Comparative Evaluation of Sucrosomial Iron and Iron Oxide Nanoparticles as Oral Supplements in Iron Deficiency Anemia in Piglets

Iron deficiency is the most common mammalian nutritional disorder. However, among mammalian species iron deficiency anemia (IDA), occurs regularly only in pigs. To cure IDA, piglets are routinely injected with high amounts of iron dextran (FeDex), which can lead to perturbations in iron homeostasis. Here, we evaluate the therapeutic efficacy of non-invasive supplementation with Sucrosomial iron (SI), a highly bioavailable iron supplement preventing IDA in humans and mice and various iron oxide nanoparticles (IONPs). Analysis of red blood cell indices and plasma iron parameters shows that not all iron preparations used in the study efficiently counteracted IDA comparable to FeDex-based supplementation. We found no signs of iron toxicity of any tested iron compounds, as evaluated based on the measurement of several toxicological markers that could indicate the occurrence of oxidative stress or inflammation. Neither SI nor IONPs increased hepcidin expression with alterations in ferroportin (FPN) protein level. Finally, the analysis of the piglet gut microbiota indicates the individual pattern of bacterial diversity across taxonomic levels, independent of the type of supplementation. In light of our results, SI but not IONPs used in the experiment emerges as a promising nutritional iron supplement, with a high potential to correct IDA in piglets.     

Hapten Design for Antibody-Catalyzed Decarboxylation and Ring-Opening Reactions of Benzisoxazoles

Three benzisoxazole haptens designed to elicit antibody binding sites with widely differing polarity have been synthesized and used to induce antibodies in mice. Monoclonal antibodies were prepared using hybridoma technology, and screened for catalysis of the ring-opening isomerization and/or decarboxylation of a series of related benzisoxazoles and their 3-carboxy-derivatives. No catalysis of decarboxylation was observed, but 4 of a total of 47 antibodies obtained against the three haptens catalyzed the isomerization process. Of 12 antibodies raised against the 3-acetylbenzisoxazole structure 5 none was catalytically active; but one of 24 raised against a 3-isopropenylbenzisoxazole 6 increased the rate of ring-opening of 6-nitrobenzisoxazole, and 5 of 11 antibodies raised against a benzisoxazole 7 with a 3-amidinium group were moderately active against either 6-nitro or 6-acylaminobenzisoxazoles. Competitive binding studies suggest that at least some of the antibodies induced by the isopropenyl hapten do possess a recognizably hydrophobic binding site.     

Impact of SGLT-2 Inhibition on Cardiometabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have a high prevalence of obesity, insulin resistance (IR), increased blood pressure (BP), and activation of the renin angiotensin system (RAS). Effective evidence-based therapeutics to ameliorate the cardiometabolic complications in PCOS are lacking. The sodium-glucose cotransporter-2 (SGLT2) inhibitor Empagliflozin (EMPA) reduces BP and hyperglycemia in type 2 diabetes mellitus. We hypothesized that hyperandrogenemia upregulates renal SGLT2 expression and that EMPA ameliorates cardiometabolic complications in a hyperandrogenemic PCOS model. Four-week-old female Sprague Dawley rats were treated with dihydrotestosterone (DHT) for 90 days, and EMPA was co-administered for the last three weeks. DHT upregulated renal SGLT2, SGLT4, and GLUT2, but downregulated SGLT3 mRNA expression. EMPA decreased DHT-mediated increases in fat mass, plasma leptin, and BP, but failed to decrease plasma insulin, HbA1c, or albuminuria. EMPA decreased DHT-mediated increase in renal angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE2), and angiotensin II type 1 receptor (AGT1R) mRNA and protein expression. In summary, SGLT2 inhibition proved beneficial in adiposity and BP reduction in a hyperandrogenemic PCOS model; however, additional therapies may be needed to improve IR and renal injury.     

Muscarinic Acetylcholine Receptors in the Retina—Therapeutic Implications

Muscarinic acetylcholine receptors (mAChRs) belong to the superfamily of G-protein-coupled receptors (GPCRs). The family of mAChRs is composed of five subtypes, M₁, M₂, M₃, M₄ and M₅, which have distinct expression patterns and functions. In the eye and its adnexa, mAChRs are widely expressed and exert multiple functions, such as modulation of tear secretion, regulation of pupil size, modulation of intraocular pressure, participation in cell-to-cell signaling and modula-tion of vascular diameter in the retina. Due to this variety of functions, it is reasonable to assume that abnormalities in mAChR signaling may contribute to the development of various ocular diseases. On the other hand, mAChRs may offer an attractive therapeutic target to treat ocular diseases. Thus far, non-subtype-selective mAChR ligands have been used in ophthalmology to treat dry eye disease, myopia and glaucoma. However, these drugs were shown to cause various side-effects. Thus, the use of subtype-selective ligands would be useful to circumvent this problem. In this review, we give an overview on the localization and on the functional role of mAChR subtypes in the eye and its adnexa with a special focus on the retina. Moreover, we describe the pathophysiological role of mAChRs in retinal diseases and discuss potential therapeutic approaches.     

