Study of intermolecular interactions of piroxicam polymorphs / 药学学报

Piroxicam has polymorphism. Different crystalline forms can exhibit different physicochemical properties and biological activities. Analysis of the intermolecular interactions is essential to reveal the formation mechanism and differences of polymorphs. In this paper, Hirshfeld surface analysis and semi-empirical methods were used to calculate and analyze the intermolecular interactions in seven polymorphic forms of piroxicam. The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions, among which H…H, O…H/H…O and N…H/H…N interactions account for 95% of the total energy. There are differences in the proportion and distribution of the forces of different crystal forms. The energy calculation shows that the lattice energy of the hydrate is significantly lower than that of the anhydrous forms, and in the specific energy distribution, the contribution of the dispersion force is the most prominent. Further interaction energy analysis was found that within the distance of 3.8 Å from the center of the piroxicam molecule, different crystalline forms of piroxicam molecule have different interaction energies with surrounding molecules.

Preparation, characterization and improved solubility of ticagrelor salts / 药学学报

Four salts of ticagrelor, ticagrelor-3,5-dinitrobenzoic acid, ticagrelor-pyrazinamide, ticagrelor-D-proline and ticagrelor-L-proline were prepared by solvent suspension and liquid-assisted grinding to improve the solubility of ticagrelor. The compounds were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, elemental analysis, and the intermolecular salt-bonding forces were analyzed. The equilibrium solubility of salts and pure drug in hydrochloride buffer pH 1.2 and phosphate buffer pH 6.8 were measured by high-performance liquid chromatography. Ticagrelor was salted with 3,5-dinitrobenzoic acid, pyrazinamide, D-proline, L-proline all in a stoichiometric ratio of 1∶1; with the exception of ticagrelor-D-proline, the solubility of the other three salts provided significantly improved solubility in hydrochloride buffer pH 1.2, and the equilibrium solubility of ticagrelor-3,5-dinitrobenzoic acid was increased by approximately 1.7 folds as compared to pure drug. Salt-forming technology is convenient and can improve the solubility of ticagrelor.

The effects of GABAergic neurotransmitters and GABAA receptors on the auditory afferent pathway in the brainstem analyzed by optical recording / 中国应用生理学杂志

<p><b>AIM</b>To explore the influence of GABAergic neurotransmitters and GABAA receptors on the auditory afferent impulses recorded in the brainstem evoked by electro-stimulation.</p><p><b>METHODS</b>Brainstem slices were prepared using ddy/ddy mice of postnatal 0-5th days. The brainstem slices were stained with a voltage-sensitive dye(NK3041). The cut end of the vestibulocochlear nerve (nVIIIth) connected with slices was stimulated by a tungsten electrode, a 16 x 16 pixels silicon photodiode array apparatus was used to record the optical mapping from auditory brainstem slices. The data were analyzed by ARGUS-50/PDA software.</p><p><b>RESULTS</b>The spatial-temporal patterns of the excitatory propagation from the vestibulocochlear nerve (nVIIIth) to cochlear nucleus and vestibular nucleus were displayed with multiple-sites optical recording. The optical signal coming from one pixel consisted of a fast spike-like response and a following slow response. Inhibitory neurotransmitter GABA decreased the fast spike-like response and following slow response of evoked optical signals, while an antagonist BMI against GABAA receptors increased the both responses.</p><p><b>CONCLUSION</b>A 16 x 16 pixel silicon photodiode array apparatus can be used to record multiple-sites optical mapping evoked by electro-stimulation to the cut end of the vestibulocochlear nerve. The every optical signal consists of both presynaptic and postsynaptic elements. Inhibitory neurotransmitter GABA and an antagonist BMI of GABAA receptors can modulate the excitatory propagation of evoked optical signals.</p>

Effects of S100A4 expressed In white matter astrocytes on sensory neurite outgrowth in vitro / 中华物理医学与康复杂志

Objective To investigate the role of white matter astrocytes and their specific protein S100A4 in sensory neurite outgrowth in vitro.Methods White matter astrocyte cultures expressing S100A4 were prepared. Dissociated adult dorsal root ganglion(DRG)cells were placed on the top of the astrocytes and co-cultured for 6,12, 18,24 hours.Small interfering S100A4 RNA was used to eliminate S100A4 expression.The growth of DRG cell neu- rites on S100A4-sileneed and S100A4-expressing astrocytes was compared.Results 12,18 and 24 hours after the co-culture with S100A4-expressing or S100A4-silenced astroeytes,neurite growth from the DRG cells was observed. Neurite outgrowth was significantly greater in S100A4 siRNA treated cultures compared to control siRNA treated white matter astrocyte cultures.Conclusion These findings suggest that white matter astroeytes are able to support axonal regeneration and,furthermore,that administration of small interfering S100A4 RNA provides strong additional support for axon regeneration.

Relationship between amyloid beta-protein and oxidative stress and the protective role of pituitary adenylate cyclase activating polypeptide against oxidative stress induced damage on neuro-2a cells / 中国应用生理学杂志

<p><b>AIM</b>To observe the relationship between amyloid beta-protein (Abeta) and oxidative stress and the protective role of pituitary adenylate cyclase activating polypeptide (PACAP, PACAP-27) against damage induced by oxidative stress (H2O2) in neurem-2a cells.</p><p><b>METHODS</b>With cultured neuro-2a cells the cell survival and apoptosis were measured by MTT assay, Hoechest33258 staining, DNA ladder and the percentage of small DNA fragment.</p><p><b>RESULTS</b>Concentration-dependent toxicity was induced with H2O2 treatment for 24 h. The neurotoxicity of H2O2 was increased by about 10 times with cotreatment neurons with amyloid beta-protein fragment 25-35 (Abeta(25-35)). While decrease the percentage of small DNA fragmentation the cell survival was increased with co-treatment with PACAP-27(which were added to the culture everyday). The effect of PACAP was not reversed with antagonist of PACAP receptor, PACAP(6-27).</p><p><b>CONCLUSION</b>Abeta and H2O2 can promote each other's neurotoxicity. Cultured neurons were protected by PACAP27 from the neurotoxicity of H2O2 but not through the activation of PACAP-27 receptor.</p>