Use of Residual Malt from an Artisanal Beer Brewing Process in the Biosynthesis of Silver Nanoparticles Mediated by Nucleating and Structure-Directing Agents.

Biosynthesized silver nanoparticles (AgNPs) are widely used in varied applications, which are morphology dependent. Consequently, a morphology-controlled synthesis is mandatory. Although there are several studies focused on the plant extract-based biosynthesis of metallic nanoparticles, the use of extracts obtained from agro-wastes is scant. Furthermore, information regarding morphology modification through the use of additional agents is even more scarce. Thus, in this study, AgNPs were synthesized using a malt extract (ME) obtained from an artisanal beer brewing process residue. Additionally, sodium chloride (NaCl), gum arabic (GA), and talc (T) were used in an attempt to modify the morphology of AgNPs. XRD, DLS, SEM, and TEM results demonstrate that stable AgNPs of different sizes and shapes were synthesized. FTIR, HPLC analysis, and the quantification of total proteins, free amino acids, reducing sugars, and total polyphenols before and after AgNPs synthesis showed that ME biomolecules allowed them to act as a source of reducing and stabilizing agents. Therefore, this study provides evidence that ME can be successfully used to biosynthesize AgNPs. Additionally, the antibacterial activity of AgNPs against Gram-negative and Gram-positive bacteria was evaluated. Results indicate that AgNPs show a higher antibacterial activity against Gram-positive bacteria.

HPLC-UV evaluation of a microwave assisted method as an active drug loading technique for exosome-based drug delivery system.

This paper evaluates the potential of a microwave radiation (MR) assisted method as an active drug loading technique for exosomes using polyphenolic nutraceuticals as model drugs (i.e. resveratrol (RV), rosmarinic acid (RA), pterostilbene (PT) and epigallocatechin gallate (EG)). MR is evaluated as a single step method and as part of a two-step method consisting of incubation (IN) followed by MR. The effect of exposure time, loading method and type of nutraceutical on the loading efficiency were investigated using high performance liquid chromatography (HPLC), X-ray diffraction (XRD) and flow cytometry. Additionally, dynamic light scattering (DLS) was used to determine the size of exosomes. Loading efficiency results indicated that MR is a promising method to be used as loading process. Results also suggested that due to different levels of hydrophobicity, related to the number of OH groups, the absorption of polyphenols into the bilayer of EVs is different for each molecule. According to XRD results, MR could not be used with any cargo drug since radiation could affect the chemical composition and the degree of crystallinity of such molecules, consequently affecting their performance. Flow cytometry results indicated that loading methods negatively affect exosome concentration.

A Novel Approach to Obtain Vaccine Effectiveness Continuous Profiles. Example Case: COVID-19 in Elderly Mexicans.

Population-wide vaccination is the most promising long-term COVID-19 disease management strategy. However, the protection offered by the currently available COVID-19 vaccines wanes over time, requiring boosters to be periodically given, which represents an unattainable challenge, especially if it is necessary to apply several doses per year. Therefore, it is essential to design strategies that contribute to maximizing the control of the pandemic with the available vaccines. Achieving this objective requires knowing, as precisely and accurately as possible, the changes in vaccine effectiveness over time in each population group, considering the eventual dependence on age, sex, etc. Thus, the present work proposes a novel approach to calculating realistic effectiveness profiles against symptomatic disease. In addition, this strategy can be adapted to estimate realistic effectiveness profiles against hospitalizations or deaths. All such time-dependent profiles allow the design of improved vaccination schedules, where each dose can be administrated to the population groups so that the fulfillment of the containment objectives is maximized. As a practical example for this analysis, vaccination against COVID-19 in Mexico was considered. However, this methodology can be applied to other countries' data or to characterize future vaccines with time-dependent effectiveness values. Since this strategy uses aggregated observational data collected from massive databases, assumptions about the data validity and the course of the studied epidemic could eventually be necessary.

Lamotrigine Extraction and Quantification by UPLC-DAD in Plasma from Patients with Bipolar Disorder.

