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Introduction A network meta-analysis (NMA) was performed to assess the efficacy and safety of avatrombopag, relative to eltrombopag, romiplostim, and fostamatinib, for patients with chronic immune thrombocytopenia (ITP) not responding adequately to corticosteroids. Methods A systematic search of publication and clinical trial databases was conducted to identify relevant randomized controlled trials (RCTs) and observational studies. Data from eligible studies were extracted and analyzed in a Bayesian framework using relative effect sizes vs placebo. Outcomes included durable platelet response; need for rescue therapy; reduction in use of concomitant ITP medication; incidence of any or World Health Organization (WHO) grade 2–4 bleeding events, and any adverse events. Results were reported as odds ratios or incidence rate ratios (IRR) with 95% credible intervals (CrIs). Results The NMA included seven phase 3 RCTs. Compared with placebo, avatrombopag was associated with statistically significant improvements in durable platelet response, reduction in use of concomitant ITP medication, and incidence of any bleeding events. Statistically significant differences vs placebo were also observed for durable platelet response and need for rescue therapy (eltrombopag, romiplostim, and fostamatinib); reduction in use of concomitant ITP medication (eltrombopag and romiplostim); incidence of any bleeding events (fostamatinib); and incidence of WHO grade 2–4 bleeding events (romiplostim and fostamatinib). No statistically significant differences were observed for any adverse events. Avatrombopag was associated with a statistically significant lower incidence of any bleeding events vs eltrombopag (IRR 0.38 [95% CrI 0.19, 0.75]) and romiplostim (IRR 0.38 [95% Crl 0.17, 0.86]); no other between-treatment differences were observed. Conclusion In this NMA, avatrombopag significantly increased the chance of achieving durable platelet response and reducing the use of concomitant ITP medication vs placebo, and significantly reduced the incidence of any bleeding events compared with placebo, eltrombopag, and romiplostim. The study aims to help guide clinicians managing patients with chronic ITP and insufficient response to previous treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01752-4.

The opioid-induced analgesia is associated with a number of side effects such as addiction, tolerance and respiratory depression. The involvement of neuropeptide FF (NPFF) in modulation of pain perception, opioid-induced tolerance and dependence was well documented in contrast to respiratory depression. Therefore, the aim of the present study was to examine the potency of NPFF to block post-opioid respiratory depression, one of the main adverse effects of opioid therapy. Urethane-chloralose anaesthetized Wistar rats were injected either intravenously (iv) or intracerebroventricularly (icv) with various doses of NPFF prior to iv endomorphin-1 (EM-1) administration. Iv NPFF diminished the number of EM-1-induced apneas without affecting their length and without influence on the EM-1 induced blood pressure decline. Icv pretreatment with NPFF abolished the occurrence of post-EM-1 apneas and reduced also the maximal drop in blood pressure and heart rate. These effects were completely blocked by the NPFF receptor antagonist RF9, which was given as a mixture with NPFF before systemic EM-1 administration. In conclusion, our results showed that centrally administered neuropeptide FF is effective in preventing apnea evoked by stimulation of &mu, opioid receptors and the effect was due to activation of central NPFF receptors. Our finding indicates a potential target for reversal of opioid-induced respiratory depression.

The behavioral responses exerted by spinal administration of the opioid-neurotensin hybrid peptide, PK23, were studied in adult male rats. The antinociceptive effect upon exposure to a thermal stimulus, as well as tolerance development, was assessed in an acute pain model. The PK23 chimera at a dose of 10 nmol/rat produced a potent pain-relieving effect, especially after its intrathecal administration. Compared with intrathecal morphine, this novel compound was found to possess a favourable side effect profile characterized by a reduced scratch reflex, delayed development of analgesic tolerance or an absence of motor impairments when given in the same manner, though some animals died following barrel rotation as a result of its i.c.v. administration (in particular at doses higher than 10 nmol/rat). Nonetheless, these results suggest the potential use of hybrid compounds encompassing both opioid and neurotensin structural fragments in pain management. This highlights the enormous potential of synthetic neurotensin analogues as promising future analgesics., Graphical abstract PK23 is a bifunctional compound consisting of both opioid and neurotensin fragments fused into one molecule. It mediates dose- and time-dependent antinociceptive responses when administered either centrally or peripherally, likely due to its interaction with μ opioid and neurotensin type 1 (NTS1) receptors.Image 1

AWL3106 composed of opioid (dermorphin) and tachykinin (substance P7-11) pharmacophores is a new compound with high analgesic potency and markedly reduced ability to induce tolerance and dependence. The present study aimed to determine the respiratory and cardiovascular responses evoked by this peptide in urethane-chloralose anaesthetized, spontaneously breathing rats in the presence or absence of vagal connection. Intravenous injection of AWL3106 at a dose of 0.3μmol/kg in intact rats resulted in apnoea lasting 5.1 ± 0.7s. Breathing that followed was of diminished frequency (F) and augmented tidal volume (VT) with no significant impact on minute ventilation. AWL3106-challenge induced biphasic fall in arterial blood pressure with no effect on heart rate. Midcervical and supranodosal sectioning the vagal nerves prevented the occurrence of the apnoea and abrogated the post-AWL3106 reduction in F but failed to eliminate the increase in VT. Hypotensive response appeared to be less profound following supranodose vagotomy. NaloxoneHCl abolished solely the occurrence of apnoea. However additional blockade of tachykinin NK1 receptors with SR140333 was required to abolish VT increase, deceleration of breathing and to markedly suppress AWL3106-induced hypotension. The present study shows that extravagally controlled stimulation of VT maintains fairly regular ventilation by levelling the bradypnoeic effects. Although the peptide showed no cardiac effects, hypotension occurring beyond the vagal loop may limit future therapeutic benefits of this chimeric compound.

