Chitosan-based mucoadhesive tablets for oral delivery of ibuprofen

Chitosan and its half-acetylated derivative have been compared as excipients in mucoadhesive tablets containing ibuprofen. Initially the powder formulations containing the polymers and the drug were prepared by either co-spray drying or physical co-grinding. Polymer-drug interactions and the degree of drug crystallinity in these formulations were assessed by infrared spectroscopy and differential scanning calorimetry. Tablets were prepared and their swelling and dissolution properties were studied in media of various pHs. Mucoadhesive properties of ibuprofen-loaded and drug-free tablets were evaluated by analysing their detachment from pig gastric mucosa over a range of pHs. Greater polymer-drug interactions were seen for spray-dried particles compared to co-ground samples and drug loading into chitosan-based microparticles (41%) was greater than the corresponding half-acetylated samples (32%). Swelling and drug release was greater with the half-acetylated chitosan tablets than tablets containing the parent polymer and both tablets were mucoadhesive, the extent of which was dependent on substrate pH. The results illustrate the potential sustained drug delivery benefits of both chitosan and its half-acetylated derivative as mucoadhesive tablet excipients.     

An affective computing approach to physiological emotion specificity: toward subject-independent and stimulus-independent classification of film-induced emotions

The hypothesis of physiological emotion specificity has been tested using pattern classification analysis (PCA). To address limitations of prior research using PCA, we studied effects of feature selection (sequential forward selection, sequential backward selection), classifier type (linear and quadratic discriminant analysis, neural networks, k-nearest neighbors method), and cross-validation method (subject- and stimulus-(in)dependence). Analyses were run on a data set of 34 participants watching two sets of three 10-min film clips (fearful, sad, neutral) while autonomic, respiratory, and facial muscle activity were assessed. Results demonstrate that the three states can be classified with high accuracy by most classifiers, with the sparsest model having only five features, even for the most difficult task of identifying the emotion of an unknown subject in an unknown situation (77.5%). Implications for choosing PCA parameters are discussed.     

Energy Structure and Luminescence of CeF3 Crystals

The results of the calculation of the energy band structure and luminescent research of CeF₃ crystals are presented. The existence of two 5d1 and 5d2 subbands of the conduction band genetically derived from 5d states of Ce³⁺ ions with different effective electron masses of 4.9 m_e and 0.9 m_e, respectively, is revealed. The large electron effective mass in the 5d1 subband facilitates the localization of electronic excitations forming the 4f-5d cerium Frenkel self-trapped excitons responsible for the CeF₃ luminescence. The structure of the excitation spectra of the exciton luminescence peaked at 290 nm, and the defect luminescence at 340 nm confirms the aforementioned calculated features of the conduction band of CeF₃ crystals. The peculiarities of the excitation spectra of the luminescence of CaF₂:Ce crystals dependent on the cerium concentration are considered with respect to the phase formation possibility of CeF₃.     

Medical management of spontaneous celiac artery dissection: case report and literature review

Spontaneous visceral artery dissections are a rare occurrence. Here we report a case of spontaneous celiac artery dissection that was treated without surgery.     

Intracerebroventricular infusion of CRF increases extracellular concentrations of norepinephrine in the hippocampus and cortex as determined by in vivo voltammetry

Previous studies have indicated that intracerebroventricular (i.c.v.) infusions of corticotropin-releasing factor (CRF) activate locus coeruleus (LC) noradrenergic neurons and increase the metabolism and extracellular concentrations of norepinephrine (NE) in several brain regions, suggesting increased release. To examine the temporal aspects and mechanism of the presumed release of NE, CRF was infused i.c.v. and the oxidation current was recorded using carbon fiber voltammetric electrodes placed in rat hippocampus or cortex. The CRF (1 μg, i.c.v.) caused a significant increase of oxidation current with a delay of approximately 5 min, and a peak at approximately 35 min. Similar responses were observed in the medial prefrontal cortex. The hippocampal response was markedly attenuated when CRF was infused into rats pretreated with DSP-4 to deplete NE, suggesting that the observed changes in current resulted from oxidation of NE. The increase of NE-like current did not occur when 25 μg alpha-helical CRF_9–41 (ahCRF) was injected immediately before 1 μg CRF, suggesting that the response was mediated by cerebral CRF-receptors. Subcutaneous pretreatment with the ganglionic blocker, chlorisondamine, at a dose of 3 mg/kg had no effect on the voltammetric response to CRF, but a 6 mg/kg dose completely prevented the response. The β-adrenoceptor antagonists, S-propranolol (5 mg/kg), nadolol (5 and 10 mg/kg), and timolol (5 mg/kg) attenuated the NE response to i.c.v. CRF to varying degrees. When chlorisondamine (3 μg) or nadolol (5 μg) were given i.c.v. before the CRF, the hippocampal responses were not blocked. These results suggest peripheral actions of ganglionic and β-adrenergic blockers. We conclude that peripheral autonomic mechanisms, and probably both central and peripheral β-adrenoceptors, contribute to the increased secretion of hippocampal NE in response to i.c.v. CRF.     

