Comparison of dynamic susceptibility contrast (DSC) using gadolinium and iron-based contrast agents in high-grade glioma at high-field MRI.

PURPOSE: To compare DSC-MRI using Gadolinium (GBCA) and Ferumoxytol (FBCA) in high-grade glioma at 3T and 7T MRI field strengths. We hypothesized that using FBCA at 7T would enhance the performance of DSC, as measured by contrast-to-noise ratio (CNR). METHODS: Ten patients (13 lesions) were assigned to 3T (6 patients, 6 lesions) or 7T (4 patients, 7 lesions). All lesions received 0.1 mmol/kg of GBCA on day 1. Ten lesions (4 at 3T and 6 at 7T) received a lower dose (0.6 mg/kg) of FBCA, followed by a higher dose (1.0-1.2 mg/kg), while 3 lesions (2 at 3T and 1 at 7T) received only a higher dose on Day 2. CBV maps with leakage correction for GBCA but not for FBCA were generated. The CNR and normalized CBV (nCBV) were analyzed on enhancing and non-enhancing high T2W lesions. RESULTS: Regardless of FBCA dose, GBCA showed higher CNR than FBCA at 7T, which was significant for high-dose FBCA (p < .05). Comparable CNR between GBCA and high-dose FBCA was observed at 3T. There was a trend toward higher CNR for FBCA at 3T than 7T. GBCA also showed nCBV twice that of FBCA at both MRI field strengths with significance at 7T. CONCLUSION: GBCA demonstrated higher image conspicuity, as measured by CNR, than FBCA on 7T. The stronger T2* weighting realized with higher magnetic field strength, combined with FBCA, likely results in more signal loss rather than enhanced performance on DSC. However, at clinical 3T, both GBCA and FBCA, particularly a dosage of 1.0-1.2 mg/kg (optimal for perfusion imaging), yielded comparable CNR.

Thermophysical properties of blends composed of Amazonian fats and soybean oil.

Thermophysical properties of blends composed of soybean oil and fats obtained from fruits and seeds from Brazilian Amazonian region (Murumuru, Tucuma, and Bacuri) were investigated, looking for more sustainable alternatives to the mostly used industrial fats, for applications in product formulation. Fatty acid (FA) and triacylglycerol composition, nutritional indexes, solid fat content (SFC), compatibility, consistency, melting, and crystallization profiles were determined. Soybean oil increased blends' unsaturated FA profile, leading to lower SFC, but higher nutritional quality. Fats' melting profiles were significantly altered with soybean oil addition: temperatures decreased with the increase in oil content. Iso-solids diagrams showed that lipids were compatible, which is a technological advantage. SFC and consistency profiles suggested that tucuma and murumuru fats could be used as hardstocks for lipid products, and bacuri fat could be applied in products such as margarine and spreads. Blends could improve fats' spreadability and other technological properties, which is promising for applications in products formulation.

Thermodynamic and structural properties of lipid-photosensitizer conjugates mixed with phospholipids: Impact on the formation and stability of nano-assemblies.

The photosensitizer Phenalenone (PN) was grafted with one or two lipid (C18) chains to form pure nano-assemblies or mixed lipid vesicles suitable for photodynamic therapy. Mixtures of PN-C18 conjugates with stearoyl-oleoyl phosphatidylcholine (SOPC) form vesicles that disintegrate into bilayer sheets as the concentration of PN-C18 conjugates increases. We hypothesized that PN-C18 conjugates control the thermodynamic and structural properties of the mixtures and induce the disintegration of vesicles due to PN π-π-interactions. Monolayers were analyzed by surface pressure and grazing incidence X-ray diffraction (GIXD) measurements, and vesicles by differential scanning calorimetry and cryo-TEM. The results showed that PN-triazole-C18 (1A) and PN-NH-C18 (1B) segregate from the phospholipid domains. PN-(C18)2 (conjugate 2) develops favorable interactions with SOPC and distearoyl-phosphatidylcholine (DSPC). GIXD demonstrates the contribution of SOPC to the structuring of conjugate 2 and the role of the major component in controlling the structural properties of DSPC-conjugate 2 mixtures. Above 10 mol% conjugate 2 in SOPC vesicles, the coexistence of domains with different molecule packing leads to conjugate segregation, vesicle deformation, and the formation of small bilayer discs stabilized by the inter-bilayer π-π stacking of PN molecules.