Aim Chimeric compound – PK20 despite its therapeutic activity on nociceptive and inflammatory processes may affect respiration and blood pressure. Our objective was to evaluate influence of the hybrid composed of endomorphin-2 and neurotensin fragments on ventilation, heart rate and blood pressure in anesthetized and awake rats. Methods The effects of PK20 (1 mg/kg) were studied either after its intravenous administration in anesthetized rats or intraperitoneal injection in awake state. Tidal volume and the timing components of the breathing pattern, arterial blood pressure, and heart rate were recorded. Results Intravenous administration of PK20 in the neurally intact rats evoked a dose-dependent apnoea followed by a transient insignificant increase in tidal volume and breathing rate. The blood pressure changes were biphasic: transient increase was replaced by prolonged hypotension. Midcervical vagotomy abrogated all post-PK20 respiratory effects. Hypotension was eliminated after blockade of neurotensin NTS 1 receptor, while respiratory changes were reduced by blockade of both: NTS 1 and μ opioid receptors. After PK20 intraperitoneal injection awake rats did not show any significant changes in ventilation and blood pressure. Conclusion This chimeric peptide should be used with care via intravenous administration in anesthetized animals since PK20 may evoke respiratory apnoea and hypotension. Nevertheless, applied intraperitoneally in the same dose in conscious rats induced no adverse effects.

We report a strategy for preparing barium titanate precursor, being the composite of titanate nanosheets (TN) with barium ions (Ba-TN), which subjected to step sintering allows obtaining TiO2 rich barium titanate ceramics of stoichiometry BaTi4O9 or Ba2Ti9O20. These compounds are important in modern electronics due to their required dielectric properties and grains’ size that can be preserved in nanometric range. The morphology studies, structural characterization, and dielectric investigations were performed simultaneously in each step of Ba-TN calcinations in order to properly characterize type of obtained ceramic, its grains’ morphology, and dielectric properties. The Ba-TN precursor can be sintered at given temperatures, so that its dielectric permittivity can be tuned between 25 and 42 with controlled temperature coefficients that change from negative 32 ppm/°C for Ba-TN sintered at 900°C up to positive 37 ppm/°C after calcination at 1300°C. XRD analysis and Raman investigations performed for the Ba-TN in the temperature range of 900÷1250°C showed that below 1100°C we obtained as a main phase BaTi4O9, whereas the higher calcinations temperature transformed Ba-TN into Ba2Ti9O20. Taking into account trend of device miniaturization and nanoscopic size requirements, temperatures of 900°C and 1100°C seem to be an optimal condition for Ba-TN precursor calcinations that guarantee the satisfactory value of dielectric permittivity (ε=26 and 32) and ceramic grains with a mean size of ~180 nm and ~550 nm, respectively.

Sulforaphane-modified selenium nanoparticles can be prepared in a simple aqueous-phase redox reaction through reduction of selenite with ascorbic acid. The sulforaphane molecules present in the reaction mixture adsorb on the nanoparticle surface, forming an adlayer. The resulting conjugate was examined with several physicochemical techniques, including microscopy, spectroscopy, x-ray diffraction, dynamic light scattering and zeta potential measurements. As shown in in vivo investigations on rats, the nanomaterial administered intraperitoneally is eliminated mainly in urine (and, to a lesser extent, in feces); however, it is also retained in the body. The modified nanoparticles mainly accumulate in the liver, but the basic parameters of blood and urine remain within normal limits. The sulforaphane-conjugated nanoparticles reveal considerable anticancer action, as demonstrated on several cancer cell cultures in vitro. This finding is due to the synergistic effect of elemental selenium and sulforaphane molecules assembled in one nanostructure (conjugate). On the other hand, the cytotoxic action on normal cells is relatively low. The high antitumor activity and selectivity of the conjugate with respect to diseased and healthy cells is extremely promising from the point of view of cancer treatment.

Experiments were performed in anaesthetized, spontaneously breathing rats to: (1) analyse the respiratory and cardiovascular effects of C-terminal fragment of substance P (AWL2077) as referred to those exerted by the parent undecapeptide, (2) determine the involvement of lung vagal afferents to these responses. Each peptide was injected intravenously at a dose of 0.3μmol/kg into neurally intact or midcervically vagotomized rats. Administration of both compounds decreased tidal volume, minute ventilation, mean arterial blood pressure and heart rate, showing stimulatory (SP) and depressive (AWL2077) effects on the rate of breathing. Midcervical vagotomy reversed (post-SP) and precluded (post-AWL2077) respiratory rate responses and eliminated bradycardia evoked by both peptides. These findings indicate that the examined C-terminal pentapeptide was convergent with, but less potent than substance P in central depression of tidal volume and displayed divergence in the peripheral effect on respiratory timing.

