Hydrogels are very attractive materials due to their multifunctional properties. Many natural polymers, such as polysaccharides, are used for the preparation of hydrogels. The most important and ...commonly used polysaccharide is alginate because of its biodegradability, biocompatibility, and non-toxicity. Since the properties of alginate hydrogel and its application depend on numerous factors, this study aimed to optimize the gel composition to enable the growth of inoculated cyanobacterial crusts for suppressing the desertification process. The influence of alginate concentration (0.1-2.9%, m/v) and CaCl
concentration (0.4-4.6%, m/v) on the water-retaining capacity was analyzed using the response surface methodology. According to the design matrix, 13 formulations of different compositions were prepared. The water-retaining capacity was defined as the system response maximized in optimization studies. The optimal composition of hydrogel with a water-retaining capacity of about 76% was obtained using 2.7% (m/v) alginate solution and 0.9% (m/v) CaCl
solution. Fourier transform infrared spectroscopy was used for the structural characterization of the prepared hydrogels, while the water content and swelling ratio of hydrogels were determined using gravimetric methods. It was concluded that alginate and CaCl
concentrations play the most important role regarding the gelation time, homogeneity, water content, and swelling ratio of the hydrogel.
This paper aimed to optimize the extraction of antioxidants from plum seeds (
Prunus domestica
L.) using ultrasound-assisted extraction. The Box–Behnken design was used for the optimization of the ...extraction process. The four extraction parameters, such as the extraction time (10–40 min), ethanol concentration (20–100%, v/v), liquid-to-solid ratio (10–30 cm
3
g
−1
), and extraction temperature (30–70 °C) were varied to investigate their impact on the content of antioxidants. Using HPLC methods, the following phenolic compounds were identified and quantified per 100 g dry weight: rutin (6.39 mg), epigallocatechin (1.94 mg), gallic acid (0.64 mg), ferulic acid (14.30 mg), syringic acid (0.87 mg), epicatechin (0.95 mg), caffeic acid (0.30 mg), and coumaric acid (11.18 mg). The content of amygdalin was 1.5 mg g
−1
of the dry extract obtained under optimal conditions. Antioxidant activity was determined using the DPPH assay and estimated based on the half-maximal inhibitory concentration (IC
50
). The IC
50
value of the extract obtained under optimal conditions was 0.94 mg cm
−3
. The proposed green technique is an economical and alternative procedure for the extraction of antioxidants by application of non-toxic and eco-friendly solvents. From the ecological point of view, it is acceptable due to the reduction of waste either after plum cultivation or production of alcoholic beverages.
The paper was aimed at developing an ultrasound-assisted extraction of carotenoids from orange peel using olive oil as a solvent. A central composite design was used to define the optimal conditions ...for their extraction. Under the optimal conditions (extraction time of 35 min, extraction temperature of 42 ℃, and a liquid-to-solid ratio of 15 mL/g), the experimental and predicted values of carotenoid content were 1.85 and 1.83 mg/100 g dry weight, respectively. The agreement of these values indicated the adequacy of the proposed regression model. The extraction temperature only had a negative influence on carotenoid content. The impact of extraction parameters on the carotenoid content was decreased according to the following order: extraction time, liquid-to-solid ratio, and extraction temperature. Ca-alginate beads were prepared using the extrusion process to increase the stability and protect the antioxidant activity of olive oil enriched with carotenoids. The encapsulation efficiency and particle mean diameter were 89.5% and 0.78 mm, respectively. The presence of oil extract in Ca-alginate beads was confirmed by Fourier-transform infrared spectroscopy. The antioxidant activity of the oil enriched with carotenoids before and after encapsulation in the alginate beads was determined according to the DPPH assay.
Reducing natural resources caused by the growth of the world’s population, meeting the growing demands of consumers, and preventing environmental pollution requires the development of sustainable and ...efficient procedures that include the valorization of wastes ...
