Polarographische Bestimmung des Pyridoxols in pharmazeutischen Präparaten

Zusammenfassung Es wird eine neue polarographische Methode zur direkten Bestimmung des Pyridoxols in Injektionspräparaten und Tabletten beschrieben. Die ausgearbeitete Methode beruht auf der polarographischen Reduktion des Pyridoxolmoleküls im Milieu von Ammoniak-Ammoniumchlorid-Puffern und weiter auf der Bildung einer katalytischen Stufe des Pyridoxols in Veronalpuffern. Die polarographische Methode ist rascher und in manchen Fällen genauer und empfindlicher als die bisher in Gebrauch stehenden Methoden. Die Anwesenheit der in den Präparaten laufend vorkommenden Begleitstoffe des Pyridoxols stört nicht die polarographische Bestimmung. Die Methode kann auch zur Bestimmung des 3-Hydroxy-4-methoxymethyl-5-oxymethyl-2-methylpyridins benutzt werden, das ein Zwischenprodukt bei der Pyridoxolerzeugung ist.

---

Summary A new polarographic method is described for the direct determination of pyridoxol in injection preparations and tablets. This method is based on the polarographic reduction of the pyridoxol in ammonia-ammonium chloride buffer medium and also on the formation of a catalytic stage of the pyridoxol in veronal buffers. The polarographic method is faster and in many cases more accurate and more sensitive than the methods now in use. The presence of the materials which always accompany the pyridoxol in the preparations does not interfere with the polarographic determination. The method can likewise be used for determining 3-hydroxy-4-methoxymethyl-5-oxymethyl-2-methylpyridine, which is an intermediate product in the manufacture of pyridoxol.

---

Résumé On décrit une nouvelle méthode polarographique pour le dosage direct du pyridoxol dans les préparations pour injections et dans les comprimés. La méthode élaborée repose sur la réduction polarographique de la molécule de pyridoxol dans le milieu tampon ammoniaque-chlorure d'ammonium, et, en outre, sur la formation d'une phase catalytique du pyridoxol dans les tampons au véronal. La méthode polarographique est plus rapide et dans de nombreux cas plus exacte et plus sensible que les méthodes utilisées jusqu'ici. La présence d'impuretés existant couramment dans les préparations à côté du pyridoxol ne gêne pas le dosage polarographique. On peut aussi utiliser la méthode pour le dosage de l'hydroxy-3 méthoxyméthyl-4 oxyméthyl-5 méthyl-2 pyridine, substance intermédiaire dans la préparation du pyridoxol.

---

---

Herrn Dr.P. Zuman danken wit für Ratsehläge bei der Abfassung dieser Arbeit.     

Time-resolved fluorescence analysis of the mobile flavin cofactor in p -hydroxybenzoate hydroxylase

Conformational heterogeneity of the FAD cofactor in p-hydroxybenzoate hydroxylase (PHBH) was investigated with time-resolved polarized flavin fluorescence. For binary enzyme/substrate (analogue) complexes of wild-type PHBH and Tyr222 mutants, crystallographic studies have revealed two distinct flavin conformations; the ‘in’ conformation with the isoalloxazine ring located in the active site, and the ‘out’ conformation with the isoalloxazine ring disposed towards the protein surface. Fluorescence-lifetime analysis of these complexes revealed similar lifetime distributions for the ‘in’ and ‘out’ conformations. The reason for this is twofold. First, the active site of PHBH contains various potential fluorescence-quenching sites close to the flavin. Fluorescence analysis of uncomplexed PHBH Y222V and Y222A showed that Tyr222 is responsible for picosecond fluorescence quenching free enzyme. In addition, other potential quenching sites, including a tryptophan and two tyrosines involved in substrate binding, are located nearby. Since the shortest distance between these quenching sites and the isoalloxazine ring differs only little on average, these aromatic residues are likely to contribute to fluorescence quenching. Second, the effect of flavin conformation on the fluorescence lifetime distribution is blurred by binding of the aromatic substrates: saturation with aromatic substrates induces highly efficient fluorescence quenching. The flavin conformation is therefore only reflected in the small relative contributions of the longer lifetimes.     

Poly(lactic acid) composites with poly(lactic acid)‐modified carbon nanotubes

This work reports the study of the effect of chemical functionalization of carbon nanotubes on their dispersion in poly(lactic acid). The nanotubes were functionalized by the 1,3‐dipolar cycloaddition reaction, generating pyrrolidine groups at the nanotube surface. Further reaction of the pyrrolidine groups with poly(lactic acid) was studied in solution and in the polymer melt. The former involved refluxing the nanotubes in a dimethylformamide/polymer solution; the latter was carried out by direct melt mixing in a microcompounder. The carbon nanotubes collected after each process were characterized by thermogravimetry and by X‐ray photoelectron spectroscopy, showing evidence of polymer bonded to the nanotube surface only when the reaction was carried out in the polymer melt. The composites with polymer modified nanotubes present smaller average agglomerate area and a narrower agglomerate area distribution. In addition, they show improved tensile properties at low CNT concentration and present lower electrical resistivity. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3740–3750     

Detecting cortical lesions in multiple sclerosis at 7 T using white matter signal attenuation

Cortical lesions have recently been a focus of multiple sclerosis (MS) MR research. In this study, we present a white matter signal attenuating sequence optimized for cortical lesion detection at 7 T. The feasibility of white matter attenuation (WHAT) for cortical lesion detection was determined by scanning eight patients (four relapsing/remitting MS, four secondary progressive MS) at 7 T. WHAT showed excellent gray matter-white matter contrast, and cortical lesions were hyperintense to the surrounding cortical gray matter, The sequence was then optimized for cortical lesion detection by determining the set of sequence parameters that produced the best gray matter-cortical lesion contrast in a 10-min scan. Despite the B1 inhomogeneities common at ultra-high field strengths, WHAT with an adiabatic inversion pulse showed good cortical lesion detection and would be a valuable component of clinical MS imaging protocols.     

