Natalizumab in Multiple Sclerosis: Long-Term Management

Natalizumab is a monoclonal antibody highly effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients. Despite its effectiveness, there are growing concerns regarding the risk of progressive multifocal leukoencephalopathy (PML), a brain infection caused by John Cunningham virus (JCV), particularly after 24 doses and in patients who previously received immunosuppressive drugs. Long-term natalizumab treated, immunosuppressive-pretreated, and JCV antibody-positive patients are asked to rediscuss natalizumab continuation or withdrawal after 24 doses. Until now, there has not been a clear strategy that should be followed to avoid PML risk and in parallel reduce clinical and radiological rebound activity. In this review, we analyzed the results of clinical trials and case reports in relation to the following situations: natalizumab continuation, natalizumab discontinuation followed by full therapeutic suspension or switch to other first or second line MS treatments. Quitting all MS treatment after natalizumab increases MS activity occurrence. The results regarding the therapeutic switch are not homogeneous, so at the moment there are no established guidelines regarding natalizumab treatment after 24 administrations; the choice is currently based on the professional experience of the neurologist, and on patients’ clinical features and preferences

Relation between configurational entropy and relaxation dynamics of glass-forming systems under volume and temperature reduction

SUMMARY The structural relaxation dynamics of two molecular glass-forming systems have been analyzed by means of dielectric spectroscopy, under cooling and compression conditions. The relation of the dynamic slowing down with the reduction of the configurational entropy, SC, as predicted by Adam and Gibbs (AG), was also investigated. As SC is not directly accessible by experiments, it was estimated, following a common procedure in literature, from the excess entropy Sexc of the supercooled liquid with respect to the crystal, determined from calorimetric and expansivity measurements over the same T–P range of dynamics investigation. The AG relation, predicting linear dependence between the logarithmic of structural relaxation time and the reciprocal of the product of temperature with configurational entropy, was successfully tested. Actually, a bilinear relation between Sexc and SC was found, with different proportionality factors in isothermal and isobaric conditions. Using such results, we derived an equation for predicting the pressure dependence of the glass transition temperature, in good accordance with the experimental values in literature

UV-Curing of Acrylic Formulations by Means of Polymeric Photoinitiators with the Active 2,6-Dimethylbenzoylphosphine Oxide Moieties Pendant from a Tetramethylene Side Chain

Polymeric photoinitiators (PIs) bearing the 2,6-dimethylbenzoylphosphine oxide moiety pendant from flexible tetramethylene oxide side chains were synthesised by reacting their polymeric precursors, based on 4-(4'-acryloyloxy-1'-butoxy)-2,6-dimethylbenzoic acid (ABDBA), with diphenylmethylphosphinite. The resulting 4-(4'-acryloyloxy-1'-butoxy)-2,6-dimethylbenzoylphosphine oxide (ABDBPO) homo- and copolymers with butyl acrylate (BA), poly(ABDBPO) and poly(ABDBPO-co-BA), were employed in UV-curing experiments using model clear-coating (hexandiol diacrylate/butyl acrylate, HDDA/BA) and adhesive acrylic formulations. The photoinitiated radical polymerisations were followed by microwave dielectrometry, which allows real-time monitoring of the main kinetic parameters such as induction time, t(0), polymerisation rate, and absolute monomer conversion. The low molecular weight 2,4,6-trimethylbenzoylphospine oxide (TMBPO) and the couple ethyl 4-dimetllylaminobenzoate/isopropyl thioxantone (EPD/TTX) were also used as reference acylphosphine oxide (APO) and nonAPO PIs in parallel experiments. The kinetic data from the HDDA/BA system were compared with analogous literature data on acrylic PI with the APO moiety directly attached to the backbone. The presence of the flexible spacer does not significantly affect the initiation efficiency of the APO, whereas the initial viscosity of the medium resulting from the presence of macromer resins in the adhesive formulations markedly reduces both polymerisation rate and final conversion

Influence of molecular characteristics on dielectric relaxation of propylene glycol oligomers

