New Pharmaceutical Salts of Trazodone.

New pharmaceutically acceptable salts of trazodone (trazodone hydrogen bromide and trazodone 1-hydroxy-2-naphthonic acid) for the treatment of central nervous system disorders are synthesized and described. Although trazodone salts are poorly crystalline, single-crystal X-ray diffraction data for trazodone 1-hydroxy-2-naphthonic acid were collected and analyzed as well as compared to the previously described crystal structure of commercially available trazodone hydrochloride. The powder samples of all new salts were characterized by Fourier transform infrared spectroscopy, X-ray diffraction and 13C solid-state nuclear magnetic resonance spectroscopy. Spectroscopic studies were supported by gauge including projector augmented wave (GIPAW) calculations of carbon chemical shielding constants. The main goal of our research was to find salts with better physicochemical properties and to make an attempt to associate them with both the anion structure and the most prominent interactions exhibited by the protonated trazodone cation. The dissolution profiles of trazodone from tablets prepared from various salts with lactose monohydrate were investigated. The studies revealed that salts with simple anions show a fast release of the drug while the presence of more complex anion, more strongly interacting with the cation, effects a slow-release profile of the active substance and can be used for the preparation of the tables with a delay or prolonged mode of action.

Spectroscopic analysis of the influence of various external factors on ethenzamide-glutaric acid (1:1) cocrystal formation.

Cocrystal formation may affect manufacturability (flow, compaction and processability) as well as solubility/dissolution, hygroscopicity and stability properties of drugs. Therefore, cocrystallization could be used to improve the pharmaceutical properties of low-soluble drugs such as ethenzamide. In this project, solid-state nuclear magnetic resonance and Fourier transform infrared spectroscopy studies were performed for ethenzamide-glutaric acid to obtain more information about the ethenzamide cocrystallization process. The impact of the grinding time of the physical mixture (ethenzamide-glutaric acid) on cocrystal formation and the further spontaneous cocrystallization was evaluated using spectroscopic methods and curve-fitting analysis of the spectra. The influence of pressure on the yield of cocrystal formation was also described. Additionally, studies on the effect of magic-angle spinning during solid-state nuclear magnetic resonance spectra collection on the initiation of cocrystal formation, have been performed. Based on this research, conclusions regarding the influence of the different external factors, such as pressure during the tableting process and grinding time, on the cocrystal formation have been drawn for ethenzamide cocrystals.

Variability of laying hen behaviour depending on the breed.

OBJECTIVE: For many generations, most species of farm animals have been subjected to intense and strictly targeted selection for improvement of their performance traits. This has led to substantial changes in animal anatomy and physiology, which resulted in considerable differences between the current animal breeds and their wild ancestors. The aim of the study was to determine whether there is breed-specific variability in behaviour as well as differences in emotional reactivity and preferences of laying hens. METHODS: The investigations involved 50 Green-legged Partridge, 50 Polbar, and 50 Leghorn hens. All birds were kept in the same conditions, and the behavioural tests were carried out at 30 weeks of age. We used the tonic immobility test and a modified open-field test including such objects as water, commercial feed, feed enriched with cereal grains, finely cut straw, and insect larvae, a sandpit, a mirror, and a shelter imitating a hen nest. RESULTS: The research results demonstrate that the birds of the analysed breeds differ not only in the excitability and emotional reactivity but, importantly, also in the preferences for environment-enriching elements. Ensuring hens' well-being should therefore be based on environmental modifications that will facilitate acquisition of essential elements of chickens' behaviour. The greatest emotional reactivity was found in the Leghorn breed, which may be a result of correlated selection aimed at an increase in chicken productivity. CONCLUSION: The differences in the behaviour of the birds from the analysed breeds indicate that laying hens cannot be regarded as one group of animals with the same environmental requirements.

Structural Characterization and Pharmaceutical Properties of Three Novel Cocrystals of Ethenzamide With Aliphatic Dicarboxylic Acids.

