In situ sono-rheometric assessment of procaine-loaded calcium pectinate hydrogel for enhanced drug releasing under ultrasound stimulation.

Ultrasound (US) triggered alterations in the viscoelastic behavior of the procaine-loaded ionically gelatinized pectin hydrogel matrix, and drug release was observed using a sono-device rheometer. The gel softened immediately upon activation of the ultrasound operated at 43 kHz and remained in a softened state throughout the irradiation. Upon cessation of ultrasound, the gel promptly reverted to its original hardness. This cycle of softening was consistently observed in ionically crosslinked pectin hydrogels, resulting in the promotion of procaine release, particularly with higher US power and lower calcium concentration. As the amount of loaded procaine increased, the gel weakened due to ion exchange with the calcium crosslinker and procaine. The most substantial release efficiency, reaching 82 % with a concentration of 32 µg/ml, was achieved when the hydrogels contained 0.03 % procaine within the gelatinized hydrogel medicine at a calcium concentration of 0.9 M, representing a six-fold increase compared to that without US. Notably, US exposure affected the 3D porous structure and degradation rate, leading to hydrogel collapse and facilitating medicine release. Additionally, the procaine-loaded pectin hydrogels with 0.9 M calcium exhibited improved fibroblast cell viability, indicating non-toxicity compared to those hydrogels prepared at a higher Ca2+ concentration of 2.4 M.

Ultrasound-Triggered Amoxicillin Release from Chitosan/Ethylene Glycol Diglycidyl Ether/Amoxicillin Hydrogels Having a Covalently Bonded Network.

An antibiotic release system triggered by ultrasound (US) was investigated using chitosan (CS)/ethylene glycol diglycidyl ether (EGDE) hydrogel carriers with amoxicillin (Amox) drug. Different CS concentrations of 1.5, 2, 2.5, and 3 wt % were gelled with EGDE and Amox was entrapped in the hydrogel carrier; the accelerated release was observed as triggered by 43 kHz US exposure at different US output powers ranging from 0 to 35 W. Among these CS hydrogel systems, the degree of accelerated Amox release depended on the CS concentration for the hydrogelation and the matrix with 2 wt % CS exhibited efficient Amox release at 35 W US power with around 19 µg/mL. The drug released with time was fitted with Higuchi and Korsmeyer-Peppas models, and the enhancement was caused by US aiding drug diffusion within the hydrogel matrix by a non-Fickian diffusion mechanism. The US effect on the viscoelasticity of the hydrogel matrix indicated that the matrix became somewhat softened by the US exposure to the dense hydrogels for 2.5 and 3% CS/EGDE, while the degree of softening was slightly marked in the CS/EGDE hydrogels prepared with 1.5 and 2% CS concentration. Such US softening also aided drug diffusion within the hydrogel matrix, suggesting an enhanced Amox release.

Needs Analysis About Intercultural Communicative Competence Among Undergraduate Tourism Students.

With both the quantitative and qualitative data from 628 responses to a set of questionnaire collected from the undergraduates of three educational institutions in central Vietnam, this study analyzed learners' needs of intercultural communication competence (ICC) related to their studying of English for tourism purposes and future occupations. The methodology used for data analysis including semi-structured interviews, and the questionnaire. The findings showed that the students preferred intercultural language learning activities referring to authentic materials and real-life experience. The results also revealed the participants' great needs of various ICC attitudes and regular tasks in tourism workplaces. Particularly, they had positive attitudes in intercultural communication, and higher needs of tasks for improving discourse and behavioural competences more than other ICC dimensions. The study has implications for tourism learners, educators and related stakeholders to raise their awareness in learning, teaching and developing this long-lasting competence.

Viscoelastic Analysis of Pectin Hydrogels Regenerated from Citrus Pomelo Waste by Gelling Effects of Calcium Ion Crosslinking at Different pHs.

Pectin was extracted from citrus pomelo waste, and the effects of calcium ions (Ca2+) on the gelation and hydrogels properties were investigated over a pH range of 3.2-8 by using viscoelastic analysis. The gelatinization of Ca2+-pectin was examined at concentrations of 0.9, 1.8, 2.4, and 3.6 M of Ca2+ in aqueous pectin solutions of 1%, 2%, 3%, and 4%. The gel transition of Ca2+-pectin solution to hydrogels was determined by measuring the storage modulus (G') and loss modulus (G") under mechanical strain from 0.01 to 100%. In a hydrogel of 3% pectin at Ca2+ = 2.4 M, as pH increased to 7, the G' at 0.01 strain % was 3 × 104 Pa, and 3 × 103 Pa at pH 5, indicating that the crosslinking weakened at acidic pH. Due to the crosslinking between the calcium ions and the ionized carboxylic acid groups of pectin, the resulting hydrogel became stiff. When the mechanical strain % was in the range of 0.01-1%, G' was unchanged and G" was an order of magnitude smaller than G', indicating that the mechanical stress was relieved by the gel. In the range of 1-100%, the gel deformation progressed and both the moduli values were dropped. Collapse from the gel state to the solution state occurred at 1-10 strain %, but the softer hydrogels with G' of 103 Pa had a larger strain % than the stiffer hydrogels with G' of 104 Pa.