Comparing Different Chemometric Approaches to Detect Adulteration of Cold-Pressed Flaxseed Oil with Refined Rapeseed Oil Using Differential Scanning Calorimetry.

Flaxseed oil is one of the best sources of n-3 fatty acids, thus its adulteration with refined oils can lead to a reduction in its nutritional value and overall quality. The purpose of this study was to compare different chemometric models to detect adulteration of flaxseed oil with refined rapeseed oil (RP) using differential scanning calorimetry (DSC). Based on the melting phase transition curve, parameters such as peak temperature (T), peak height (h), and percentage of area (P) were determined for pure and adulterated flaxseed oils with an RP concentration of 5, 10, 20, 30, and 50% (w/w). Significant linear correlations (p ≤ 0.05) between the RP concentration and all DSC parameters were observed, except for parameter h1 for the first peak. In order to assess the usefulness of the DSC technique for detecting adulterations, three chemometric approaches were compared: (1) classification models (linear discriminant analysis-LDA, adaptive regression splines-MARS, support vector machine-SVM, and artificial neural networks-ANNs); (2) regression models (multiple linear regression-MLR, MARS, SVM, ANNs, and PLS); and (3) a combined model of orthogonal partial least squares discriminant analysis (OPLS-DA). With the LDA model, the highest accuracy of 99.5% in classifying the samples, followed by ANN > SVM > MARS, was achieved. Among the regression models, the ANN model showed the highest correlation between observed and predicted values (R = 0.996), while other models showed goodness of fit as following MARS > SVM > MLR. Comparing OPLS-DA and PLS methods, higher values of R2X(cum) = 0.986 and Q2 = 0.973 were observed with the PLS model than OPLS-DA. This study demonstrates the usefulness of the DSC technique and importance of an appropriate chemometric model for predicting the adulteration of cold-pressed flaxseed oil with refined rapeseed oil.

Effect of ultrasound-assisted osmotic dehydration on the drying kinetics, water state, and physicochemical properties of microwave vacuum-dried potato slices.

The effects of pre-treatments on the drying characteristics, water state, thermal properties, and bulk shrinkage of potato slices during microwave vacuum drying (MVD) were investigated. The pre-treatment included ultrasound in distilled water (USOD-0%), and ultrasound-assisted osmotic dehydration in a 60% sucrose solution (USOD-60%). Results showed that the drying time of potato slices was reduced and the drying rate was increased when USOD-0% was used as a pretreatment, whereas USOD-60% had a negative effect on the drying rate of the samples. The Weibull model was effective in predicting the water changes in potato slices during the drying process. NMR analysis revealed that the relative content of immovable water (M22) increased initially, then decreased for drying, while the transverse relaxation time (T2) and the relative content of free water (M23) decreased consistently. The DSC results indicated that the glass transition temperature (Tg) had an inverse relationship with the water content of the samples, yet had virtually no influence on the volume shrinkage. The sample volumes decreased linearly with the decrease in water content during the initial drying stages. USOD pre-treatment lessened the volume shrinkage of MVD potato slices. Static gravimetry was used to determine the moisture sorption isotherms of MVD potato slices at 30 °C within the aw range of 0.113-0.923. The GAB model accurately fitted the experimental sorption data, which showed sigmoid shape curves for the MVD samples. When aw values exceeded 0.7, the USOD-60% treatment significantly reduce the water sorption capacity of MVD potato slices, while USOD-0% treatment was observed to increase the hygroscopic properties of MVD samples. Compared with the control, USOD-0% pretreatment significantly increased the monolayer water content (X0), sorption surface area (S0), the thickness of sorbed water multilayer (tm), and density of sorbed water (Ds) values of MVD potato slices, while USOD-60% decreased these values.

Physicochemical and functional properties of rainbow trout (Oncorhynchus mykiss) hydrolysate.