BiFeO3-synthesis,characterization and its photocatalytic activity towards doxorubicin degradation from water

Pure bismuth ferrite was successfully obtained through the thermolysis of new bismuth ferrioxalate coordination compound, namely BiFe(C₂O₄)₃·3H₂O. The synthesized precursor was characterized by chemical analysis, infrared spectroscopy and thermal analysis. The bismuth ferrite obtained after a heating treatment of the precursor for at 450–800?°C/1?h was investigated by X-ray diffraction, FE-SEM, TEM and HRTEM. The obtained pure bismuth ferrite nanoparticles (480?°C) was tested as photocatalyst towards the degradation of doxorubicin (DOX), a well-known anti-cancer drug commonly used for the treatment of various cancer types, which has been detected in hospital effluent water. The comparative results of DOX degradation through photolysis and photocatalysis under UV irradiation showed a great photocatalytic activity of bismuth ferrite towards DOX degradation and mineralization from water. The kinetics aspects were discussed based on the first-order kinetics model that fitted the best the experimental photocatalysis results.     

Boron Carbide–Zirconium Boride In Situ Composites by the Reactive Pressureless Sintering of Boron Carbide–Zirconia Mixtures

The heating of B₄C–YTZP (where YTZP denotes yttria-stabilized zirconia polycrystals) mixtures, under an argon atmosphere, generates B₄C–ZrB₂ composites, because of a low-temperature (<1500°C) carbide–oxide reaction. Composites derived from mixtures that include ≥15% YTZP are better sintered than monolithic B₄C that has been fired under the same conditions. Firing to ∼2160°C (1 h dwell) generates specimens with a bulk density of ≥91% of the theoretical density (TD) for cases where the initial mixture includes ≥15% YTZP. Mixtures that include 30% YTZP allow a fired density of ≥97.5% TD to be attained. The behavior of the B₄C–YTZP system is similar to that of the B₄C–TiO₂ system. Dense B₄C–ZrB₂ composites attain a hardness (Vickers) of 30–33 GPa.     

A new two-stage curing system: Thiol-ene/epoxy homopolymerization using an allyl terminated hyperbranched polyester as reactive modifier

An allyl terminated hyperbranched polyester (HBP) was added to an epoxy formulation containing a trithiol compound to perform a thiol-ene click reaction. By this procedure a flexible thioether network was formed. The photoirradiation of the reactive mixture, which contained a cationic photoinitiator, converted the thioether network in a multifunctional thermal macroinitiator, capable to initiate the cure of the cycloaliphatic epoxy resin(CE) in a second thermal stage. Depending on the proportion of HBP, thermal or photocuring of the epoxy resin took place in different extent, leading to networks with different structures. The photocuring procedure was followed by FTIR and the thermal second stage by DSC. The materials obtained were characterized by DMTA, TGA and SEM. The addition of HBP-Allyl and the trithiol to the formulation allowed increasing the T_g on comparison with the neat epoxy thermoset. The system proposed constitutes a new two-stage dual photo-thermal curing procedure for cycloaliphatic epoxy resins with a thermal latent character.     

Experiments and dynamic modeling of a reactive distillation column for the production of ethyl acetate by considering the heterogeneous catalyst pilot complexities

Great effort has been applied to model and simulate the dynamic behavior of the reactive distillation as a successful process intensification example. However, very little experimental work has been carried out in transient conditions. The work presents a series of experiments for the production of ethyl acetate from esterification of acetic acid and ethanol in a reactive distillation pilot column. The steady-state approach performed experiments with both excess of alcohol and stoichiometric feed configuration. Predicted and measured results show good agreement and reveal a strong dependency of the structured packing catalyst activity on the pilot geometry and its operating conditions. The transient process behavior of the heterogeneously catalyzed system was deeply investigated and continuous and dynamic data were collected for an equilibrium model validation, after different perturbations on parameters. The experimental validation is shown to be essential to provide realistic hydrodynamic parameters, to understand the sensitive parameters such as heat losses and to adapt values for the catalyst holdup as a function of the system.     

Which separation scenarios are advantageous for membranes or distillations?

We systematically analyze power requirements of membrane and distillation processes for binary mixtures where the desired product component is more permeable and also more volatile. We first derive a shortcut method to compare the efficiency of heat pump and steam-driven distillations. Then, power requirements of heat pump distillation and membrane separation are discussed. Distillation generally requires lower power when either high component recoveries are needed (at all tested product purities), or high purity product streams with modest recoveries are needed. For high purity products at modest recoveries, membranes have a potential to provide energy benefits for highly enriched feeds, especially those composed of close boiling components. Additionally, when feed concentration is moderate to high and product recovery and purity are modest, membranes are likely to show efficiency gain. For the advantageous distillation scenarios studied, the power was generally lower than the membranes by a factor of two to seven.