In Vitro Tests of FDM 3D-Printed Diclofenac Sodium-Containing Implants.

One of the most promising emerging innovations in personalized medication is based on 3D printing technology. For use as authorized medications, 3D-printed products require different in vitro tests, including dissolution and biocompatibility investigations. Our objective was to manufacture implantable drug delivery systems using fused deposition modeling, and in vitro tests were performed for the assessment of these products. Polylactic acid, antibacterial polylactic acid, polyethylene terephthalate glycol, and poly(methyl methacrylate) filaments were selected, and samples with 16, 19, or 22 mm diameters and 0%, 5%, 10%, or 15% infill percentages were produced. The dissolution test was performed by a USP dissolution apparatus 1. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide dye (MTT)-based prolonged cytotoxicity test was performed on Caco-2 cells to certify the cytocompatibility properties. The implantable drug delivery systems were characterized by thermogravimetric and heatflow assay, contact angle measurement, scanning electron microscopy, microcomputed tomography, and Raman spectroscopy. Based on our results, it can be stated that the samples are considered nontoxic. The dissolution profiles are influenced by the material properties of the polymers, the diameter, and the infill percentage. Our results confirm the potential of fused deposition modeling (FDM) 3D printing for the manufacturing of different implantable drug delivery systems in personalized medicine and may be applied during surgical interventions.

In Vivo evaluation of newly synthesized 213Bi-conjugated alpha-melanocyte stimulating hormone (α-MSH) peptide analogues in melanocortin-1 receptor (MC1-R) positive experimental melanoma model.

Given the rising pervasiveness of melanocortin-1 receptor (MC1-R) positive melanoma malignum (MM) and pertinent metastases, radiolabelled receptor-affine alpha-melanocyte stimulating hormone-analogue (α-MSH analogue) imaging probes would be of crucial importance in timely tumor diagnostic assessment. Herein we aimed at investigating the biodistribution and the MM targeting potential of newly synthesized 213Bi-conjugated MC1-R specific peptide-based radioligands with the establishment of MC1-R overexpressing MM preclinical model. DOTA-conjugated NAP, -HOLD, -FOLD, -and MARSamide were labelled with 213Bi. Ex vivo biodistribution studies were conducted post-administration of 3.81 ± 0.32 MBq [213Bi]Bi-DOTA conjugated deriva-tives into twenty B16-F10 tumor-bearing C57BL/6 J and healthy mice. Organ Level Internal Dose Assessment (OLINDA) and IDAC-Dose were used to calculate translational data-based absorbed radiation dose in human organs. Moderate or low %ID/g uptake of [213Bi]Bi-DOTA conjugated NAP, -HOLD, -and MARSamide and significantly increased [213Bi]Bi-DOTA-FOLDamide accumulation was observed in the thoracic and abdominal organs (p ≤ 0.01). High [213Bi]Bi-DOTA-NAP (%ID/g:3.76 ± 0.96), -and FOLDamide (%ID/g:3.28 ± 0.95) tumor tracer activity confirmed their MC1-R-affinity. The bladder wall received the highest radiation absorbed dose followed by the kidneys (bladder wall: 1.95·10-2 and 8.97·10-2 mSv/MBq; kidneys: 7.47·10-3 vs. 5.88·10-2 mSv/MBq measured by IDAC and OLINDA; respectively) indicating the suitability of the NAPamide derivative for clinical use. These novel [213Bi]Bi-DOTA-linked peptide probes displaying meaningful MC1-R affinity could be promising molecular probes in MM imaging.

Sulfur(IV) assisted oxidative removal of organic pollutants from source water.

The removal of organic pollutants presents a major challenge for drinking water treatment plants. The chemical oxygen demand (COD) is essentially the measure of oxidizable organic matter in source waters. In this study, we report that COD can efficiently be decreased by adding Fe(II)/Fe(III) and sulfite ion to the source water while purging it with air. In this process, oxygen is activated to oxidize the main constituents of COD, i.e. organic substrates, via the generation of reactive inorganic oxysulfur radical ions. In the end, the total amount of sulfur(IV) is converted to the non-toxic sulfate ion. It has been explored how the COD removal efficiency depends on the concentration of S(IV), the total concentration of iron species, the concentration ratio of Fe(II) and Fe(III), the purging rate and the contact time by using source water from a specific location (Királyhegyes, Hungary). The process has been optimized by applying the Response Surface Methodology (RSM). Under optimum conditions, the predicted and experimentally found COD removal efficiencies are in excellent agreement: 85.4% and 87.5%, respectively. The robustness of the process was tested by varying the optimum values of the parameters by ± 20%. It was demonstrated that the method is universally applicable because a remarkable decrease was achieved in COD, 62.0-88.5%, with source waters of various compositions acquired from 9 wells at other locations using the same conditions as in the case of Királyhegyes.