Effects of the elevated temperature on the structure evolution of the ZnO nanorod array (ZNA) and their hybrid nanocomposite with layered (tetramethyl)ammonium titanate (LTMAT) prepared by the liquid phase deposition were investigated. The vertically oriented ZnO nanorods were deposited on a quartz plate by a chemical bath deposition method and then they were penetrated by the LTMAT using the dip-coating method from the water solution. As a result of such an experimental procedure, an assembly composed of the ZNA with LTMAT was obtained and called hybrid nanocomposite. Since the LTMAT converts to TiO2 upon subsequent sintering at 350 °C, it can be regarded as TiO2 precursor for the thermal treatment experiments. The experiments with ZNA and their hybrid nanocomposite at the elevated temperature revealed coalescence of the deposited ZnO nanorods and crystallization of zinc titanate with Zn2TiO4 stoichiometry.

PK20M (Dmt-D-Lys-Phe-Phe-OH) is a novel modified endomorphin-2 (EM-2) peptide producing strong dose- and time-dependent antinociceptive activity. Yet its prototype, endogenous EM-2, has been reported to trigger respiratory and vascular effects such as apnea and hypotension. The purpose of this study was to investigate the potency of the PK20M to evoke respiratory and cardiovascular responses in comparison to endogenous endomorphins. The engagement of the vagal pathway and μ opioid receptors in mediation of these responses was investigated. The effects of intravenous injections of PK20M, EM-1, and EM-2 were studied in anaesthetized, spontaneously breathing rats. The main dose-dependent effect of all endomorphins in the intact rats was immediate apnea, blood pressure and heart rate decrease. PK20M produced apnea in at least half of the intact animals in a much smaller dose than EM-1 and EM-2. The effects of all compounds were abrogated by pre-treatment with MNLX, a peripherally acting μ receptor antagonist. Cervical vagotomy eliminated arrest of breathing in the case of each tested compound. Hypotension was reduced by vagi section only after EM-1 and EM-2 administration. Our results demonstrated that apnea and bradycardia caused by systemic injection of all endomorphins were mediated via activation of μ vagal opioid receptors. The hypotension depended on intact vagi nerves only in the case of EM-1 and EM-2, whereas PK20M decreased blood pressure via other mechanisms outside vagal innervation. Modified opioid agonist is more potent in evoking extended hypotension; at the same time, it produces an arrest of breathing less frequently than its prototype EM-2.

BACKGROUND Inhaled corticosteroids used for treating persistent asthma can suppress adrenal cortisol secretion. This inhibition of endogenous cortisol secretion is an important marker of systemic steroid activity. Although meta-analyses have demonstrated a dose-dependent suppression of cortisol by inhaled corticosteroids, regardless of inhaler type, the impact of novel freon-free inhaled corticosteroid preparations has not been reviewed. OBJECTIVE The aim of this study was to synthesize all currently available studies on novel inhaled corticosteroid preparations, including ciclesonide, beclomethasone dipropionate, budesonide, and fluticasone propionate. In particular, we aimed to compare the effect of ciclesonide on cortisol suppression with other existing preparations. METHODS We carried out a systematic review of the medical data bases on cortisol suppression in patients due to inhaled corticosteroids. A multivariate regression model was used to determine dose-dependent relationships between each inhaled corticosteroid and cortisol suppression with respect to age, type of inhaler, and study design. RESULTS From analysis of 64 studies identified in the review, the strongest dose-response urinary cortisol suppression was observed in patients treated with beclomethasone (8.4% per 100 μg; p = 0.029), followed by fluticasone (3.2% per 100 μg; p < 0.001), and budesonide (3.1% per 100 μg; p = 0.001). No significant urinary cortisol suppression was associated with ciclesonide treatment (1.8% per 100 μg; p = 0.267). Although ciclesonide did not affect cortisol levels, this appeared to be due to its unique pharmacokinetic properties rather than the use of a novel formulation. CONCLUSION Our findings indicated that the introduction of novel freon-free delivery technologies for inhaled corticosteroids had not eliminated adverse adrenal suppression of cortisol secretion.

In this paper, we report a strategy for preparing an inorganic zinc titanate precursor by applying a chemical bath deposition method (CBD) to ZnO nanocrystals in an aqueous layered titanate colloid. The zinc titanate precursor, obtained as a precipitate, undergoes profound changes under the influence of elevated temperatures in normal atmospheric conditions and allows us to obtain zinc titanate ZnTiO3 with a rhombohedral symmetry. Investigations of its dielectric properties enabled us to determine a dielectric permittivity (ɛ) of 25, a low loss factor tan(δ)

In this paper, dielectric spectroscopy investigations of organic–inorganic hybrid composite obtained from (2-hydroxypropyl)cellulose (HPC) with nanosheet crystallites of quasi-TiO2 are presented. This hybrid belongs to the class of composites, which have no covalent bonds between organic and inorganic constituents and the behaviour of composite is determined mainly by interface of two constituents. The analysis of the molecular dynamics of the hybrid system reveals the influence of the nanosheet crystallites of quasi-TiO2 on the relaxation processes of HPC matrix. The relaxation strength of γ process strongly increases in composite as compared to neat HPC. A shift to higher temperature has been evidenced in the case of α and β processes. A higher value of the slope of the maximum frequency vs. the inverse temperature for the α-relaxation of the composite has been observed. At high temperatures the mesomorphic behaviour of HPC has been drastically reduced in the composite. The results of our investigations are interpreted in terms of a presence of intermolecular forces between HPC and nanosheet crystallites of quasi-TiO2.