The relaxation dynamics of polyropylene glycol oligomers having different end groups was studied by broadband dielectric spectroscopy (10 mHz to 10 GHz) in the temperature interval 110-350 K. above and below the glass transition. The effects produced on structural and secondary relaxations by the different end groups are discussed

Effect of water inclusions on charge transport and polarization in porous media

Wideband dielectric spectroscopy measurements (100 Hz to 10 GHz) were carried out on different microporous systems (including sintered glass filters, sandstone and carbonate rocks) saturated with brine (electrolytic water solution) and a hydrocarbon oil at different relative fractions. Three main contributions were singled out in the dielectric speetra: low frequency dispersion (LFD) effects (1 GHz) due to short-range ion transport and related to specific pore surface. For each analyzed system, oil-wet (o-w) and water-wet (w-w) samples were obtained by chemical treatment of the pore surfaces. Systematic differences were observed in the electrical response on varying wettability land so the respective distribution of the fluids in the pore space). Parameters such as the loss tangent value, the strength and the exponent of the LFD power law, as well as the characteristic time and strength of the MWS relaxation were good indicators of wettability. Results were discussed by using some standard models that account for the pore wettability effects on dielectric spectra. A new method for wettability determination of reservoir rocks from both laboratory and borehole electric measurements was presented

Fast formation of ripples induced by AFM. A new method for patterning polymers on nanoscale

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Effect of temperature and pressure on the structural (alpha-) and the true Johari-Goldstein (beta-) relaxation in binary mixtures

We investigated the microscopic origin of the excess wing through isothermal and isobaric dielectric relaxation measurements for the Quinaldine/tristyrene mixture. Our results show that the excess wing, characteristic of the high frequency side of the structural loss peak in neat Quinaldine, becomes a well resolved Johari-Goldstein secondary relaxation on mixing with the apolar tristyrene. Analyzing the temperature and pressure behavior of the two processes, a clear correlation has been found between the structural relaxation time, the Johari-Goldstein relaxation time and the dispersion of the structural relaxation (i.e. its Kohlrausch parameter). These results support the idea that the Johari-Goldstein relaxation acts as a precursor of the structural relaxation and therefore of the glass transition phenomenon. (c) 2007 Elsevier B.V. All rights reserved

The role of primitive relaxation in the dynamics of aqueous mixtures, nano-confined water and hydrated proteins RID A-8503-2012

The relaxation scenario in aqueous systems, such as mixtures of water with hydrophilic solutes, nano-confined water and hydrated biomolecules, has been shown to exhibit general features, in spite of the huge differences in structure, chemical composition and complexity. Dynamics, in all these systems, invariably shows at least two relaxations: (i) a slower process, related to cooperative and structural motions of water and solute molecules (in the case of mixtures) or related to interfacial processes in the case of confined water and (ii) a faster process, with non-cooperative character originating from water. The latter has properties including timescale and temperature dependence similar or related in all the aqueous systems. This water-specific relaxation can be identified as the primitive relaxation, or the Johari-Goldstein beta-relaxation. The primitive process is the precursor of the many-body relaxation process which increases in length-scale with time until the terminal a-relaxation is reached. Using new experimental data (at atmospheric and high pressure) along with a revision of most of the recent literature on the dynamics of confined water and aqueous mixtures, we show that the two abovementioned relaxation processes are inter-related as evidenced by correlations in their properties. For instance, both relaxation time and dielectric strength of the water-specific relaxation exhibit a crossover from a stronger to a weaker dependence with decreasing T, at the temperature where the slow process attains a very long timescale (>1 ks) and becomes structurally arrested, exactly analogous to that found for beta-relaxation in van der Waals liquids. Moreover, the primitive relaxation of water is shown to play a pivotal role in determining the dynamics of hydrated biomolecules in general, including the "dynamic transition" observed by neutron scattering and Mossbauer spectroscopy. We show that the primitive relaxation of the solvent is responsible for the dynamic transition, even in the case that the solvent is not pure water or an aqueous mixture. (C) 2010 Elsevier B.V. All rights reserved