This study aimed to improve the conventional procedure of alginate isolation from the brown seaweed (Laminaria digitata L.) biomass and investigate the possibility of further valorization of the ...ethanolic fraction representing the byproduct after the degreasing and depigmentation of biomass. The acid treatment of biomass supported by ultrasound was modeled and optimized regarding the alginate yield using a response surface methodology based on the Box–Behnken design. A treatment time of 30 min, a liquid-to-solid ratio of 30 mL/g, and a treatment temperature of 47 °C were proposed as optimal conditions under which the alginate yield related to the mass of dry biomass was 30.9%. The use of ultrasonic radiation significantly reduced the time required for the acid treatment of biomass by about 4 to 24 times compared to other available conventional procedures. The isolated alginate had an M/G ratio of 1.08, which indicates a greater presence of M-blocks in its structure and the possibility of forming a soft and elastic hydrogel with its use. The chemical composition of the ethanolic fraction including total antioxidant content (293 mg gallic acid equivalent/g dry weight), total flavonoid content (14.9 mg rutin equivalent/g dry weight), contents of macroelements (the highest content of sodium, 106.59 mg/g dry weight), and microelement content (the highest content of boron, 198.84 mg/g dry weight) was determined, and the identification of bioactive compounds was carried out. The results of ultra high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry analysis confirmed the presence of 48 compounds, of which 41 compounds were identified as sugar alcohol, phenolic compounds, and lipids. According to the 2,2-diphenyl-1-picrylhydrazyl assay, the radical scavenging activity of the ethanolic fraction (the half-maximal inhibitory concentration of 42.84 ± 0.81 μg/mL) indicated its strong activity, which was almost the same as in the case of the positive control, synthetic antioxidant butylhydroxytoluene (the half-maximal inhibitory concentration of 36.61 ± 0.79 μg/mL). Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, and Bacillus cereus) were more sensitive to the ethanolic fraction compared to Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Shigella sonnei). The obtained results indicated the possibility of the further use of the ethanolic fraction as a fertilizer for plant growth in different species and antifouling agents, applicable in aquaculture.
Conventional extraction techniques require high consumption of available resources and thus are ineffective and expensive, especially at an industrial scale. The aim of the study was to optimize the ...ultrasound-assisted extraction of polyphenols from fresh wheatgrass (
Triticum aestivum
L.). The effects of different extraction techniques and solvents were investigated on the yield of extractive substances and antioxidant activity. The ultrasound-assisted extraction technique and ethanol gave the highest yield of extractive substances so that they were used in the optimization studies. The central composite design was employed to find the optimal levels of ethanol concentration, extraction temperature, and extraction time. The total phenolic content was varied in the range of 10.50–15.50 grams of gallic acid equivalents per 100 g of dry weight of plant material (g GAE 100 g
−1
dw). The optimal conditions for ultrasound-assisted extraction were: (1) 56% (v/v) ethanol, (2) temperature of 59 °C, and (3) extraction time of 28 min. The results of ANOVA indicated that the highest impact had the extraction temperature on the total phenolic content. The toxic solvents were not used in the developed extraction procedure. The consumption of energy and raw plant material is estimated to be lower by at least 10% compared to conventional techniques.
Abstract
Background
We evaluated Nix-TB trial data (NCT02333799, N = 109) to provide dosing recommendations to potentially minimize linezolid toxicity in patients with extensively drug-resistant ...tuberculosis. .
Methods
A pharmacokinetic model and toxicodynamic models for peripheral neuropathy, hemoglobin, and platelets were developed. Simulations compared safety outcomes for daily linezolid of 1200 and 600 mg, with and without dose adjustments for toxicity. Severe neuropathy was based on symptom scores from the Brief Peripheral Neuropathy Screen. Severe anemia and thrombocytopenia were defined as ≥ grade 3 adverse events according to the NIAID Division of Microbiology and Infectious Disease Adult Toxicity table.
Results
Predicted concentration-time profiles were a major predictor in all toxicodynamic models. Simulations showed higher percentages of patients with severe neuropathy (median, 19%; 90% confidence interval CI, 17%–22% vs 5%, 4%–7%) and severe anemia (15%, 12%–17% vs 1%, 0%–2%) between 1200 and 600 mg daily linezolid. No differences in severe thrombocytopenia were observed (median, <1% for both daily doses). Generally, neuropathy occurred after 3 to 6 months of treatment and, with protocol-specified management, reversed within 15 months after onset. Simulations indicated that a >10% decrease in hemoglobin level after 4 weeks of treatment would have maximum sensitivity (82%) and specificity (84%) for predicting severe anemia. Reducing the dose from 1200 to 600 mg triggered by this marker may prevent 60% (90% CI, 45%–72%) of severe anemia.
Conclusions
Simple neuropathy symptom and hemoglobin monitoring may guide linezolid dosing to avoid toxicities, but prospective testing is needed to confirm the benefit-to-risk ratio.
Limited information is available about optimal linezolid dosing strategies in patients with tuberculosis. We analyzed data from Nix-TB to describe the relationship between linezolid exposure and major toxicities. We provide practical recommendations about linezolid dosing to minimize severe adverse events.
