Istodobno spektrofotometrijsko određivanje losartan kalija, amlodipin besilata i hidroklorotiazida u farmaceutskim pripravcima kemometrijskom metodom

In the present work, four different spectrophotometric methods for simultaneous estimation of losartan potassium, amlodipine besilate and hydrochlorothiazide in raw materials and in formulations are described. Overlapped data was quantitatively resolved by using chemometric methods, classical least squares (CLS), multiple linear regression (MLR), principal component regression (PCR) and partial least squares (PLS). Calibrations were constructed using the absorption data matrix corresponding to the concentration data matrix, with measurements in the range of 230.5350.4 nm (∆λ = 0.1 nm) in their zero order spectra. The linearity range was found to be 840, 15 and 315 μg ml1 for losartan potassium, amlodipine besilate and hydrochlorothiazide, respectively. The validity of the proposed methods was successfully assessed for analyses of drugs in the various prepared physical mixtures and in tablet formulations.U radu su opisane četiri spektrofotometrijske metode za istodobno određivanje losartan kalija, amlodipin besilata i hidroklorotiazida u sirovinama i farmaceutskim pripravcima. Podaci koji su se preklapali kvantitativno su razlučeni kemometrijskim metodama, klasičnom metodom najmanjih kvadrata (CLS), multiplom linearnom regresijom (MLR), regresijom glavnih komponenata (PCR) te metodom parcijalnih najmanjih kvadrata (PLS). Kalibracije su provedene koristeći podatke o ovisnosti apsorpcije o koncentracijama, mjereći spektre nultog reda u rasponu 230,5350,4 nm (∆λ = 0,1 nm). Linearnost za losartan kalij bila je 840, za amlodipin besilat 15, a za hidroklorotiazid 315 μg ml1. Valjanost predloženih metoda uspješno je potvrđena analizom navedenih lijekova u različitim pripremljenim smjesama i tabletama

Aptamer-based field-effect biosensor for tenofovir detection

During medical treatment it is critical to maintain the circulatory concentration of drugs within their therapeutic range. A novel biosensor is presented in this work to address the lack of a reliable point-of-care drug monitoring system in the market. The biosensor incorporates high selectivity and sensitivity by integrating aptamers as the recognition element and field-effect transistors as the signal transducer. The drug tenofovir was used as a model small molecule. The biointerface of the sensor is a binary self-assembled monolayer of specific thiolated aptamer and 6-mercapto-1-hexanol (MCH), whose ratio was optimized by electrochemical impedance spectroscopy measurements to enhance the sensitivity towards the specific target. Surface plasmon resonance, performed under different buffer conditions, shows optimum specific and little non-specific binding in phosphate buffered saline. The dose-response behavior of the field-effect biosensor presents a linear range between 1 nM and 100 nM of tenofovir and a limit of detection of 1.2 nM. Two non-specific drugs and one non-specific aptamer, tested as stringent control candidates, caused negligible responses. The applications were successfully extended to the detection of the drug in human serum. As demonstrated by impedance measurements, the aptamer-based sensors can be used for real-time drug monitoring

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Incorporation of Defatted Apple Seeds in Chewing Gum System and Phloridzin Dissolution Kinetics

Apple seeds are among the major natural sources of antioxidants and can be used in various industries. In this regard, antioxidant activity, total phenolic content, and individual phenolic compounds analyzes of defatted apple seed flours were firstly done in our study. According to these analyzes, total phenolic content, DPPH and ABTS radical scavenging activity of defatted seed flours were determined between 2861 and 5141 mg GAE/kg defatted seed, 21.45–43.56 μmol, and 291.50–391.79 μmol Trolox/g defatted seed, respectively. It was observed that the content of phloridzin represented 52–67% and 75–83% of the total phenolics that measured by the Folin-Ciocalteu assay and HPLC method, respectively. In the second part, chewing gums including defatted seeds were prepared and characterized in terms of phloridzin dissolution. The novel model described dissolution kinetics of phloridzin from chewing gum better than Higuchi and Korsmeyer-Peppas models. The results de- monstrated that 5 min was enough for the dissolution of almost all phloridzin (88.43–96%) determined by centrifugation method and according to the model parameters, the chewing gum formulation can be optimized for providing controlled dissolution. In conclusion, chewing gum could be a suitable delivering material for phloridzin uptake, and apple seeds, a valuable agricultural by-product, could be evaluated in this way

