Salt and ionic cocrystalline forms of amides: protonation of carbamazepine in aqueous media

The products of reactions of the pharmaceutical amide carbamazepine (CBZ) with strong acids under aqueous conditions were investigated by both powder and single crystal X-ray diffraction. Despite previous claims to the contrary, it was found that salt forms with CBZ protonated at the amide O atom could be isolated from reactions with both HCl and HBr. These forms include the newly identified hydrate phase [CBZ(H)][Cl]·H O. Reactions with other mineral acids (HI and HBF ) gave ionic cocrystalline (ICC) forms (CBZ· [acridinium][I ]·2.5I and CBZ·[H O ] [BF ] ·H O) as well as the salt form CBZ·[CBZ(H)][BF ]·0.5H O. Reaction 2 4 3 2 5 2 0.25 4 0.25 2 4 2 of CBZ with a series of sulfonic acids also gave salt forms, namely, [CBZ(H)][O SC H ], [CBZ(H)][O SC H (OH)]· 3 6 5 3 6 4 0.5H O, [CBZ(H)] [O SCH CH SO ], and [CBZ(H)][O SC H (OH) (COOH)]·H O. CBZ and protonated CBZ(H) 2 2 3 2 2 3 3 6 3 2 moieties can be differentiated in the solid state both by changes to molecular geometry and by differing packing preference

Arago (1810): the first experimental result against the ether

95 years before Special Relativity was born, Arago attempted to detect the absolute motion of the Earth by measuring the deflection of starlight passing through a prism fixed to the Earth. The null result of this experiment gave rise to the Fresnel's hypothesis of an ether partly dragged by a moving substance. In the context of Einstein's Relativity, the sole frame which is privileged in Arago's experiment is the proper frame of the prism, and the null result only says that Snell's law is valid in that frame. We revisit the history of this premature first evidence against the ether theory and calculate the Fresnel's dragging coefficient by applying the Huygens' construction in the frame of the prism. We expose the dissimilar treatment received by the ray and the wave front as an unavoidable consequence of the classical notions of space and time.Comment: 16 pages. To appear in European Journal of Physic

Calcitonin gene-related peptide promotes cellular changes in trigeminal neurons and glia implicated in peripheral and central sensitization

<p>Abstract</p> <p>Background</p> <p>Calcitonin gene-related peptide (CGRP), a neuropeptide released from trigeminal nerves, is implicated in the underlying pathology of temporomandibular joint disorder (TMD). Elevated levels of CGRP in the joint capsule correlate with inflammation and pain. CGRP mediates neurogenic inflammation in peripheral tissues by increasing blood flow, recruiting immune cells, and activating sensory neurons. The goal of this study was to investigate the capability of CGRP to promote peripheral and central sensitization in a model of TMD.</p> <p>Results</p> <p>Temporal changes in protein expression in trigeminal ganglia and spinal trigeminal nucleus were determined by immunohistochemistry following injection of CGRP in the temporomandibular joint (TMJ) capsule of male Sprague-Dawley rats. CGRP stimulated expression of the active forms of the MAP kinases p38 and ERK, and PKA in trigeminal ganglia at 2 and 24 hours. CGRP also caused a sustained increase in the expression of c-Fos neurons in the spinal trigeminal nucleus. In contrast, levels of P2X₃in spinal neurons were only significantly elevated at 2 hours in response to CGRP. In addition, CGRP stimulated expression of GFAP in astrocytes and OX-42 in microglia at 2 and 24 hours post injection.</p> <p>Conclusions</p> <p>Our results demonstrate that an elevated level of CGRP in the joint, which is associated with TMD, stimulate neuronal and glial expression of proteins implicated in the development of peripheral and central sensitization. Based on our findings, we propose that inhibition of CGRP-mediated activation of trigeminal neurons and glial cells with selective non-peptide CGRP receptor antagonists would be beneficial in the treatment of TMD.</p