Due to the continuous growth of the world population, there is an urgent need to find sustainable sources of high-quality protein. Fish side streams rich in essential nutrients and accounting for 60-70% of the whole fish, represent a sustainable source for recovery of valuable protein compounds. The present study aimed at extensive characterization of physicochemical, antioxidant and techno-functional properties of fish protein hydrolysate (FPH) obtained from farmed rainbow trout (Oncorhynchus mykiss). The FPH was produced from a minced rainbow trout raw material by enzymatic hydrolysis performed at 50 °C with addition of 0.05% w/w papain and 0.05% w/w bromelain. After inactivation of the proteases at 90 °C for 10 min, the content of the bioreactor was centrifuged, and the soluble protein fraction (FPH) was collected and freeze-dried. The total protein content of the FPH with 17.24% degree of hydrolysis was high (88.9%) and mainly represented by water-soluble proteins, while the lipid content was below 1%. In addition to the high protein content, trout hydrolysate had low protein oxidation values characterized by a relatively low total carbonyl content together with high amount of thiol groups (3.64 ± 0.31 and 20.7 ± 0.6 nmol/mg protein, respectively). No glass transition was detected in the differential scanning calorimetry (DSC) heat flow curves, suggesting lack of unfreezable solution formation in the FPH at freezing temperatures. The viscosity of FPH showed typical Newtonian behaviour. A peptidomic investigation (using HPLC-MS/MS technique) displayed chemical composition of the trout hydrolysate and identified peptide sequences which are present in the hydrolysate mixture, as well as proteins to which each peptide belongs to. In conclusion, it was suggested to use the obtained trout hydrolysate as a functional ingredient in the food and nutraceutical industry.

Interaction of guanidinium and ammonium cations with phosphatidylcholine and phosphatidylserine lipid bilayers - Calorimetric, spectroscopic and molecular dynamics simulations study.

The ability of arginine-rich peptides to cross the lipid bilayer and enter cytoplasm, unlike their lysine-based analogues, is intensively studied in the context of cell-penetrating peptides. Although the experiments have not yet reconstructed their internalization mechanism, the computational studies have shown that the type or charge of lipid polar groups is one of the crucial factors in their translocation. In order to gain more detailed insight into the interaction of guanidinium (Gdm+) and ammonium (NH4+) cations, as important building blocks in arginine and lysine amino acids, with lipid bilayers, we conducted the experimental and computational study that tackles this phenomenon. The adsorption of Gdm+ and NH4+ on lipid bilayers prepared from a zwitterionic (DPPC) and an anionic (DPPS) lipid was examined by thermoanalytic and spectroscopic techniques. Using temperature-dependent UV-Vis spectroscopy and DSC calorimetry we determined the impact of Gdm+ and NH4+ on the thermotropic properties of lipid bilayers. FTIR data, along with molecular dynamics simulations, unraveled the molecular-level details on the nature of their interactions, showing the proton transfer between NH4+ and DPPS, but not between Gdm+ and DPPS. The findings originated from this work imply that Gdm+ and NH4+ form qualitatively different interactions with lipids of different charge which is reflected in the physico-chemical interactions that arginine-and lysine-based peptides establish at a complex and chemically heterogeneous environment such as the biological membrane.

Silver Is Not Equal to Silver: Synthesis and Evaluation of Silver Nanoparticles with Low Biological Activity, and Their Incorporation into C12Alanine-Based Hydrogel.

A new type of silver nanoparticles (AgNPs) was prepared and comprehensively studied. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) analyses indicated that 24 nm AgNPs with narrow size distribution were obtained while Z-potential confirms their good stability. The composites of the obtained AgNPs with nontoxic-nature-inspired hydrogel were formed upon cooling of the aqueous solution AgNPs and C12Ala. The thermal gravimetric analysis (TGA) and the differential scanning calorimetry (DSC) do not show significant shifts in the characteristic temperature peaks for pure and silver-enriched gels, which indicates that AgNPs do not strongly interact with C12Ala fibers, which was also confirmed by SEM. Both AgNPs alone and in the assembly with the gelator C12Ala were almost biologically passive against bacteria, fungus, cancer, and nontumor human cells, as well as zebra-fish embryos. These studies proved that the new inactive AgNPs-doped hydrogels have potential for the application in therapy as drug delivery media.

Authenticity Assessment from Sesame Seeds to Oil and Sesame Products of Various Origin by Differential Scanning Calorimetry.