Our results in the field of adopting the chemical bath deposition method (CBD) for the deposition of the nanostructures of copper compounds are presented in this work. The deposition of copper compounds by means of the CBD method was carried out at the water solution of copper nitrate (acetate) salts and hexamethylenetetramine. There are two distinct periods in the deposition of copper compounds in the same bath. At the shorter deposition time the good quality nanocrystals of the copper hydroxy nitrate (acetate) salts with a different morphology are obtained. Decomposition of the copper salts to the CuO in the water bath can be observed after several hours of the copper hydroxy salts deposition. The SEM images and the XRD patterns of the CuO layer, which was produced by decomposition of copper hydroxy salts by the CBD method, show a morphology and texture different from the CuO layer prepared by thermal decomposition of the deposited copper hydroxy salts at an elevated temperature. It has been suggested that the main force in decomposition of copper hydroxy salts to CuO in the course of CBD process may be related with a strain, which exists between the CuO nanoparticles on the modified glass substrate and the deposited copper hydroxy salt. The decomposition reaction of copper hydroxy salts in the solid phase may be accelerated by a strain. The influence of the strain on the morphology of CuO nanostructures is demonstrated on the basis of the basic copper nitrate salt hybridised with titanate nanosheets.

In this paper we concentrate on the general behavior of oxotitanium hydrosol, which was earlier developed by us as a precursor of the TiO2 nanoparticles and nanocomposite. The oxotitanium hydrosol was synthesized by the chemical decomposition of a molecular complex of the methacrylic acid/(tetra-isopropyl)orthotitanate (MAA/TIPT) by means of the hydrogen peroxide. The raw product chemical decomposition of MAA/TIPT is the colloidal suspension of the oxotitanium compound in the water. The oxotitanium compound was separated from hydrosol and identified on the basis of X-ray and Raman spectroscopy investigations. The status of water in the hydrosol was also investigated by the Raman spectroscopy. The photophysical behaviors of the oxotitanium hydrosol on the basis of the light absorption and photoluminescence (PL) investigations are presented. The light absorption (260 nm) and PL emission (313 nm) allow us to identify the inorganic phase of hydrosol as nanosheets' crystallites of quasi-TiO2. Macromolecular nature of nanosheets of quasi-TiO2 was revealed only for a higher concentration solution of nanosheets' crystallites of quasi-TiO2 at the hydrosol. A macromolecular nature of nanosheets of quasi-TiO2 by the red shift of absorption edge and PL wavelength with increase in the concentration of the oxotitanium hydrosol as well as the formation of hydrogels and birefringence developed under an influence of mechanical shearing is evidenced. Copyright © 2009 John Wiley & Sons, Ltd.

A new method of synthesis of TiO2 nanoparticles as well as preparation of the organic–inorganic hybrid nanocomposite films of (hydroxypropyl)cellulose (HPC)/TiO2 is presented. At the first stage, the oxotitanium hydrogel phase was obtained by the mineralization of (tetra-isopropyl)orthotitanate (TIPT) modified by the methacrylic acid (MAA) in 15 wt% solution of H2O2 at room temperature and subsequent annealing at the temperature of 85°C. The crystallization of the nanoparticles of TiO2 was conducted at the oxotitanium hydrogel phase at temperatures around 120°C in the closed vessel. Nanocomposite hybrid films were prepared by the casting method from a solution of HPC and TiO2 nanoparticles in the water. The films of nanocomposite with 10 µm thickness are transparent to visible light and have a lower glass transition temperature compared with HPC in the bulk. This shift of the glass transition is interpreted in terms of packing density of HPC in the interface of HPC nanocomposite with TiO2. The X-ray diffraction pattern of the nanocomposite film suggests a lower amount of mesomorphic phase of HPC in the composite compared with HPC in the bulk. Copyright © 2007 John Wiley & Sons, Ltd.

The respiratory effects of stimulation of mu-opioid receptors were studied in spontaneously breathing anaesthetized rats that were either neurally intact or subjected to bilateral supranodosal vagotomy. An intravenous dermorphin bolus of 0.5 mg/kg evoked the apnea followed by breathing of reduced rate and compensatory augmentation of tidal volume, which resulted in an invariable minute ventilation. Cardiovascular effects consisted of hypotension and temporary fall in heart rate. In rats initially treated by supranodosal vagotomy, dermorphin did not evoke any respiratory and cardiovascular effects. These results indicate that vagal pathway and the nodose ganglia are involved in dermorphin-induced respiratory depression.