A sensitive and efficient analytical process for detecting lamotrigine in acidic solution based in ultra-high-performance liquid chromatography-diode array detector (UPLC-DAD) was developed; the stationary phase used was a C8, 150 × 4.6 mm, 2.6 µm. The mobile phase consisted of acetonitrile/acidified water (0.01% H3PO4 and 0.005% triethylamine, pH 2.4) (25 : 75 v/v). Limits of detection and quantification were 0.02 µg/mL and 0.05 µg/mL, respectively. The working interval for the evaluation of the method ranged from 0.05 to 12 µg/mL, and the linear fit of the experimental data has a value of r2≥0.98. Before quantifying lamotrigine in plasma of patients with bipolar disorder, lamotrigine was released from plasma proteins with a 0.2 M sodium hydroxide solution, and then proteins were removed by precipitation with acetonitrile. Afterward, the lamotrigine base was dissolved in ethyl acetate. This extract was reconstituted in potassium phosphate solution (pH 2.4) to obtain more than 98% of lamotrigine protonated in N2, which was detected and quantified as indicated above. The absolute percentage of lamotrigine recovery is ≥80% for all tested concentration levels. The accuracy and precision of the method have %CV values <4% for the lamotrigine levels of 3, 6, and 9 µg/mL. The correlation coefficient for the used concentration range is 0.99. The analytical method is precise and sensitive to measure lamotrigine levels expected in plasma of BD patients and these levels were in the therapeutic dose range.

A Methodology Towards Mechanical Properties Optimization of Three-Component Polymers by the Gradual Variation of Feed Composition in Semi-Continuous Emulsion-Free Radical Polymerization.

In this work, a new methodology for the synthesis of three-component polymers (TCPs) was developed using a seeded, semi-continuous free-radical emulsion polymerization towards the optimization of the moduli-ultimate deformation performance and energy dissipation capacity for a styrene (S), n-butyl acrylate (BA), and 4-vinylbenzyl chloride (VBC) system. The three components were sequentially fed in pairs, varying feed composition along the conversion using S as the common monomer. To prepare a reference material, an industrial method was utilized with those monomers, using an equivalent global composition in a two-stage batch process (TS). Nanophase formation in the particles was observed by transmission electron microscopy (TEM), while the separation of the phases in the solid samples was observed by atomic force microscopy (AFM). The changes in glass transition temperature were determined by differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA). The latter was primarily used to compare mechanodynamic properties as a function of temperature for the two synthesis methods used. Thus, the higher toughness of the forced composition three-component polymeric materials was evaluated by means of their energy dissipation capacity, toughness, and stress-strain measurements at several temperatures.

Artemisia dracunculus Extracts Obtained by Organic Solvents and Supercritical CO2 Produce Cytotoxic and Antitumor Effects in Mice with L5178Y Lymphoma.

We investigated the cytotoxic and antitumor effects of nine leaf extracts from Artemisia dracunculus (Tarragon). Five extracts were obtained using different organic solvents and four by supercritical CO2. The cytotoxic effects were expressed as IC50 in 100, 80, 80, 100, and 80 µg/mL by respective solvents: hexane, ethyl acetate, acetone, ethanol, and acetonitrile in L5178Y lymphoma cells. For supercritical CO2 extract A, IC50 was 100 µg/mL; for extracts C and D, IC50 was 150 µg/mL. The antitumor activity was assessed through a tumor growth inhibition test that measured ascites fluid volume and tumor cell counts of BALB/c mice (2 × 104 cells L5178Y i.p.). Twenty-four hours after inoculation, mice were treated with 100 mg/kg of acetonitrile extract or extract SF-A daily for 15 days in independent groups of five mice, using two administration routes. We observed tumor evolution with and without treatment. Without treatment, tumor evolution was 17,969 × 106 ± 5485 L5178Y cells in 2.6 mL ascites volume, whereas the orally treated acetonitrile extract group showed 0.1 × 106 ± 0.07 L5178Y cells (P < .05). The oral SF-A group showed 12.9 × 106 ± 243 L5178Y cells, and intraperitoneal (i.p.)-treated SF-A group showed 0.1 × 106 ± 0.05 L5178Y cells (P < .05) without any ascites volume development. The acetonitrile extract contains abundant polyphenols and possibly a flavone with antioxidant activity. The SF-A contains abundant alkamides. Both extracts are complexes and the identity of the compounds responsible for observed antitumor activity remains unknown.