Determination of Ground State Vibrational Frequencies of Jet-Cooled Resorcinol by Means of Dispersed Fluorescence Spectroscopy and ab Initio Calculations

The vibrational frequencies of the electronic ground state of resorcinol have been determined via laser-induced dispersed fluorescence spectroscopy. An assignment based on comparison with ab initio calculations on the MP2 and B3LYP (6-311 G (d,p)) level is presented.     

Interchange-turbulence-based radial transport model for SOLPS-ITER: A COMPASS case study

Mean-field plasma edge transport codes such as SOLPS-ITER heavily rely on ad-hoc radial diffusion coefficients to approximately model anomalous transport. Such coefficients are experimentally determined and vary between different machines, and also depend on the operational regime and plasma location within the same device. Therefore, to match experimental data the modeller is required to manually tune several free parameters in expensive simulations, and the code's predictive capabilities are significantly downgraded. As a solution, a new model has been developed for SOLPS-ITER, solving an additional transport equation for the turbulent kinetic energy k, derived by consistently time-averaging the Braginskii equations, and including a diffusive closure for the anomalous particle flux. This closure model relates the anomalous diffusion coefficient to the local k value. The resulting equation structure and its closure are inspired by TOKAM2D isothermal interchange turbulence simulation results. Within this model, fewer and hopefully more universal free parameters are retained, thus improving the code's predictive capabilities. The new model has been tested on a COMPASS case for which upstream plasma profiles were available. Experimental data and a reference solution, obtained by matching the profiles through manual tuning of radial diffusivities, have been used to estimate the parameters of our new transport model. A ballooned particle diffusivity profile is retrieved by the new radial transport model, thanks to the proposed interchange drive. The obtained upstream profiles qualitatively agree with the experiment and prove the new model is a promising first attempt to be further refined.     

Controlling the early stages of pentacene growth by supersonic molecular beam deposition

The key role of the pentacene kinetic energy (Ek) in the early stages of growth on SiOx/Si is demonstrated: islands with smooth borders and increased coalescence differ remarkably from fractal-like thermal growth. Increasing Ek to 6.4 eV, the morphology evolves towards higher density of smaller islands. At higher coverage, coalescence grows with Ek up to a much more uniform, less defected monolayer. The growth, interpreted by the diffusion mediated model, shows the critical nucleus changing from 3 to 2 pentacene for Ek>5-6 eV. Optimal conditions to produce single crystalline films are envisaged.     

A zero topological entropy map with recurrent points not

We show that there is a continuous map of the unit interval into itself of type which has a trajectory disjoint from the set of recurrent points of , but contained in the closure of . In particular, is not closed. A function of type , with nonclosed set of recurrent points, was found by H. Chu and J. Xiong [Proc. Amer. Math. Soc. 97 (1986), 361-366]. However, there is no trajectory contained in , since any point in is eventually mapped into . Moreover, our construction is simpler.

We use to show that there is a continuous map of the interval of type for which the set of recurrent points is not an set. This example disproves a conjecture of A. N. Sharkovsky et al., from 1989. We also provide another application of .

     

The anxiolytic effects of midazolam during anticipation to pain revealed using fMRI

BACKGROUND AND PURPOSE: Functional neuroimaging can distinguish components of the pain experience associated with anticipation to pain from those associated with the experience of pain itself. Anticipation to pain is thought to increase the suffering of chronic pain patients. Inappropriate anxiety, of which anticipation is a component, is also a cause of disability. We present a pharmacological functional magnetic resonance imaging (fMRI) study in which we investigate the selective modulation by midazolam of brain activity associated with anticipation to pain compared to pain itself. METHODS: Eight right-handed male volunteers underwent fMRI combined with a thermal pain conditioning paradigm and midazolam (30 mug/kg) or saline administration on different occasions, with order randomized across volunteers. Volunteers learned to associate a colored light with either painful, hot stimulation or nonpainful, warm stimulation to the back of the left hand. RESULTS: Comparison of the period during thermal stimulation (pain-warm) revealed a network of brain activity commonly associated with noxious stimulation, including activities in the anterior cingulate cortex (ACC), the bilateral insular cortices (anterior and posterior), the thalamus, S1, the motor cortex, the brainstem, the prefrontal cortex and the cerebellum. Comparison of the periods preceding thermal stimulation (anticipation to pain-anticipation to warm) revealed activity principally in the ACC, the contralateral anterior insular cortex and the ipsilateral S2/posterior insula. Detected by a region-of-interest analysis, midazolam reduced the activity associated specifically with anticipation to pain while controlling for anticipation to warm. This was most significant in the contralateral anterior insula (P<.05). There were no significant drug effects on the activity associated with pain itself. CONCLUSION: In identifying a pharmacological effect on activity preceding but not during pain, we have successfully demonstrated an fMRI assay that can be used to study the action of anxiolytic agents in a relatively small cohort of humans.