The aim of this study was to conduct thermal characterization of sesame seeds and oils from various geographical origins (Ethiopia, India, Nigeria, Sudan, Turkey), different method of extraction (hexane and cold-pressing), and different types of derived products (halva and tahini). Thermal characterization was investigated using differential scanning calorimetry (DSC), which showed that origin of the seeds has no influence on the melting profile of sesame oil (peak temperature and enthalpy). Method of extraction (hexane and cold-pressing) influenced the peak temperatures of the resulting oils (p ≤ 0.05). The addition of 20% of palm olein to pure sesame oil influenced the significant changes in thermodynamic parameters such as peak temperature (Tm2), which was lowered from −5.89 °C to −4.99 °C, peak half width (T1/2), elevated from 3.01 °C to 4.52 °C, and the percentage of first peak area (% peak 1) lowered from 87.9 to 73.2% (p ≤ 0.05). The PCA method enabled to distinguish authentic and adulterated sesame oils of various origins. There were no significant differences in thermal properties among the products (halva, tahini) and the authentic sesame oil (p > 0.05). The obtained results showed DSC feasibility to characterize sesame oil and sesame products in terms of authenticity.

Evaluating quality consistency of cigarette by 3 kinds of quantum fingerprints.

Cigarette has a history of more than 40 years and once sold well all over the country. The purpose of this paper is to evaluate the quality consistency of 30 batches of cigarettes. Differential scanning calorimetry (DSC) curves, Fourier Transform Infrared (FT-IR) spectra and terahertz time-domain spectra of 30 batches of cigarettes were collected. In this paper, a new quality evaluation method was explored, the obtained fingerprints were quantized, the t-test was used to analyze the correlation between the original fingerprint and the quantum fingerprint. The quantized fingerprints were evaluated by the systematically quantitative fingerprint method (SQFM), the macro qualitative similarity and the macro quantitative similarity were used to reflect the internal differences of the samples. Finally, the antioxidant activities of 30 batches of samples were investigated, and the correlation between quantum fingerprints and IC50 values were analyzed by Pearson correlation coefficient (r).The result shows that there was no significant difference between the quantum fingerprint and the original fingerprint; SQFM can effectively calculate the similarity of sample curves and classify samples into different grades; the FT-IR fingerprints had a good correlation with the IC50 value. 30 samples performed a good quality consistency within an acceptable grades range. In addition, quantum fingerprints have broad application prospects in spectral analysis.

Microscopic and Spectroscopic Imaging and Thermal Analysis of Acrylates, Silicones and Active Pharmaceutical Ingredients in Adhesive Transdermal Patches.

Dermal or transdermal patches are increasingly becoming a noteworthy alternative as carriers for active pharmaceutical ingredients (APIs), which makes their detailed physicochemical evaluation essential for pharmaceutical development. This paper demonstrates mid-infrared (FTIR) and Raman spectroscopy with complementary microscopic methods (SEM, optical and confocal Raman microscopy) and differential scanning calorimetry (DSC) as tools for the identification of the state of model API (testosterone TST, cytisine CYT or indomethacin IND) in selected adhesive matrices. Among the employed spectroscopic techniques, FTIR and Raman may be used not only as standard methods for API identification in the matrix, but also as a means of distinguishing commercially available polymeric materials of a similar chemical structures. A novel approach for the preparation of adhesive polymers for the FTIR analysis was introduced. In silicone matrices, all three APIs were suspended, whereas in the case of the acrylic PSA, Raman microscopy confirmed that only IND was dissolved in all three acrylic matrices, and the dissolved fraction of the CYT differed depending on the matrix type. Moreover, the recrystallization of TST was observed in one of the acrylates. Interestingly, a DSC analysis of the acrylic patches did not confirm the presence of the API even if the microscopic images showed suspended particles.

The era of fake medicines: Investigating counterfeit medicinal products for erectile dysfunction disguised asherbal supplements.

Sales of substandard and falsified medical products (SF) are rising rapidly everywhere around the globe. The wide and easy access to these products is an alarming issue to the global health systems and undermined the health of patients, especially with the thrive of online commerce. To tackle this threat to public health, new ways to access these products should be identified and detection technologies should be strengthened. The overarching aim of this study was to investigate if herbal supplements sold online claiming to be natural alternatives to Viagra® were amongst these SF medical products and how effective different analytical techniques are in providing information about these products. 3 products which claimed to be herbal supplements for men sexual performance were purchased from an e-commerce platform. Two products were received as unregistered generic sildenafil citrate tablets manufactured in India (and thus different to the products information on the website) while one product was received in the same packaging as shown on the website, claiming to be an herbal product. Nevertheless, all products were proven to contain sildenafil citrate, the active pharmaceutical ingredients in Viagra® after the comprehensive analytical tests. The results elucidated that the quality standards for the unregistered generic sildenafil citrate tablets were fulfilled according to the British Pharmacopeia, but the falsified product failed the quality tests and contained approximately 200 mg sildenafil citrate, which is equivalent to 2-fold of the daily maximum dose. Furthermore, physical characterisations, including powder x-ray diffraction and thermal analysis were performed and revealed that the polymorphic forms of sildenafil citrate were different, demonstrating the importance of employing thermal analysis in addition to the conventional analysis techniques for the substandard and falsified medical products. These techniques provided valuable insights into the physical form of the active ingredient in these products. What is more, the ease with which these SF products were obtained and confirmed to be misleading consumers emphasises the need for tighter regulation for e-commerce websites in line with those enforced on online pharmacies.