Calculating the metabolizable energy of macronutrients: a critical review of Atwater's results.

The current values for metabolizable energy of macronutrients were proposed in 1910. Since then, however, efforts to revise these values have been practically absent, creating a crucial need to carry out a critical analysis of the experimental methodology and results that form the basis of these values. Presented here is an exhaustive analysis of Atwater's work on this topic, showing evidence of considerable weaknesses that compromise the validity of his results. These weaknesses include the following: (1) the doubtful representativeness of Atwater's subjects, their activity patterns, and their diets; (2) the extremely short duration of the experiments; (3) the uncertainty about which fecal and urinary excretions contain the residues of each ingested food; (4) the uncertainty about whether or not the required nitrogen balance in individuals was reached during experiments; (5) the numerous experiments carried out without valid preliminary experiments; (6) the imprecision affecting Atwater's experimental measurements; and (7) the numerous assumptions and approximations, along with the lack of information, characterizing Atwater's studies. This review presents specific guidelines for establishing new experimental procedures to estimate more precise and/or more accurate values for the metabolizable energy of macronutrients. The importance of estimating these values in light of their possible dependence on certain nutritional parameters and/or physical activity patterns of individuals is emphasized. The use of more precise values would allow better management of the current overweight and obesity epidemic.

Effect of Artemisia dracunculus Administration on Glycemic Control, Insulin Sensitivity, and Insulin Secretion in Patients with Impaired Glucose Tolerance.

To evaluate the effect of Artemisia dracunculus on glycemic control, insulin sensitivity, and insulin secretion in patients with impaired glucose tolerance (IGT). A randomized, double blind, placebo-controlled clinical trial was performed in 24 patients with diagnosis of IGT. Before and after the intervention, glucose and insulin levels were measured every 30 min for 2 h after a 75-g dextrose load, along with glycated hemoglobin A1c (A1C) and lipid profile. Twelve patients received A. dracunculus (1000 mg) before breakfast and dinner for 90 days; the remaining 12 patients received placebo. Area under the curve (AUC) of glucose and insulin, total insulin secretion, first phase of insulin secretion, and insulin sensitivity were calculated. Wilcoxon signed-rank, Mann-Whitney U, and chi-square tests were used for statistical analyses. The institutional ethics committee approved the protocol. After A. dracunculus administration, there were significant decreases in systolic blood pressure (SBP; 120.0 ± 11.3 vs. 113.0 ± 11.2 mmHg, P < .05), A1C (5.8 ± 0.3 vs. 5.6% ± 0.4%, P < .05), AUC of insulin (56,136.0 ± 27,426.0 vs. 44,472.0 ± 23,370.0 pmol/L, P < .05), and total insulin secretion (0.45 ± 0.23 vs. 0.35 ± 0.18, P < .05), with a significant increase in high-density lipoprotein cholesterol (HDL-C) (1.3 ± 0.3 vs. 1.4 ± 0.3 mmol/L, P < .05). There were no significant differences after placebo administration. A. dracunculus administration for 90 days in patients with IGT significantly decreased SBP, A1C, AUC of insulin, and total insulin secretion with a significant increase in HDL-C levels.

Mitochondrial ATPase activity and membrane fluidity changes in rat liver in response to intoxication with buckthorn (Karwinskia humboldtiana).

BACKGROUND: Karwinskia humboldtiana (Kh) is a poisonous plant of the rhamnacea family. To elucidate some of the subcellular effects of Kh toxicity, membrane fluidity and ATPase activities as hydrolytic and as proton-pumping activity were assessed in rat liver submitochondrial particles. Rats were randomly assigned into control non-treated group and groups that received 1, 1.5 and 2 g/Kg body weight of dry powder of Kh fruit, respectively. Rats were euthanized at day 1 and 7 after treatment. RESULTS: Rats under Kh treatment at all dose levels tested, does not developed any neurologic symptoms. However, we detected alterations in membrane fluidity and ATPase activity. Lower dose of Kh on day 1 after treatment induced higher mitochondrial membrane fluidity than control group. This change was strongly correlated with increased ATPase activity and pH gradient driven by ATP hydrolysis. On the other hand, membrane fluidity was hardly affected on day 7 after treatment with Kh. Surprisingly, the pH gradient driven by ATPase activity was significantly higher than controls despite an diminution of the hydrolytic activity of ATPase. CONCLUSIONS: The changes in ATPase activity and pH gradient driven by ATPase activity suggest an adaptive condition whereby the fluidity of the membrane is altered.