The nanocomposite of the (hydroxypropyl)cellulose–titania hybrid was prepared using the (hydroxypropyl)cellulose (HPC) and (tetra-isopropyl)orthotitanate (TIPT) modified by the methacrylic acid (MAA) as a sol–gel precursor. The Raman investigations of the TIPT with MAA mixtures revealed that these mixtures formed an intermolecular complex determined by the non-hydrolytic condensation of the constituents. In spite of this, the MAA/TIPT precursor can be used as a solvent for the HPC. The high viscosity of the homogenous liquid of HPC in the TIPT/MAA system was obtained and the sol–gel process under an influence of the moisture from the air could be conducted. The Raman investigations of HPC–titania hybrid showed octahedrally coordinated titania atoms [TiO6] embodied in the HPC environment. Although the chelating bond between the octahedrally coordinated titania [TiO6] and the MAA still occurred. The nanosize properties of TiO2 prepared by calcinations of HPC–titania hybrids were studied by the Raman spectroscopy, X-ray investigations and the scanning electron microscopy (SEM). Copyright © 2007 John Wiley & Sons, Ltd.

The process of crosslinking of the hydrogel, derived from lyotropic liquid crystalline (LLC) phases of hydroxypropylcellulose/acrylic acid-water, by calcium ions was studied by means of Raman and dielectric spectroscopy. Formation of salt by poly(acrylic acid) and calcium ions, resulting in hydrogel crosslinking, induces differences in Raman spectra of the hydrogel before and after the crosslinking. The crosslinking results in significant increase in the activation energy of β-relaxation of poly(acrylic acid). This is a direct consequence of restriction in motions of carboxylic groups of poly(acrylic acid) due to calcium salt formation. Thus, the crosslinking improves polymer network stability in the hydrogel in the swollen state.

Summary: Photopolymerisation of acrylic acid (AA) topoly(acrylicacid)(polyAA)inthelyotropicliquidcrystalline(LLC) phase of hydroxypropylcellulose (HPC) in the AA-water mixture, as well as the influence of mesomorphicorganisationoftheHPConthestructureofwaterwasstudied.Raman and thermo-optical analysis results reveal that thelyotropic phase of the HPC/AA-H 2 O can be used as a tem-plate system suitable for the formation of anisotropic hydro-gels. The mesomorphic organisation of the HPC/AA-H 2 OphaseispreservedafterphotopolymerisationinducedbyUVradiation. Also the structure of water, strongly disturbed intheLLC-phaseascomparedwiththestructureofliquidwater,is preserved after the photopolymerisation. Apart from thewater originating from the LLC-phase of HPC/AA-H 2 O, theanisotropichydrogelmayalsocontainwatermoleculestakenup during immersion of the hydrogel in liquid water. Ramanspectroscopy reveals that the water resulting from theswellinghasastructureclosetothatofliquidwater.Becausethe anisotropic hydrogel network is created by hydrogenbondsbetweenHPC,waterandpolyAA,itisnotstablewhenimmersedinwaterforlongtime.AnincreasedstabilityoftheLC-organisation of the hydrogel network can be achievedby crosslinking of the hydrogel with calcium ions, whichcan form a salt with polyAA, as confirmed by Ramanspectroscopy.Comparisonofthe(a)Ramanspectrumofliquidwaterwith(b)that of water in the hydrogel, illustrating the influence of themesomorphic organization in the hydrogel on the waterstructure.

The status and nature of water molecules in hydrogels with a liquid crystalline organization of the polymer network based on a biopolymer were investigated. Liquid crystalline (LC) hydrogels were obtained in situ by the photopolymerization of acrylic acid into the lyotropic liquid crystalline phase of (2-hydroxypropyl)cellulose in a solvent mixture of water and acrylic acid. The photopolymerization of acrylic acid in the lyotropic liquid crystalline phase at room temperature gives a hydrogel in which liquid crystalline order and water are retained. The liquid crystalline hydrogel contains water, which originates from the composition of the lyotropic liquid crystalline phase, and may also contain water after immersion in liquid water. The water molecule characteristics were examined by means of differential scanning calorimetry, dielectric relaxation spectroscopy, and differential scanning calorimetry coupled with thermo-optical measurements. The swelling data were obtained by using a weighing method. The investigations reveal the different nature of the two above-mentioned water types. For the water from the composition of the lyotropic liquid crystalline phase, the phase transitions—typical for the bulk water—were not observed, in contract to the water after swelling of the liquid crystalline hydrogel in the liquid water. The results of the measurements suggest that water, which comes from the composition of the lyotropic liquid crystalline phase, forms—together with a polymer network—a microstructure, stabilized by this water. The water, after swelling of the LC hydrogel in the liquid water, is separated in the pores of the hydrogel and exhibits the phase transitions of the bulk water. Copyright © 2003 John Wiley & Sons, Ltd.