Hemisynthesis of coumarin derivatives from Ammodaucus leucotrichus oil extract: organobase-catalyzed reaction, analytical study by diffusion-ordered spectroscopy NMR and differential scanning calorimetry.

This paper presents an in-depth chemical and analytical study of a natural substance extracted from Ammodaucus leucotrichus Coss. & Dur and its derivatives after hemisynthesis. The analysis was performed using Diffusion-Ordered Spectroscopy (NMR DOSY) and Differential Scanning Calorimetry (DSC) as general methods. The results show an interesting chemical reactivity towards coumarin-derived bisnucleophiles (4-hydroxycoumarin and triacetic acid lactone), and products obtained by hemisynthesis of pyrano[4,3-b]pyrane derivatives following Knoevenagel condensation and Michael's addition on this natural substance with the use of 4-pyrolidinopyridine organobase as catalyst.

Interrater agreement of contouring of the neurovascular bundles and internal pudendal arteries in neurovascular-sparing magnetic resonance-guided radiotherapy for localized prostate cancer.

BACKGROUND AND PURPOSE: Radiation damage to neural and vascular tissue, such as the neurovascular bundles (NVBs) and internal pudendal arteries (IPAs), during radiotherapy for prostate cancer (PCa) may cause erectile dysfunction. Neurovascular-sparing magnetic resonance-guided adaptive radiotherapy (MRgRT) aims to preserve erectile function after treatment. However, the NVBs and IPAs are not routinely contoured in current radiotherapy practice. Before neurovascular-sparing MRgRT for PCa can be implemented, the interrater agreement of the contouring of the NVBs and IPAs on pre-treatment MRI needs to be assessed. MATERIALS AND METHODS: Four radiation oncologists independently contoured the prostate, NVB, and IPA in an unselected consecutive series of 15 PCa patients, on pre-treatment MRI. Dice similarity coefficients (DSCs) for pairwise interrater agreement of contours were calculated. Additionally, the DCS of a subset of the inferior half of the NVB contours (i.e. approximately prostate midgland to apex level) was calculated. RESULTS: Median overall interrater DSC for the left and right NVB was 0.60 (IQR: 0.54 - 0.68) and 0.61 (IQR: 0.53 - 0.69) respectively and for the left and right IPA 0.59 (IQR: 0.53 - 0.64) and 0.59 (IQR: 0.52 - 0.64) respectively. Median overall interrater DSC for the inferior half of the left NVB was 0.67 (IQR: 0.58 - 0.74) and 0.67 (IQR: 0.61 - 0.71) for the right NVB. CONCLUSION: We found that the interrater agreement for the contouring of the NVB and IPA improved with enhancement of the MRI sequence as well as further training of the raters. The agreement was best in the subset of the inferior half of the NVB, where a good agreement is clinically most relevant for neurovascular-sparing MRgRT for PCa.

Influence of Drying Techniques on the Physicochemical, Nutritional, and Morphological Properties of Bighead Carp (Hypophthalmichthys nobilis) Fillets.