Characterization of pH-responsive high molecular-weight chitosan/poly (vinyl alcohol) hydrogel prepared by gamma irradiation for localizing drug release.

pH-sensitive hydrogels prepared by gamma irradiation find promising biological applications, partially, in the field of localized drug liberation. Herein, optimal conditions for fabricating high-molecular-weight chitosan/polyvinyl alcohol hybrid hydrogels using gamma irradiation at 10, 25, and 30 kGy were investigated by studying the water uptake behavior, the pore size on the surface, and thermal stability. Furthermore, the crosslinking mechanism of irradiated hydrogels was examined via solid-state 13C NMR spectrum. The swelling ratio of the gamma-irradiated CS/PVA hydrogel was pH-dependent; particularly, the hybrid hydrogel exhibited high swelling ratios under acidic conditions than those under basic conditions due to the protonation of amino groups on CS-backbone in acidic environments. In addition, amoxicillin was used as a model drug in the in vitro drug release investigations in pH-simulated gastric fluid and deionized water at 37 °C. To identify the drug release mechanism, several kinetic models composing zero-order, first-order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas models were used. The findings suggested that drug release is mediated by a non-Fickian transport mechanism.

2D-quantitative structure-activity relationships model using PLS method for anti-malarial activities of anti-haemozoin compounds.

BACKGROUND: Emergence of cross-resistance to current anti-malarial drugs has led to an urgent need for identification of potential compounds with novel modes of action and anti-malarial activity against the resistant strains. One of the most promising therapeutic targets of anti-malarial agents related to food vacuole of malaria parasite is haemozoin, a product formed by the parasite through haemoglobin degradation. METHODS: With this in mind, this study developed two-dimensional-quantitative structure-activity relationships (QSAR) models of a series of 21 haemozoin inhibitors to explore the useful physicochemical parameters of the active compounds for estimation of anti-malarial activities. The 2D-QSAR model with good statistical quality using partial least square method was generated after removing the outliers. RESULTS: Five two-dimensional descriptors of the training set were selected: atom count (a_ICM); adjacency and distance matrix descriptor (GCUT_SLOGP_2: the third GCUT descriptor using atomic contribution to logP); average total charge sum (h_pavgQ) in pKa prediction (pH = 7); a very low negative partial charge, including aromatic carbons which have a heteroatom-substitution in "ortho" position (PEOE_VSA-0) and molecular descriptor (rsynth: estimating the synthesizability of molecules as the fraction of heavy atoms that can be traced back to starting material fragments resulting from retrosynthetic rules), respectively. The model suggests that the anti-malarial activity of haemozoin inhibitors increases with molecules that have higher average total charge sum in pKa prediction (pH = 7). QSAR model also highlights that the descriptor using atomic contribution to logP or the distance matrix descriptor (GCUT_SLOGP_2), and structural component of the molecules, including topological descriptors does make for better anti-malarial activity. CONCLUSIONS: The model is capable of predicting the anti-malarial activities of anti-haemozoin compounds. In addition, the selected molecular descriptors in this QSAR model are helpful in designing more efficient compounds against the P. falciparum 3D7A strain.

Skeletal muscle growth dynamics and the influence of first-feeding diet in Atlantic cod larvae (Gadus morhua L.).

Dynamics between hypertrophy (increase in cell size) and hyperplasia (increase in cell numbers) of white and red muscle in relation to body size [standard length (SL)], and the influence of the first-feeding diets on muscle growth were investigated in Atlantic cod larvae (Gadus morhua). Cod larvae were fed copepod nauplii or rotifers of different nutritional qualities from 4 to 29 days post hatching (dph), Artemia nauplii from 20 to 40 dph and a formulated diet from 36 to 60 dph. The short period of feeding with cultivated copepod nauplii had a positive effect on both muscle hyperplasia and hypertrophy after the copepod/rotifer phase (19 dph), and a positive long term effect on muscle hypertrophy (60 dph). The different nutritional qualities of rotifers did not significantly affect muscle growth. We suggest here a model of the dynamics between hyperplasia and hypertrophy of red and white muscle fibre cells in relation to cod SL (4 to 30 mm), where the different red and white muscle growth phases clearly coincided with different metamorphosis stages in cod larvae. These shifts could be included as biomarkers for the different stages of development during metamorphosis. The main dietary muscle effect was that hypertrophic growth of red muscle fibres was stronger in cod larvae that were fed copepods than in larvae that were fed rotifers, both in relation to larval age and size. Red muscle fibres are directly involved in larval locomotory performance, but may also play an important role in the larval myogenesis. This can have a long term effect on growth potential and fish performance.