A modeling approach in the interpretation of starch pasting properties

In this work, starch pasting curves were reinterpreted with suitable models to show deficiency of widely used starch pasting parameters in the literature. The aim was to attract scientific attentions to the behavior and dynamics of the curve with respect to process parameters instead of values on the curve. Mainly, pasting curve was separated into four parts combining sigmoidal gelatinization model, exponential thinning model and Arrhenius temperature model. For the gelatinization part, starch swelling rate, water binding capacity and starch resistivities to heat and shear might be compared by the proposed model parameters. Amylose and damaged starch contents of starches had a good relation with Arrhenius and exponential model parameters. Activation energy values gave clues about retrogradation rate of starches and changed between 7142 and 17,327 kJ/mol. © 2017 Elsevier Lt

Dispersion stability and thermal conductivity of propylene glycol based nanofluids

The dispersion stability and thermal conductivity of propylene glycol-based nanofluids containing Al2O3 and TiO2 nanoparticles were studied in the temperature range of 20–80 °C. Nanofluids with different concentrations of nanoparticles were formulated by the two-step method and no dispersant was used. In contrast to the common belief, the average particle size of nanofluids was observed to decrease with increasing temperature, and nanofluids showed an excellent stability over the temperature range of interest. Thermal conductivity enhancement for both studied nanofluids was a nonlinear function of concentration and was temperature independent. Theoretical analyses were also performed using existing models compared with experimental results. The model based on the aggregation theory appears to be the best

Development and validation of a stability-indicating RP-LC method for the determination of anticancer drug epirubicin in pharmaceuticals

In the present paper, sensitive, rapid, and different analytical methodology was developed for the determination of anticancer drug epirubicin (EPR). The mixture of epirubicin and moxifloxacin as internal standard was separated on a reversed phase Waters Spherisorb ODS1 column (250mm × 4.6mm × 5mm) using acetonitrile/water (30:70 v/v) mixture containing 15 mM phosphoric acid as mobile phase at 0.6 mL min-1 flow rate and 30 C. Also degradation studies were conducted as stress conditions of UV light, acidic hydrolysis, alkaline hydrolysis, oxidation, and heat in oven (100°C), to evaluate the ability of the proposed method for the separation of EPR from its degradation products. The validated method suggests routine analysis of EPR in differently equipped laboratories. © 2014 Copyright Taylor & Francis Group, LLC

Alternative Tempering of Sugar-Free Dark Chocolates By βv Seeding: Sensorial, Micro-structural, and Some Physical Properties and Volatile Profile

In this study, sugar-free dark chocolate was produced from isomalt and maltitol by βV seeding technique as an alternative to conventional tempering process. The effect of βV seed concentrations on the particle size dis- tribution, textural, rheological and melting properties of the end products was studied, and the results were compared with those of conventional sugar-free dark chocolates. For this aim, conched dark chocolates were melted and crystallized with βV seeds added at different concentrations (0.5, 0.6, 0.7, 0.8, 0.9 and 1.0 %, m/m). Conventional tempering process was performed by using temper machine (47–27–32 °C). Brightness, chroma, whiteness index and tetramethyl pyrazine content (as marker compounds of dark chocolate volatile compound) were not influenced by seeding technique compared to conventional tempering method. The water activity of the dark chocolate samples was substantially affected by βV seed level according to used bulk sweetener. How- ever, all the values were determined below 0.4 which is critical limit for chocolate. Regarding overall acceptabil- ity, sugar-free dark chocolates tempered by βv seeds had very close scores compared with conventional one, implying that sugar-free chocolates can be produced by βv crystals with desired quality characteristics similar to conventional samples. Results of this study showed that it is possible to produce sucrose-free dark chocolates by using βV seeds with desired quality similar to chocolate produced by using conventional tempering