Signals for Lorentz Violation in Electrodynamics

An investigation is performed of the Lorentz-violating electrodynamics extracted from the renormalizable sector of the general Lorentz- and CPT-violating standard-model extension. Among the unconventional properties of radiation arising from Lorentz violation is birefringence of the vacuum. Limits on the dispersion of light produced by galactic and extragalactic objects provide bounds of 3 x 10^{-16} on certain coefficients for Lorentz violation in the photon sector. The comparative spectral polarimetry of light from cosmologically distant sources yields stringent constraints of 2 x 10^{-32}. All remaining coefficients in the photon sector are measurable in high-sensitivity tests involving cavity-stabilized oscillators. Experimental configurations in Earth- and space-based laboratories are considered that involve optical or microwave cavities and that could be implemented using existing technology.Comment: 23 pages REVTe

Rietveld-based quantitative phase analysis of sugars in confectionery

Sugars are a near-ubiquitous ingredient in food products, yet rising rates of obesity and related illnesses have prompted a drive to reduce their content. The use of amorphous sugars in confectionery may be one way of achieving this by providing a similarly sweet sensation due to increased dissolution rate. However, accurate amorphous and crystalline form characterisation and quantification of complex foodstuffs can be difficult. In this study, a method for the quantification of crystalline and amorphous sugars in chocolate precursors, using powder X ray powder diffraction, is presented. The method was first validated by the use of known compositions of mixtures of amorphous and crystalline sugars, then employed in assessing two chocolate crumb samples. The results show that the method can reliably determine the absolute quantity of amorphous and crystalline components in a confectionery sample, whilst maintaining sample integrity, apart from the addition of an inert internal standard. As such, it is a valuable addition to other techniques currently used

Property enhancement of healable supramolecular polyurethanes

Low molecular weight additives which can cooperatively self-assemble with supramolecular polyurethanes via complementary hydrogen bonding interactions offer an attractive route to enhancing the properties of addressable polymer networks. Here, we present the design, synthesis, characterisation and mechanical properties of a series of supramolecular polyurethanes with varied loadings of a low molecular weight bis-urea additive. These additives are able to self-assemble with analogous recognition motifs within the supramolecular polyurethanes to form polar ‘hard’ domains, promoting phase separation within the material and, crucially, increasing the strength of the polymer network. In addition, the bis-urea additive is a by-product within the polymerisation and thus can be synthesised in situ, without the need for complex purification or blending. The mechanical properties of these reinforced polymers were enhanced when compared to the pristine supramolecular polyurethane alone, as a result of higher degrees of order within the polymer matrix. Furthermore, a formulation comprising the small molecule blended with the supramolecular polyurethane was produced to examine the effect of material preparation and filler dispersion within the polymer matrix. Interestingly, the mechanical performance of a blended material was diminished as a result of modest dispersion and incorporation within the polymer matrix. These findings thus demonstrate a facile, one-pot, method that does not require purification to produce reinforced supramolecular polyurethanes. This methodology may find use in industrial applications in which enhancements to the physical and mechanical properties can be easily achieved through the in situ synthesis of low molecular weight additives within the polymerisation

On the Search For Transits of the Planets Orbiting Gl 876

We report the results of a globally coordinated photometric campaign to search for transits by the P ~ 30 d and P ~ 60 d outer planets of the 3-planet system orbiting the nearby M-dwarf Gl 876. These two planets experience strong mutual perturbations, which necessitate use of a dynamical (four-body) model to compute transit ephemerides for the system. Our photometric data have been collected from published archival sources, as well as from our photometric campaigns that were targeted to specific transit predictions. Our analysis indicates that transits by planet "c" (P ~ 30 d) do not currently occur, in concordance with the best-fit i = 50 degree co-planar configuration obtained by dynamical fits to the most recent radial velocity data for the system. Transits by planet "b" (P ~ 60 d) are not entirely ruled out by our observations, but our data indicate that it is very unlikely that they occur. Our experience with the Gl 876 system suggests that a distributed ground-based network of small telescopes can be used to search for transits of very low mass M-stars by terrestrial-sized planets.Comment: currently 17pp w/Figs, 10 figures; to appear in Astrophysical Journal article December 2006 v653n