Comprehensive studies of the molecular and electronic structures, vibrational frequencies, and infrared and Raman intensities of the aniline radical cation, C6H5NH2+ have been performed by using the unrestricted density functional (UB3LYP) and second-order Moller–Plesset (UMP2) methods with the extended 6-311++G(df,pd) basis set. For comparison, analogous calculations were carried out for the closed-shell neutral aniline. The studies provided detailed insight into the bonding changes that take place in aniline upon ionization. The natural bond orbital (NBO) analysis has revealed that the pπ-radical conjugative interactions are of prime importance in stabilizing the planar, quinoid-type structure of the aniline radical cation. It is shown that the natural charges calculated for aniline are consistent with the chemical properties of this molecule (an ortho- and para-directing power of the NH2 group in electrophilic substitutions), whereas Mulliken charges are not reliable. The theoretical vibrational frequencies of aniline, calculated by the B3LYP method, show excellent agreement with the available experimental data. In contrast, the MP2 method is deficient in predicting the frequencies of several modes in aniline, despite the use of the extended basis set in calculations. The frequencies of aniline radical cation, calculated at the UB3LYP/6-311++G(df,pd) level, are in very good agreement with the recently reported experimental data from zero kinetic energy photoelectron and infrared depletion spectroscopic studies. The clear- cut assignment of the IR and Raman spectra of the investigated molecules has been made on the basis of the calculated potential energy distributions. Several bands in the spectra have been reassigned. It is shown that ionization of aniline can be easily identified by the appearance of the very strong band at about 1490 cm−1, in the Raman spectrum. The redshift of the N–H stretching frequencies and the blueshift of the C–H stretching frequencies are observed in aniline, upon ionization. As revealed by NBO analysis, the frequency shifts can be correlated with the increase of electron density (ED) on the antibonding orbitals (σNH*) and decrease of ED on σCH*, respectively. These effects are associated with a weakening of N–H bonds and strengthening of C–H bonds in the aniline radical cation. The simulated theoretical Raman and infrared spectra of aniline and its radical cation, reported in this work, can be used in further spectroscopic studies of their van der Waals clusters and hydrogen bonded complexes.

We made comparison of titanium dioxide powders obtained from three syntheses including sol-gel and precipitation methods as well as using layered (tetramethyl)ammonium titanate as a source of TiO2. The obtained precursors were subjected to step annealing at elevated temperatures to transform into rutile form. The transformation was determined by Raman measurements in each case. The resulting products were characterised using Raman spectroscopy and dynamic light scattering. The main goal of the studies performed was to compare the temperature of the transformation in three titania precursors obtained by different methods of soft chemistry routes and to evaluate dielectric properties of rutile products by means of broadband dielectric spectroscopy. Different factors affecting the electrical properties of calcinated products were discussed. It was found that sol-gel synthesis provided rutile form after annealing at 850°C with the smallest particles size about 20 nm, the highest value of dielectric permittivity equal to 63.7, and loss tangent equal to 0.051 at MHz frequencies. The other powders transformed to rutile at higher temperature, that is, 900°C, exhibit lower value of dielectric permittivity and had a higher value of particles size. The correlation between the anatase-rutile transformation temperature and the size of annealed particles was proposed. This work was financially supported by the National Science Center (Poland) grant awarded by Decision no. DEC-2011/03/D/ST5/06074. The authors are grateful to Professor Adam Tracz from the Polish Academy of Science in Lodz for his help in performing SEM investigations.

The (2-hydroxypropyl)cellulose (HPC) derivatives can be regarded as a system which is composed of poly(saccharide) main chain (hydrophilic segment) and aliphatic side chain as a hydrophobic (lipophilic) segment of the macromolecules. The influence of the hydrophobic effect on the thermotropic mesomorphism of HPC derivatives was investigated. The correlation between d-spacing of HPC-derivatives estimated from X-ray measurements and hydrophobic effect of the side chain was found. The relative hydrophobicity variation of the side chains of HPC-derivatives leads to an increase in the d-spacing between poly(saccharide) main chains. On the other hand, the increasing d-spacing in the HPC-derivatives shifts their transition temperatures to isotropic state and glass transition temperatures towards lower temperature range. It was suggested that the property/structure correlation of the HPC-derivatives is affected by the balance between hydrophilic and hydrophobic parts of the HPC-derivative macromolecules.

SUMMARY: Novel anisotropic polymer composites obtained by the photopolymerisation of acrylic acid (AA) in lyotropic solutions of (2-hydroxypropyl)cellulose (HPC) were investigated. Raman spectroscopy was used in the study of hydrogen bonding formed by carboxylic groups of poly(acry1ic acid) (pAA) between themselves and with the hydroxyl groups of HPC macromolecules. These investigations show that the supramolecular structure of pAA obtained by photopolymerisation contains mainly inner oligomeric forms and cyclic dimer forms, as a consequence of the “matrix polymerisation” of AA. The presence of HPC affects the process of the photopolymerisation of AA, by a redistribution of hydrogen bonding within the system, leading to a different supramolecular structure of pAA. With increasing amounts of HPC the inner oligomeric forms characteristic of bulk pAA disappear. In the composites, the pAA chains probably form the terminal oligomeric structure, with some free COOH groups, as well as hydrogen bonds with HPC.

A new strategy for preparation of nano-sized barium titanate (BaTiO 3 ) particles was applied by using: layered (tetramethyl)ammonium titanate, barium acetate and tetramethylammonium hydroxide. An addition of barium salt to aqueous layered titanate colloids leads to a precipitation phenomenon by which barium titanate precursor was obtained. The mechanism of this reaction is based on ions exchange which permits to incorporate barium ions into titanate layers. This was confirmed by comparison of broadband dielectric spectroscopy (BDS) data of layered (tetramethyl)ammonium titanate and barium titanate precursor.