Mitochondrial ATPase activity and membrane fluidity changes in rat liver in response to intoxication with Buckthorn (Karwinskia humboldtiana)

BACKGROUND: Karwinskia humboldtiana (Kh) is a poisonous plant of the rhamnacea family. To elucidate some of the subcellular effects of Kh toxicity, membrane fluidity and ATPase activities as hydrolytic and as proton-pumping activity were assessed in rat liver submitochondrial particles. Rats were randomly assigned into control non-treated group and groups that received 1,1.5 and 2 g/Kg body weight of dry powder of Kh fruit, respectively. Rats were euthanized at day 1 and 7 after treatment. RESULTS: Rats under Kh treatment at all dose levels tested, does not developed any neurologic symptoms. However, we detected alterations in membrane fluidity and ATPase activity. Lower dose of Kh on day 1 after treatment induced higher mitochondrial membrane fluidity than control group. This change was strongly correlated with increased ATPase activity and pH gradient driven by ATP hydrolysis. On the other hand, membrane fluidity was hardly affected on day 7 after treatment with Kh. Surprisingly, the pH gradient driven by ATPase activity was significantly higher than controls despite an diminution of the hydrolytic activity of ATPase. CONCLUSIONS: The changes in ATPase activity and pH gradient driven by ATPase activity suggest an adaptive condition whereby the fluidity of the membrane is altered.

Effect of vildagliptin on glucose and insulin concentrations during a 24-hour period in type 2 diabetes patients with different ranges of baseline hemoglobin A1c levels.

BACKGROUND: Currently, it is still unknown whether differences in glycemic control have any effect on glucose and insulin kinetics after vildagliptin administration. The aim of this study was to evaluate the effect of vildagliptin on glucose and insulin concentrations during a 24-h period in type 2 diabetes patients with different ranges of baseline hemoglobin A1c (A1C) levels. PATIENTS AND METHODS: A randomized, double-blind, crossover, placebo-controlled clinical trial was carried out in 12 drug-naive adult volunteers with type 2 diabetes and overweight or obesity. Subjects had fasting glucose values between 7.2 and 13.3 mmol/L. Six patients had A1C between 7.0% and 8.4% (Group A), and the remaining subjects had A1C between 8.5% and 10.0% (Group B). Patients received oral administration of vildagliptin (50 mg twice daily) or placebo in a crossover manner for two consecutive days. Until the second day of the interventions, glucose and insulin concentrations were measured every hour during a 24-h period, and areas under the curve (AUCs) were calculated. Statistical analyses were evaluated with Wilcoxon and Mann-Whitney U tests. RESULTS: There were significant decreases in glucose concentrations after vildagliptin administration in both groups when comparing placebo in all measurements throughout the 24-h period and in the AUC. There were no significant changes in insulin concentration in both groups after vildagliptin administration when comparing placebo in all measurements throughout the 24-h period and in the AUC. CONCLUSIONS: Vildagliptin administration improved glucose control during a 24-h period in type 2 diabetes patients, independent of the basal A1C level, without changes in insulin levels.

Improved methodology to measure surface tension and its application to polystyrene or poly(methyl methacrylate) in styrene solutions.

Several methods to measure surface tension involve some inconveniences when applied to moderate or highly viscous polymer solutions. Therefore, an improved version of the weight drop method (WDM) is proposed here. In addition, a comparative analysis of methods is carried out, including the drop profile (DPM), the selected planes (SPM), the WDM and the one proposed here (WDSM), finding that the WDSM is as easy to apply as the SPM and the WDM, although in practical conditions it is much more accurate than either of them. Moreover, the WDSM allows to reproduce the results that can be obtained using DPM, but, in general, it is much easier to implement and apply than such method. The WDSM was used to determine surface tension in polystyrene or poly(methyl methacrylate) in styrene solutions, where the dependence of such property with polymer average molecular weight and polymer concentration was experimentally evaluated.