The NTI-tss device for the therapy of bruxism, temporomandibular disorders, and headache – Where do we stand? A qualitative systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>The NTI-tss device is an anterior bite stop, which, according to the manufacturer, is indicated for the prevention and treatment of bruxism, temporomandibular disorders (TMDs), tension-type headaches, and migraine. The aim of this systematic review was to appraise the currently available evidence regarding the efficacy and safety of the NTI-tss splint.</p> <p>Methods</p> <p>We performed a systematic search in nine electronic databases and in NTI-tss-associated websites (last update: December 31, 2007). The reference lists of all relevant articles were perused. Five levels of scientific quality were distinguished. Reporting quality of articles about randomized controlled trials (RCTs) was evaluated using the Jadad score. To identify adverse events, we searched in the identified publications and in the MAUDE database.</p> <p>Results</p> <p>Nine of 68 relevant publications reported about the results of five different RCTs. Two RCTs concentrated on electromyographic (EMG) investigations in patients with TMDs and concomitant bruxism (Baad-Hansen et al 2007, Jadad score: 4) or with bruxism alone (Kavaklı 2006, Jadad score: 2); in both studies, compared to an occlusal stabilization splint the NTI-tss device showed significant reduction of EMG activity. Two RCTs focused exclusively on TMD patients; in one trial (Magnusson et al 2004, Jadad score: 3), a stabilization appliance led to greater improvement than an NTI-tss device, while in the other study (Jokstad et al 2005, Jadad score: 5) no difference was found. In one RCT (Shankland 2002, Jadad score: 1), patients with tension-type headache or migraine responded more favorably to the NTI-tss splint than to a bleaching tray. NTI-tss-induced complications related predominantly to single teeth or to the occlusion.</p> <p>Conclusion</p> <p>Evidence from RCTs suggests that the NTI-tss device may be successfully used for the management of bruxism and TMDs. However, to avoid potential unwanted effects, it should be chosen only if certain a patient will be compliant with follow-up appointments. The NTI-tss bite splint may be justified when a reduction of jaw closer muscle activity (e.g., jaw clenching or tooth grinding) is desired, or as an emergency device in patients with acute temporomandibular pain and, possibly, restricted jaw opening.</p

Maintenance and refurbishment planning for a group of bridges

During the service, highway overpasses are exposed to various deterioration processes. The rate of these unavoidable processes depends on intensity of usage, weather influences and maintenance level. If maintenance works are not planned and executed in an adequate manner, the performance of the structures under consideration reduces. Planning an optimum set of intervention measures on the level of a group of structures is a complex task that is often left to subjective, partial decisions of managers that have to take int the account also financial limitations.\ud A group of 27 highway overpasses, spanning over the highway section under consideration, was analysed. A multi-criteria model for the selection of bridges that should have priority in the refurbishment process was developed. Condition rating data were collected from the periodic check\ud reports and and structured appropriately. Key criteria that need to be taken into the account were identified: condition ration of the whole structure, age of the pass, possibility of joining the works on a string of passes, indirect cost influence, refurbishment cost for a structure and deterioraton rate of the structure. Relative importance among these citeria was determined by using Analytical Hierarchy Method (AHP). On this basis, a multi-criteria model to be used for the selection of a set of structures\ud that have refurbishment priority in the case of limited financial contribution was developed. Refurbishment priority was identified for a group of structures that have, as a whole, a maximum overall benefit with respect to the selected criteria and their relative importance. Further, the analysis of the influence of the financial constraint magnitude upon the selection of structures to be repaired and the accompanying benefits ( that can facilitate the decision of the decision-makers' side) was carried out. The obtained results show that the proposed model can serve as an efficient tool used in rational selection of group of structures yielding the maximum overall benefit, and in analysis of possibilitie that lead to additional benefit with minimum financial input