The ortho-meta-, and para-fluoro substituted anilines are prototype molecules for investigation of the interactions of both the amino group and the fluorine atom with the aromatic ring. The molecular structures, natural atomic charges and theoretical anharmonic Raman and infrared spectra of the three fluoroaniline isomers have been calculated by using the density functional B3LYP method with the extended 6-311++G(df,pd) basis set. The Raman and infrared spectra of 2FA, 3FA, and 4FA have been recorded. The detailed vibrational assignments of the experimental spectra have been made on the basis of the calculated potential energy distributions, PEDs. The effect of fluorine substituent on the aniline ring geometry and charge distribution, the nature of the characteristic “marker bands” and a quenching of intensities of some bands are discussed. It is shown that the frequencies of the NH2 stretching vibrations depend on the degree of pyramidalization of the C–NH2 group, in the isomers. In 2FA and 3FA, the NH2 stretching frequencies are higher than those in 4FA. This corresponds to a more flattened structure of the amino group in 2FA and 3FA, in comparison to 4FA.

Biphalin (0.3 mg/kg) administered intravenously (i.v.) to urethane-chloralose anaesthetized rats consistently evoked apnoea, followed by breathing at subnormal respiratory rate with increased tidal volume. Mean arterial pressure and heart rate were lowered. Naloxone completely antagonized the respiratory and cardiovascular responses to biphalin. Midcervical vagotomy prevented all respiratory effects of biphalin, and nearly abolished the fall in blood pressure and attenuated bradycardia. These results indicate that mu opioid receptors distributed in areas supplied by vagal afferents (e.g. the lung) are involved in respiratory and hypotensive effects of biphalin, whereas bradycardia may be explained by activation of brainstem regions mediating cardiovascular control.

The theoretical IR and Raman spectra of para -halogenoanilines, 4-XC 6 H 4 NH 2 (X = F, Cl and Br) were calculated by using the density functional B3LYP method with the 6-311++G(df,pd) basis set. The theoretical spectra show very good agreement with experiment. The rigorous normal coordinate analyses have been performed, and the detailed vibrational assignment has been made on the basis of the calculated potential energy distributions (PEDs). Several ambiguities and contradictions in the previously reported vibrational assignments have been clarified. The “marker bands” and the effects of the halogen substituent on the characteristic aniline bands in the IR and Raman spectra are discussed.

The water structure existing in (2-hydroxypropyl)cellulose-poly(acrylic acid)-water (HPC-PAA-H2O) hydrogel, exhibiting liquid crystalline (LC) organization of the polymer network (anisotropic hydrogel), was assessed by means of Raman spectroscopy. It was shown that the LC-network of HPC-PAA-H20 exerts significant influence on the structure of liquid water present in the hydration shells around polymer chains of the anisotropic hydrogel. Due to poor stability of LC-ordering of polymer network, observed in HPC-PAA-H2O) after its long-term water immersion, the process of crosslinking of the anisotropic hydrogel was considered. The results of Raman measurements revealed that, during immersion of HPC-PAA-H2O in calcium ions (Ca2+) solution, formation of a salt by poly(acrylic acid) of HPC-PAA-H2O and Ca2+ takes place. This results in crosslinking of the anisotropic hydrogel, leading -- in a consequence -- to significant improvement of its mechanical toughness, as well as to stability of LC-ordering of the investigated network in the swollen state. However, during crosslinking of the anisotropic hydrogel (by Ca2+), apart from formation of the salt by Ca2+ and PAA, the ions influence additionally the structure of the water existing in hydration shells round polymer chains of both polymer constituents (HPC and PAA) creating the anisotropic hydrogel network.© (2004) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Mesomorphism and photocuring processes of (2- hydroxypropyl)cellulose cinnamate (CYPC) were investigated. The CYPC was synthesized in the course of estrification of (2-hydroxypropyl)cellulose (HPC) by cinnamoyl chloride. The chemical structure of CYPC was confirmed by IR and Raman spectroscopy. The substitution degree of HPC by cinnamoyl ester groups was calculated from 1 H-NMR studies. The thermotropic mesomorphism of CYPC was confirmed by DSC, thermo-optical and X-ray investigations. The thermo-optical behaviors of CYPC tablet obtained under pressure and results of the dielectric spectroscopy investigations were interpreted in terms of the strong hydrophobic effect of the cinnamoyl ester groups. The cycloaddition of the cinnamoyl groups is initiated either by UV radiation or temperature, inside of the hydrophobic aggregates of the cinnamoyl ester groups. The chemical modification of the hydrophobic aggregates in the course of thermo- or photoaddition of the cinnamoyl ester groups slightly changes a molecular movement of the poly(saccharide) main chains of CYPC. However, these crossed aggregates can recover macromolecular orientation of CYPC from the isotropic state via the cooling of sample. These suggest that the hydrophobic aggregates after thermal or photochemical modification shows an anisotropic behavior.

A two-stage method of synthesis of liquid-crystalline diepoxy monomers has been developed. In the first stage, esterification of 4-hydroxyphenyl-4-hydroxybenzoate or 4,4'- biphenol or 4,4'-dihydroxyazobenzene was carried out using 4-penetenoic acid. The resulting olefinic precursors were oxidized with m-chloroperoxybenzoic acid to introduce the epoxy groups. The structure of products was confirmed by FT- IR and 1 H NMR. Examinations on a polarization microscope with a hot plate confirmed the presence of mesomorphic phases in both the precursors and monomers. The phase transition temperatures were in the range of 73.5 (at cooling) to 128.0 degree(s)C for olefinic precursors and in the range 57.1 (at cooling) to 143 degree(s)C for epoxy compounds, as determined by DSC and thermo-optical analysis (TOA).