Ethenzamide (ET) was screened in cocrystallization experiments with pharmaceutically acceptable coformer molecules to discover materials of improved physicochemical properties, that is, higher solubility and better stability. Three novel cocrystals of ET with glutaric, malonic, and maleic acids were obtained by neat grinding and slow evaporation from solution. The purpose of the study was to notice the changes in the geometry and interactions of ET molecule in crystalline phase introduced by different acid and relate them to physicochemical properties of pure ET. Therefore, the crystal structure of the cocrystals was determined by single crystal X-ray diffraction analysis. The powder samples were characterized by differential scanning calorimetry, Fourier-transform infrared spectroscopy, and 13C and 15N solid-state nuclear magnetic resonance spectroscopy. Spectroscopic studies were supported by gauge including projector augmented wave calculations of chemical shielding constants. The high stability of cocrystals during direct compression was proved. The solubility in simulated gastric fluids for studied cocrystals appeared to be approximately 1.6 times-fold higher than ET. The dissolution rates of all ET cocrystals were not faster than the pure drug, but after 240 min, more drugs were released.

Transcriptional profiling of catalase genes in juglone-treated seeds of maize (Zea mays L.) and wheat (Triticum aestivum L.).

The major aim of the present study was to investigate the influence of juglone (JU; 5-hydroxy-1,4-naphthoquinone) treatments on the expression level of Cat1, Cat2 and Cat3 genes, encoding the respective catalase isozymes in maize (Zea mays L.) and wheat (Triticum aestivum L.) seeds. In parallel, germination efficiency, catalase (CAT) activity and hydrogen peroxide (H2O2) content in juglone-exposed cereal seeds were assessed. Juglone applications significantly stimulated abundance of three target catalase transcripts as well as induced CAT activity and generation of H2O2 in both maize and wheat kernels. Furthermore, germination process of juglone-affected maize seeds was more severe suppressed than in case of wheat kernels. The role of juglone in triggering the oxidative stress as well as antioxidative responses in seeds of the studied model cereal species are discussed.

Imaging the healing murine myocardial infarct in vivo: ultrasound, magnetic resonance imaging and fluorescence molecular tomography.

Improved understanding of the processes involved in infarct healing is required for identification of novel therapeutic targets to limit infarct expansion and consequent long-term ventricular remodelling after myocardial infarction. Infarct healing can be modelled effectively in murine models of coronary artery ligation. While imaging the murine heart is challenging due to its size and high rate of contraction, advances in preclinical imaging now permit accurate assessment of myocardial structure and function in vivo after myocardial infarction. Furthermore, rapid development of a range of molecular probes for use in a number of imaging modalities allows more detailed in vivo analysis of processes, including inflammation, fibrosis and angiogenesis. Here we consider the practical application of in vivo imaging by magnetic resonance imaging, ultrasound and fluorescence molecular tomography for assessment of infarct healing in the mouse.

Improved heart function follows enhanced inflammatory cell recruitment and angiogenesis in 11betaHSD1-deficient mice post-MI.

AIMS: Mice unable to locally regenerate corticosterone due to deficiency of 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD1) have enhanced angiogenesis during acute myocardial infarct healing. The present study investigates the hypotheses that in these mice (i) inflammation and angiogenic signalling are promoted and (ii) longer-term remodelling and function are improved. METHODS AND RESULTS: Myocardial infarction (MI) was induced by coronary artery ligation in 11ßHSD1(-/-) and wild-type (C57BL/6) mice. Studies were terminated 2, 4, 7, and 28 days post-surgery. Increased vessel density (CD31 immunoreactivity) on the infarct border was confirmed 7 days after MI in 11ßHSD1(-/-) hearts (P < 0.05) and was accompanied by improved ejection fraction (ultrasound) compared with C57BL/6. During wound healing, recruitment of neutrophils (at 2 days after MI) and macrophages (from 4 days after MI) and expression of monocyte-chemoattractant protein-1 was increased in 11ßHSD1(-/-) compared with C57BL/6 hearts (P < 0.05). Recruitment of alternatively activated YM1-positive macrophages was particularly enhanced in the period preceding increased vessel density and was accompanied by increased expression of pro-angiogenic IL-8. By 28 days post-MI, when the infarct scar had matured, higher vessel density was maintained in 11ßHSD1(-/-) hearts and vessels were smooth-muscle coated. Infarct scars were thicker (P < 0.001) in 11ßHSD1(-/-) compared with C57BL/6 hearts and ejection fraction was higher (P < 0.05). CONCLUSION: Increased vessel density in healing infarcts of mice deficient in 11(-/-)HSD1 follows recruitment of pro-reparative macrophages and increased pro-angiogenic signalling. Mature infarcts show less thinning and cardiac function is improved relative to wild-type mice, suggesting that 11ßHSD1 may be a novel therapeutic target after MI.