Different experiment analyses were performed to evaluate the influence of two drying techniques (oven drying and microwave drying) on the fillets of bighead carp fish (Hypophthalmichthys nobilis). The processed and fresh samples were subjected to the chemical analysis of (amino acids, minerals, volatile compounds, fatty acids, and vitamins) as well as scanning electron microscopy, thermal analysis, and color measurement, in order to identify nutritional components that can be additives or supplementary in food industries. The drying techniques increased the protein content significantly. Amino acids were identified, and the level of essential amino acid (EAA) was higher under the microwave treatment compared with the oven drying process. The Ca+2 and K+1 were presented in high values, followed by Na+1 and Mg+2. In addition, the drying techniques showed and released more volatile compounds in the processed samples compared with the unprocessed samples. Under the drying process, polyunsaturated fatty acids were increased in the processed fillets, whereas the level of saturated and monounsaturated fatty acids reduced. Thermal degradation occurred from 100 to 150 °C. However, the processed samples were subjected to an intensive endothermic response, but remained stable until 100 °C. Therefore, the microwave technique showed some enhancements in the nutritional value and has the potential to be applied as an effective preservation method of bighead carp fish. Furthermore, dried fillets could be an alternative source of bighead carp fish for the food industry.

Development and Characterization of Calcium-Alginate Beads of Apigenin: In Vitro Antitumor, Antibacterial, and Antioxidant Activities.

The objective of this work was to develop sustained-release Ca-alginate beads of apigenin using sodium alginate, a natural polysaccharide. Six batches were prepared by applying the ionotropic gelation technique, wherein calcium chloride was used as a crosslinking agent. The beads were evaluated for particle size, drug loading, percentage yield, and in vitro drug release. Particle size was found to decrease, and drug entrapment efficiency was enhanced with an increase in the polymer concentration. The dissolution study showed sustained drug release from the apigenin-loaded alginate beads with an increase in the polymer proportion. Based on the dissolution profiles, BD6 formulation was optimized and characterized for FTIR, DSC, XRD, and SEM, results of which indicated successful development of apigenin-loaded Ca alginate beads. MTT assay demonstrated a potential anticancer effect against the breast cancer MCF-7 cell lines. The antimicrobial activity exhibited effective inhibition in the bacterial and fungal growth rate. The DPPH measurement revealed that the formulation had substantial antioxidant activity, with EC50 value slightly lowered compared to pure apigenin. A stability study demonstrated that the BD6 was stable with similar (f2) drug release profiles in harsh condition. In conclusion, alginate-based beads could be used for sustaining the drug release of poorly water-soluble apigenin while also improving in vitro antitumor, antimicrobial, and antioxidant activity.

Isobavachalcone as an Active Membrane Perturbing Agent and Inhibitor of ABCB1 Multidrug Transporter.

Isobavachalcone (IBC) is an active substance from the medicinal plant Psoralea corylifolia. This prenylated chalcone was reported to possess antioxidative, anti-inflammatory, antibacterial, and anticancer activities. Multidrug resistance (MDR) associated with the over-expression of the transporters of vast substrate specificity such as ABCB1 (P-glycoprotein) belongs to the main causes of cancer chemotherapy failure. The cytotoxic, MDR reversing, and ABCB1-inhibiting potency of isobavachalcone was studied in two cellular models: human colorectal adenocarcinoma HT29 cell line and its resistant counterpart HT29/Dx in which doxorubicin resistance was induced by prolonged drug treatment, and the variant of MDCK cells transfected with the human gene encoding ABCB1. Because MDR modulators are frequently membrane-active substances, the interaction of isobavachalcone with model phosphatidylcholine bilayers was studied by means of differential scanning calorimetry. Molecular modeling was employed to characterize the process of membrane permeation by isobavachalcone. IBC interacted with ABCB1 transporter, being a substrate and/or competitive inhibitor of ABCB1. Moreover, IBC intercalated into model membranes, significantly affecting the parameters of their main phospholipid phase transition. It was concluded that isobavachalcone interfered both with the lipid phase of cellular membrane and with ABCB1 transporter, and for this reason, its activity in MDR cancer cells was presumptively beneficial.

Pulmonary Delivery of Curcumin and Beclomethasone Dipropionate in a Multicomponent Nanosuspension for the Treatment of Bronchial Asthma.

