE to establish the best biomarker for clinical remission. Female Lewis rats were immunised with myelin basic protein (MBP) emulsified with complete Freund's adjuvant. Animals were evaluated daily for clinical score and weight prior to euthanisation. All immunised animals developed the expected characteristics of EAE during the acute phase, including significant weight loss and high clinical scores. Disease remission was associated with a significant reduction in clinical scores, although immunised rats did not regain their initial weight values. Brain inflammatory infiltrates were higher during the acute phase. During the remission phase, anti-myelin antibody levels increased, whereas TNF-α and IFN-γ production by lymph node cells cultured with MBP or concanavalin A, respectively, decreased. The most significant difference observed between the acute and recovery phases was in the induction of TNF-α levels in MBP-stimulated cultures. Therefore, the in vitro production of this cytokine could be used as a biomarker for EAE remission

Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids

We report here the design, development and performance of a novel formulation of liposome- encapsulated glucocorticoids (GCs). A highly efficient (>90%) and stable GC encapsulation was obtained based on a transmembrane calcium acetate gradient driving the active accumulation of an amphipathic weak acid GC pro-drug into the intraliposome aqueous compartment, where it forms a GC-calcium precipitate. We demonstrate fabrication principles that derive from the physicochemical properties of the GC and the liposomal lipids, which play a crucial role in GC release rate and kinetics. These principles allow fabrication of formulations that exhibit either a fast, second-order (t1/2 ∼1 h), or a slow, zero-order release rate (t1/2 ∼ 50 h) kinetics. A high therapeutic efficacy was found in murine models of experimental autoimmune encephalomyelitis (EAE) and hematological malignancies

An international collaborative evaluation of central serous chorioretinopathy: different therapeutic approaches and review of literature. The European Vitreoretinal Society central serous chorioretinopathy study

Purpose: To study and compare the efficacy of different therapeutic options for the treatment of central serous chorioretinopathy (CSCR). Methods: This is a nonrandomized, international multicentre study on 1719 patients (1861 eyes) diagnosed with CSCR, from 63 centres (24 countries). Reported data included different methods of treatment and both results of diagnostic examinations [fluorescein angiography and/or optical coherent tomography (OCT)] and best-corrected visual acuity (BCVA) before and after therapy. The duration of observation had a mean of 11 months but was extended in a minority of cases up to 7 years. The aim of this study is to evaluate the efficacy of the different therapeutic options of CSCR in terms of both visual (BCVA) and anatomic (OCT) improvement. Results: One thousand seven hundred nineteen patients (1861 eyes) diagnosed with CSCR were included. Treatments performed were nonsteroidal anti-inflammatory eye drops, laser photocoagulation, micropulse diode laser photocoagulation, photodynamic therapy (PDT; Standard PDT, Reduced-dose PDT, Reduced-fluence PDT), intravitreal (IVT) antivascular endothelial growth factor injection (VEGF), observation and other treatments. The list of the OTHERS included both combinations of the main proposed treatments or a variety of other treatments such as eplerenone, spironolactone, acetazolamide, beta-blockers, anti-anxiety drugs, aspirin, folic acid, methotrexate, statins, vitis vinifera extract medication and pars plana vitrectomy. The majority of the patients were men with a prevalence of 77%. The odds ratio (OR) showed a partial or complete resolution of fluid on OCT with any treatment as compared with observation. In univariate analysis, the anatomical result (improvement in subretinal fluid using OCT at 1 month) was favoured by age <60 years (p < 0.005), no previous observation (p < 0.0002), duration less than 3 months (p < 0.0001), absence of CSCR in the fellow eye (p = 0.04), leakage outside of the arcade (p = 0.05) and fluid height >500 \u3bcm (p = 0.03). The OR for obtaining partial or complete resolution showed that anti-VEGF and eyedrops were not statistically significant; whereas PDT (8.5), thermal laser (11.3) and micropulse laser (8.9) lead to better anatomical results with less variability. In univariate analysis, the functional result at 1 month was favoured by first episode (p = 0.04), height of subretinal fluid >500 \u3bcm (p < 0.0001) and short duration of observation (p = 0.02). Finally, there was no statistically significant difference among the treatments at 12 months. Conclusion: Spontaneous resolution has been described in a high percentage of patients. Laser (micropulse and thermal) and PDT seem to lead to significant early anatomical improvement; however, there is little change beyond the first month of treatment. The real visual benefit needs further clarification

Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Supported by F. Hoffmann–La Roche