High-Resolution Dynamics of Hemodilution After Exercise-Related Hemoconcentration.

PURPOSE: Hemoconcentration during acute intense exercise is intensively investigated, while the rearrangement of hematological parameters during the recovery period is less understood. The aim of our study was to understand the mechanisms of hemodilution after short-term dynamic exercise. METHODS: Twelve euhydrated male kayak athletes and 6 untrained controls were examined on a spiroergometer. In addition to the continuous recording of circulatory parameters, blood samples were taken at rest, at maximum load, and during restitution with a dense sampling frequency. Hemoglobin, hematocrit, osmolality, blood components, and core temperature were measured. RESULTS: The hemoconcentration, independently of training status, reached its maximum (athletes Δ9.59% [4.18%] vs controls Δ11.85% [2.71%]) in the first minute of the recovery period. There was a significant increase in core temperature, reducing the viscosity of blood and promoting tissue oxygenation. High cardiac output and the increased blood flow compensate for viscosity being elevated by hemoconcentration during exercise. Hemoconcentration was maintained for 7 to 10 minutes and then diluted back to baseline 30 minutes after exercise. Temporarily higher viscosity during reduced cardiac output may result in a critical hemoconcentration zone, elevating the risk of circulatory overload. Elite athletes have a faster cardiac output decrease compared with that of hemodilution, making the circulation more vulnerable. We supposed that hemodilution was guided independently by plasma- and erythrocyte-related effectors. CONCLUSIONS: After high-intensity dynamic acute exercise, hemodilution is driven by independent factors, and a critical hemoconcentration zone may be formed during the recovery period in trained elite athletes.

Exercise-related hemoconcentration and hemodilution in hydrated and dehydrated athletes: An observational study of the Hungarian canoeists.

Hemoconcentration during exercise is a well-known phenomenon, however, the extent to which dehydration is involved is unclear. In our study, the effect of dehydration on exercise-induced hemoconcentration was examined in 12 elite Hungarian kayak-canoe athletes. The changes of blood markers were examined during acute maximal workload in hydrated and dehydrated states. Dehydration was achieved by exercise, during a 120-minute extensive-aerobic preload. Our research is one of the first studies in which the changes in blood components were examined with a higher time resolution and a wider range of the measured parameters. Hydration status had no effect on the dynamics of hemoconcentration during both the hydrated (HS) and dehydrated (DHS) load, although lower maximal power output were measured after the 120-minute preload [HS Hemoglobin(Hgb)Max median 17.4 (q1 17.03; q3 17.9) g/dl vs. DHS HgbMax median 16.9 (q1 16.43; q3 17.6) g/dl (n.s); HS Hematocrit(Hct)Max 53.50 (q1 52.28; q3 54.8) % vs. DHS HctMax 51.90 (q1 50.35; q3 53.93) % (n.s)]. Thirty minutes after the maximal loading, complete hemodilution was confirmed in both exercises. Dehydration had no effect on hemoconcentration or hemodilution in the recovery period [HS HgbR30' 15.7 (q1 15.15; q3 16.05) g/dl (n.s.) vs. DHS HgbR30' 15.75 (q1 15.48; q3 16.13) g/dl (n.s.), HS HctR30' 48.15 (q1 46.5; q3 49.2) % vs. DHS HctR30' 48.25 (q1 47.48; q3 49.45) % (n.s.)], however, plasma osmolality did not follow a corresponding decrease in hemoglobin and hematocrit in the dehydrated group. Based on our data, metabolic products (glucose, lactate, sodium, potassium, chloride, bicarbonate ion, blood urea nitrogen) induced osmolality may not play a major role in the regulation of hemoconcentration and post-exercise hemodilution. From our results, we can conclude that hemoconcentration depends mainly on the intensity of the exercise.

Enantioselective capillary electrophoretic separation of tryptophane- and tyrosine-methylesters in a dual system with a tetra-oxadiaza-crown-ether derivative and a cyclodextrin.

Different dual selector systems containing a cyclodextrin derivative (methyl-beta-cyclodextrin and dimethyl-beta-cyclodextrin) and a new diaza-crown-ether derivative (N-[2-(1,4,10,13-tetraoxa-7,16-diazacyclooctadecan-7-yl)propanoyl]glycine) were studied in the enantioselective separation of tryptophan-methylester and tyrosine-methylester enantiomers. This paper deals with the systematic study of the effects of changing the composition of the background electrolyte on the resolution of the d- and l- forms using an experimental design approach. It was found that the dual systems allowed a better chiral separation of the amino acid derivatives. The experimental design approach also allowed improving the separation compared to the starting conditions (center point of the design), which were adopted from a previous study.