Curcumin has shown a potential extraordinary activity as an add-on ingredient in asthma treatment, due to its immunomodulatory and anti-inflammatory mechanism of action. However, its low water solubility and bioavailability lead to a poor therapeutic effect, which can be overcome by its formulation as nanocrystals. The aim of this study was to prepare a multicomponent formulation for the delivery of curcumin (CUR) and beclomethasone dipropionate (BDP) into the lungs as water-based nanosuspensions (NS). Single component formulations (CUR-NS, BDP-NS) and a multicomponent formulation (CUR+BDP-NS) were prepared through a wet ball media milling technique, using P188 as a non-toxic stabilizer. Characterization was carried out in terms of size, size distribution, zeta potential, nanocrystals morphology, and solid-state properties. Moreover, the inhalation delivery efficiency was studied with Next Generation Impactor (NGI, Apparatus E Ph. Eu). CUR-NS was optimized and showed a long-term stability and improved nanocrystals apparent solubility. The three formulations exhibited a nanocrystal mean diameter in the range of 200-240 nm and a homogenous particle size distribution. Aggregation or sedimentation phenomena were not observed in the multicomponent formulation on 90 days storage at room temperature. Finally, the nebulization tests of the three samples showed optimal aerodynamic parameters and MMAD < 5 µm.

Unusual antibiotic resistance pattern among blood culture isolates of Salmonella Paratyphi A.

INTRODUCTION: With increasing fluoroquinolone resistance, extended spectrum cephalosporins are recommended for the treatment of invasive Salmonella infections. However, Extended spectrum beta-lactamases (ESBL) producing Salmonella Paratyphi A causing enteric fever is on the rise and constitutes a major therapeutic challenge. Hence, we aimed to assess the incidence of ESBL production, fluoroquinolone resistance in S. Paratyphi A and to compare the fluoroquinolone resistance detection methods. METHODOLOGY: Seventeen blood-culture isolates of S. Paratyphi A were tested for susceptibility to ampicillin, chloramphenicol, co-trimoxazole, streptomycin and tetracycline (ACCuST), fluoroquinolones, azithromycin and ceftriaxone by disk diffusion method. We compared and correlated between disk diffusion of ciprofloxacin and pefloxacin with ciprofloxacin MIC. Combined disk test was employed to determine ESBL production. RESULTS: In this study, 13(76.5%) isolates were nalidixic acid resistant (NAR), 16 (94.1%) were pefloxacin resistant, while 7 (41.2%), 9 (52.9%) exhibited resistance and intermediate susceptibility to ciprofloxacin respectively. The MIC50, MIC90 of ciprofloxacin was 1 µg/mL, 2 µg/mL respectively. Among the NAR, 76.92% were DSC (MIC 0.5-1 µg/mL) and 23.08% had an MIC of 2-4 µg/mL. Of note, 4 isolates with DSC were NAS. Of the 17 S. Paratyphi A isolates, 14 (82.4%) were ESBL producers and 11 (64.7%) isolates were ceftriaxone susceptible. CONCLUSIONS: Multidrug resistant (AmpRChlRSxtR) S. Paratyphi A with combined resistance to fluoroquinolones and ESBL production is a cause of concern. We found S. Paratyphi A isolates with a relatively unusual phenotype: nalidixic acid susceptible but exhibited DSC; pefloxacin susceptible but ciprofloxacin resistant. Of note one multidrug resistant (AmpRChlRSxtR) isolate, an ESBL producer exhibited resistance to azithromycin, cephalosporins and fluoroquinolones but was susceptible to carbapenems and streptomycin.

Structural, Thermal, and Storage Stability of Rapana Thomasiana Hemocyanin in the Presence of Cholinium-Amino Acid-Based Ionic Liquids.

Novel biocompatible compounds that stabilize proteins in solution are in demand for biomedical and/or biotechnological applications. Here, we evaluated the effect of six ionic liquids, containing mono- or dicholinium [Chol]1or2 cation and anions of charged amino acids such as lysine [Lys], arginine [Arg], aspartic acid [Asp], or glutamic acid [Glu], on the structure, thermal, and storage stability of the Rapana thomasiana hemocyanin (RtH). RtH is a protein with huge biomedicinal potential due to its therapeutic, drug carrier, and adjuvant properties. Overall, the ionic liquids (ILs) induce changes in the secondary structure of RtH. However, the structure near the Cu-active site seems unaltered and the oxygen-binding capacity of the protein is preserved. The ILs showed weak antibacterial activity when tested against three Gram-negative and three Gram-positive bacterial strains. On the contrary, [Chol][Arg] and [Chol][Lys] exhibited high anti-biofilm activity against E. coli 25213 and S. aureus 29213 strains. In addition, the two ILs were able to protect RtH from chemical and microbiological degradation. Maintained or enhanced thermal stability of RtH was observed in the presence of all ILs tested, except for RtH-[Chol]2[Glu].