We report the results of a study comparing the temporal dynamics of thematic and taxonomic knowledge activation in a picture-word priming paradigm using event-related potentials. Although we found no ...behavioral differences between thematic and taxonomic processing, ERP data revealed distinct patterns of N400 and P600 amplitude modulation for thematic and taxonomic priming. Thematically related target stimuli elicited less negativity than taxonomic targets between 280-460 ms after stimulus onset, suggesting easier semantic processing of thematic than taxonomic relationships. Moreover, P600 mean amplitude was significantly increased for taxonomic targets between 520-600 ms, consistent with a greater need for stimulus reevaluation in that condition. These results offer novel evidence in favor of a dissociation between thematic and taxonomic thinking in the early phases of conceptual evaluation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Empirical Bayes (“post hoc”) estimates (EBEs) of
ηs
provide modelers with diagnostics: the EBEs themselves, individual prediction (IPRED), and residual errors (individual weighted residual (IWRES)). ...When data are uninformative at the individual level, the EBE distribution will shrink towards zero (
η
-shrinkage, quantified as 1-SD(
η
EBE
)/
ω
), IPREDs towards the corresponding observations, and IWRES towards zero (
ε
-shrinkage, quantified as 1-SD(IWRES)). These diagnostics are widely used in pharmacokinetic (PK) pharmacodynamic (PD) modeling; we investigate here their usefulness in the presence of shrinkage. Datasets were simulated from a range of PK PD models, EBEs estimated in non-linear mixed effects modeling based on the true or a misspecified model, and desired diagnostics evaluated both qualitatively and quantitatively. Identified consequences of
η-
shrinkage on EBE-based model diagnostics include non-normal and/or asymmetric distribution of EBEs with their mean values (“ETABAR”) significantly different from zero, even for a correctly specified model; EBE–EBE correlations and covariate relationships may be masked, falsely induced, or the shape of the true relationship distorted. Consequences of
ε
-shrinkage included low power of IPRED and IWRES to diagnose structural and residual error model misspecification, respectively. EBE-based diagnostics should be interpreted with caution whenever substantial
η-
or
ε
-shrinkage exists (usually greater than 20% to 30%). Reporting the magnitude of
η
- and
ε-
shrinkage will facilitate the informed use and interpretation of EBE-based diagnostics.
The sites of mycobacterial infection in the lungs of tuberculosis (TB) patients have complex structures and poor vascularization, which obstructs drug distribution to these hard-to-reach and ...hard-to-treat disease sites, further leading to suboptimal drug concentrations, resulting in compromised TB treatment response and resistance development. Quantifying lesion-specific drug uptake and pharmacokinetics (PKs) in TB patients is necessary to optimize treatment regimens at all infection sites, to identify patients at risk, to improve existing regimens, and to advance development of novel regimens. Using drug-level data in plasma and from 9 distinct pulmonary lesion types (vascular, avascular, and mixed) obtained from 15 hard-to-treat TB patients who failed TB treatments and therefore underwent lung resection surgery, we quantified the distribution and the penetration of 7 major TB drugs at these sites, and we provide novel tools for treatment optimization.
A total of 329 plasma- and 1,362 tissue-specific drug concentrations from 9 distinct lung lesion types were obtained according to optimal PK sampling schema from 15 patients (10 men, 5 women, aged 23 to 58) undergoing lung resection surgery (clinical study NCT00816426 performed in South Korea between 9 June 2010 and 24 June 2014). Seven major TB drugs (rifampin RIF, isoniazid INH, linezolid LZD, moxifloxacin MFX, clofazimine CFZ, pyrazinamide PZA, and kanamycin KAN) were quantified. We developed and evaluated a site-of-action mechanistic PK model using nonlinear mixed effects methodology. We quantified population- and patient-specific lesion/plasma ratios (RPLs), dynamics, and variability of drug uptake into each lesion for each drug. CFZ and MFX had higher drug exposures in lesions compared to plasma (median RPL 2.37, range across lesions 1.26-22.03); RIF, PZA, and LZD showed moderate yet suboptimal lesion penetration (median RPL 0.61, range 0.21-2.4), while INH and KAN showed poor tissue penetration (median RPL 0.4, range 0.03-0.73). Stochastic PK/pharmacodynamic (PD) simulations were carried out to evaluate current regimen combinations and dosing guidelines in distinct patient strata. Patients receiving standard doses of RIF and INH, who are of the lower range of exposure distribution, spent substantial periods (>12 h/d) below effective concentrations in hard-to-treat lesions, such as caseous lesions and cavities. Standard doses of INH (300 mg) and KAN (1,000 mg) did not reach therapeutic thresholds in most lesions for a majority of the population. Drugs and doses that did reach target exposure in most subjects include 400 mg MFX and 100 mg CFZ. Patients with cavitary lesions, irrespective of drug choice, have an increased likelihood of subtherapeutic concentrations, leading to a higher risk of resistance acquisition while on treatment. A limitation of this study was the small sample size of 15 patients, performed in a unique study population of TB patients who failed treatment and underwent lung resection surgery. These results still need further exploration and validation in larger and more diverse cohorts.
Our results suggest that the ability to reach and maintain therapeutic concentrations is both lesion and drug specific, indicating that stratifying patients based on disease extent, lesion types, and individual drug-susceptibility profiles may eventually be useful for guiding the selection of patient-tailored drug regimens and may lead to improved TB treatment outcomes. We provide a web-based tool to further explore this model and results at http://saviclab.org/tb-lesion/.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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