A decisive role of mitochondria in defining rate and intensity of apoptosis induction by different alkaloids

Sanguinarine, chelerythrine and chelidonine possess prominent apoptotic effects towards cancer cells. In this study, we found that sanguinarine and chelerythrine induce apoptosis in human CEM T-leukemia cells, and that is accompanied by an early increase in cytosolic cytochrome c that precedes caspases-8, -9 and -3 processing. During apoptosis induction by sanguinarine and chelerythrine, reactive oxygen species (ROS) was rapidly generated and DeltaPsi(mt) dissipated, while Bax, Bcl-2 and Bcl-X((L/S)) proteins' content in the mitochondrial fraction did not change significantly. Caspase-3 activation and DNA fragmentation were considerably inhibited by N-acetyl-cysteine (NAC). Chelidonine induced only a slight release of cytochrome c (12h), parallel to caspase-3 activation. Effect of sanguinarine or chelerythrine towards mitochondria was confirmed by marked changes in morphology of this organelle (3h), while chelidonine did not affect mitochondria intactness. Sanguinarine or chelerythrine also caused an intensive DNA damage in cells in 1h, however a massive increase in number of such impaired cells occurred in 6h, while chelidonine induced intensive DNA damage in 15-20% cells only in 24h. Thus, our results demonstrated that rapid cytochrome c release in CEM T-leukemia cells exposed to sanguinarine or chelerythrine was not accompanied by changes in Bax, Bcl-2 and Bcl-X((L/S)) proteins in the mitochondrial fraction, and preceded activation of the initiator caspase-8.     

College of American Pathologists Tumor Regression Grading System for Long-Term Outcome in Patients with Locally Advanced Rectal Cancer

BackgroundThe National Comprehensive Cancer Network''s Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined.Materials and MethodsThis was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease‐free survival (DFS), local recurrence‐free survival (LRFS), and distant metastasis‐free survival (DMFS) were assessed by Kaplan‐Meier analysis, log‐rank test, and Cox regression model.ResultsThe discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1–3 cases, adjuvant chemotherapy treatment significantly improved 3‐year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate.ConclusionAJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC.Implications for PracticeThe National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four‐category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long‐term survival outcome. Importantly, adjuvant chemotherapy may improve the 3‐year overall survival for AJCC/CAP TRG1–3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long‐term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.     

On the transmit field inhomogeneity correction of relaxation‐compensated amide and NOE CEST effects at 7 T

High field MRI is beneficial for chemical exchange saturation transfer (CEST) in terms of high SNR, CNR, and chemical shift dispersion. These advantages may, however, be counter‐balanced by the increased transmit field inhomogeneity normally associated with high field MRI. The relatively high sensitivity of the CEST contrast to B₁ inhomogeneity necessitates the development of correction methods, which is essential for the clinical translation of CEST. In this work, two B₁ correction algorithms for the most studied CEST effects, amide‐CEST and nuclear Overhauser enhancement (NOE), were analyzed. Both methods rely on fitting the multi‐pool Bloch‐McConnell equations to the densely sampled CEST spectra. In the first method, the correction is achieved by using a linear B₁ correction of the calculated amide and NOE CEST effects. The second method uses the Bloch‐McConnell fit parameters and the desired B₁ amplitude to recalculate the CEST spectra, followed by the calculation of B₁‐corrected amide and NOE CEST effects. Both algorithms were systematically studied in Bloch‐McConnell equations and in human data, and compared with the earlier proposed ideal interpolation‐based B₁ correction method. In the low B₁ regime of 0.15–0.50 μT (average power), a simple linear model was sufficient to mitigate B₁ inhomogeneity effects on a par with the interpolation B₁ correction, as demonstrated by a reduced correlation of the CEST contrast with B₁ in both the simulations and the experiments.     

Pre‐ to postsleep change in psychophysiological reactivity to emotional films: Late‐night REM sleep is associated with attenuated emotional processing

Rapid eye movement (REM) sleep has been postulated to facilitate emotional processing of negative stimuli. However, empirical evidence is mixed and primarily based on self‐report data and picture‐viewing studies. This study used a full‐length aversive film to elicit intense emotion on one evening, and an emotionally neutral control film on another evening while psychophysiological and experiential responses were measured. Subsequent sleep was monitored polysomnographically, and specific film scenes were presented again on the next morning. Correlation analyses revealed that participants with longer late‐night REM sleep after the aversive film showed higher increase of electrodermal reactivity and less reduction of facial corrugator muscle reactivity to negative film scenes on the next morning. This indicates that REM sleep may be associated with attenuated emotional processing of prolonged and intense emotional stimuli from pre‐ to postsleep.