An elaborate computer program to simulate the process of starch hydrolysis by amylolytic enzymes was been developed. It is based on the Monte Carlo method and iteration kinetic model, which predict productive and non-productive amylase complexes with substrates. It describes both multienzymatic and multisubstrate reactions simulating the "real" concentrations of all components versus the time of the depolymerization reaction the number of substrates, intermediate products, and final products are limited only by computer memory. In this work, it is assumed that the "proper" substrate for amylases is the glucoside linkages in starch molecules. Dynamic changes of substrate during the simulation adequately influence the increase or decrease of reaction velocity, as well as the kinetics of depolymerization. The presented kinetic model, can be adapted to describe most enzymatic degradations of a polymer. This computer program has been tested on experimental data obtained for alpha- and beta-amylases.

The microstructure of the polymer composite based on the LC- cellulose derivative and poly(acrylonitrile) was investigated. The polymer composite was obtained by photopolymerization of the mechanically oriented (shearing) lyotropic LC-solution of the (2-hydroxypropyl)cellulose (HPC) in the acrylonitrile (AN). The use of multiple techniques: dielectric, thermogravimetric, mass spectroscopies, and thermooptical analysis enabled to overcome resolution problem related to behavior of the non- mesogenic polymer network of poly(acrylonitrile) in the mesogenic environment of the HPC. The results of the investigation of the composite microstructure show that the polymer composite is composed of two subsystems: mesogenic system of cellulose derivative and oriented fibril-like polymer network which is formed by non-mesogenic poly(AN). The polymer network of poly(AN) influences the optical anisotropy relaxation of the mesogenic HPC in the composite.

New aspects of cellulosic material science and application are related to the lyotropic liquid crystalline properties of this classical natural polymer. In this work the preparation of anisotropic polymer networks based on (hydroxypropyl) cellulose and its derivatives as well as their properties are discussed. Cellulose derivatives form liquid crystalline solutions also in polymerizable solvents, e.g. acrylic acid thus anisotropic polymeric networks can be fixed by photopolymerization. These films have been investigated with regard to their orientation birefringence and thermal stability. Some possible applications of these interesting systems are briefly shown.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Cellulose derivatives have been shown to form liquid crystalline solutions at high polymer concentration ina wide range organic solvents. This paper describes the liquid crystalline behaviour of the cellulose derivativessuspended in uv-curable polyester resin. The diffusion phenomena of the acetic acid and methanol to cellulosedomain suspended in uv-curable liquid polyester resin were used, for obtaining crystalline phase. The sampleswere investigated by thermo-optical, light and x-ray scattering methods.1. INTRODUCTION.Over the past decade liquid crystalline solution (LCs) of cellulose derivatives have received a considerableamount of attention. The first published repoif showed that concentrated aqueous solution of hydroxypropyl cellulose (HPC) formed a cholesteric liquid crystalline phase. Many other cellulose derivatives have been shown to form LCs in a wide variety of soIvents. The liguid crystalline phase was in most cases determined to becholesteric. The formation of the liquid crystalline phase was shown to be strongly dependent of polymerconcentration, solvent type and temperature?. The formation of the ordered phase is attributed to the limitedflexibility of the cellulose chain. However, some cellulose derivatives form liquid crystalline phases only inspecific solvents. Concentrated solutions in other solvents remain isotropic. It has been suggested that the role

Chimerization of tachykinin and opioid pharmacophores offers a new avenue for analgesic development. The complexities of such design are illustrated by the analgesic efficacy (via different mechanisms) of chimeras that combine pharmacophores with opioid activity and substance P activity, as well as those that combine opioid agonist and substance P antagonist moieties. Although the interaction between substance P and opioid neural systems is more complex than a simple one-way inhibition, the relative balance of activities between tachykinin and opioid pharmacophores will generally determine the net effect of the chimeric molecule as pro-nociceptive, antinociceptive, or neutral. Intriguingly, endomorphins—μ-opioid receptor agonists with high intrinsic activity—may owe some of this high activity to weak but significant antagonist proper ties at tachykinin NK2 receptors, implying that these native peptides are endogenous chimeric opioid agonist–tachykinin antagonist compounds.

The birefringence of anisotropic polymer composites obtained by photopolymerisation of lyotropic liquid crystalline systems composed of (hydroxypropyl)cellulose derivatives (R-PC) and photopolymerisable organic acids that are also lyotropic solvents is studied. The orientation of the systems before photopolymerisation was induced by shearing. The mechanically oriented lyotropic solutions after cessation of shearing form a band texture visible under crossed polarisers. This band texture shows relaxation phenomena and the grain texture observed before shearing recovers with time. The decay time of the relaxation of the band texture at room temperature is much longer than the time of band texture formation after cessation of shearing. The photopolymerisation of acrylic acid (or methacrylic acid) in the oriented R-PC/acid lyotropic solutions leads to birefringent polymer composites. These composites show reversible anisotropic optical properties as examined by thermo-optical analysis (In contrast with the samples before photopolymerisation); therefore they can be classified as reversible anisotropic polymer networks. It is demonstrated that the thermal stability of the birefringence of the R-PC/poly(acid) composites is mainly determined by the molecular mobility of the poly(acid) connected with its glass transition temperature.