Live feed is not a major determinant of the microbiota associated with cod larvae (Gadus morhua).

The gastrointestinal (GI) tract of newly hatched fish is probably colonized by bacteria present in the water, but how environmental and internal factors affect the development of the GI microbiota is poorly understood. In this study, we investigated the effect of diet and of rearing in separate tanks on the cod larval microbiota. Cod larvae were fed three different live feed diets. For each diet, larvae were reared in three replicate tanks. The microbial communities were investigated for water, live feed and individual larvae using a PCR/DGGE (Denaturing Gradient Gel Electrophoresis) strategy. Statistical tests were applied to investigate differences in the larval microbiota between groups of individuals. We found no differences in the larval microbiota due to diet after 8 dph (days post hatching). Moreover, the larval microbiota was similar at 17 and 32 dph, despite a change in live feed at 18 dph. The larval microbiota was generally more similar to the water microbiota than to live feed microbiota. We further found that rearing of larvae in replicate tanks with identical diet could result in significant differences in larval microbiota. These findings indicate that diet does not entail major changes to the composition of cod larval microbiota.

An evaluation of the DRI-ETG EIA method for the determination of ethyl glucuronide concentrations in clinical and post-mortem urine.

A commercial enzyme immunoassay for the qualitative and semi-quantitative measurement of ethyl glucuronide (EtG) in urine was evaluated. Post-mortem (n=800), and clinical urine (n=200) samples were assayed using a Hitachi 902 analyzer. The determined concentrations were compared with those obtained using a previously published liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of EtG and ethyl sulfate. Using a cut-off of 0.5 µg/ml and LC-MS/MS limit of reporting of 0.1 µg/ml, there was a sensitivity of 60.8% and a specificity of 100% for clinical samples. For post-mortem samples, sensitivity and specificity were 82.4% and 97.1%, respectively. When reducing the cut-off to 0.1 µg/ml, the sensitivity and specificity were 83.3% and 100% for clinical samples whereas for post-mortem samples the sensitivity and specificity were 90.3 % and 88.3 %, respectively. The best trade-offs between sensitivity and specificity for LC-MS/MS limits of reporting of 0.5 and 0.1 µg/ml were achieved when using immunoassay cut-offs of 0.3 and 0.092 µg/ml, respectively. There was good correlation between quantitative results obtained by both methods but analysis of samples by LC-MS/MS gave higher concentrations than by enzyme immunoassay (EIA), with a statistically significant proportional bias (P<0.0001, Deming regression) for both sample types. The immunoassay is reliable for the qualitative and semi-quantitative presumptive detection of ethyl glucuronide in urine.

Validated method for the determination of ethylglucuronide and ethylsulfate in human urine.

Detection of the alcohol metabolites ethylglucuronide (EtG) and ethylsulfate (EtS) has become routine in many forensic laboratories over the last few years. Most previously published methods using liquid chromatography coupled with electrospray tandem mass spectrometry require a post-chromatographic addition of solvent and/or extensive sample preparation prior to analysis. The aim of the study was to develop a simplified method. To 20 µL urine, internal standard containing EtG-d5 and EtS-d(5) was added and the mixture was treated with elution buffer internal standard. EtG and EtS were separated using a Shimadzu Prominence high performance liquid chromatography (HPLC) system with a C18 separation column (Restek Ultra Aqueous C18, 4.6 × 150 mm, 5 µm), using isocratic elution with a mobile phase consisting of 10 mM ammonium acetate buffer pH 7 (total run time, 6 min). The compounds were detected using an Applied Biosystems API 5000 liquid chromatography tandem mass spectrometry system (atmospheric pressure chemical ionization, multiple-reaction monitoring mode). The method was fully validated according to international guidelines. The assay was found to be selective for the compounds of interest. It was linear from 0.1 to 10 mg/L for all analytes (R(2) > 0.99). Matrix effects studies showed the presence of a slight but consistent ion enhancement (n = 10 different urine samples) at low concentrations and no effects at higher concentrations. Accuracy data were between 0.75% and 8.1% bias for EtG and between -5.0% and -11.3% bias for EtS. Precision data were between 4.3% and 6.9% relative standard deviations (RSD) for EtG and between 6.0% and 7.5% RSD for EtS. No instability was observed after repeated freezing and thawing. This fast, reliable, and accurate method enables the detection and quantification of alcohol metabolites in urine. The method is easier to use and more sensitive than previously published methods.