Hydrosoluble and Liposoluble Vitamins: New Perspectives through ADMET Analysis.

Background and Objectives: The present study demonstrates that apart from the well-known toxicity of liposoluble vitamins, some hydrosoluble vitamins may also exert toxicity; thus, routine supplementation with vitamins or ingestion of fortified foods should not be considered harmless. The study addresses the possible correlations between the physico-chemical properties and the side effects of vitamins when taken in high doses or for a too long a period. Materials and Methods: The FAFDrugs4.0 computational tool was used for computational assessment of the ADMET profile of several hydro- and liposoluble vitamins. Results: ADMET analysis revealed the following major data: vitamin B3 and B13 showed reduced structural complexity; thus, a relative toxicological potential may be exerted. Vitamins B1 and B7 were found to have good oral absorption and thus good bioavailability, while Vitamin B3 was found to have decreased oral absorption. In addition, all of the liposoluble vitamins reflected higher complexity, much greater than most of the potentially therapeutically-proven compounds. Conclusions: The present study emphasizes the importance between the physico-chemical properties of vitamins and their possible toxicological impact.

Development and Characterization of Fe3O4@Carbon Nanoparticles and Their Biological Screening Related to Oral Administration.

The current study presents the effect of naked Fe3O4@Carbon nanoparticles obtained by the combustion method on primary human gingival fibroblasts (HGFs) and primary gingival keratinocytes (PGKs)-relevant cell lines of buccal oral mucosa. In this regard, the objectives of this study were as follows: (i) development via combustion method and characterization of nanosized magnetite particles with carbon on their surface, (ii) biocompatibility assessment of the obtained magnetic nanoparticles on HGF and PGK cell lines and (iii) evaluation of possible irritative reaction of Fe3O4@Carbon nanoparticles on the highly vascularized chorioallantoic membrane of a chick embryo. Physicochemical properties of Fe3O4@Carbon nanoparticles were characterized in terms of phase composition, chemical structure, and polymorphic and molecular interactions of the chemical bonds within the nanomaterial, magnetic measurements, ultrastructure, morphology, and elemental composition. The X-ray diffraction analysis revealed the formation of magnetite as phase pure without any other secondary phases, and Raman spectroscopy exhibit that the pre-formed magnetic nanoparticles were covered with carbon film, resulting from the synthesis method employed. Scanning electron microscopy shown that nanoparticles obtained were uniformly distributed, with a nearly spherical shape with sizes at the nanometric level; iron, oxygen, and carbon were the only elements detected. While biological screening of Fe3O4@Carbon nanoparticles revealed no significant cytotoxic potential on the HGF and PGK cell lines, a slight sign of irritation was observed on a limited area on the chorioallantoic membrane of the chick embryo.

Comparative Toxicological In Vitro and In Ovo Screening of Different Orthodontic Implants Currently Used in Dentistry.

Selecting the most biocompatible orthodontic implant available on the market may be a major challenge, given the wide array of orthodontic devices currently available on the market. The latest scientific data have suggested that in vitro evaluations using oral cell lines provide reliable data regarding the toxicity of residual particles released by different types of orthodontic devices. In this regard, the in vitro biocompatibility of three different commercially available implants (stainless steel and titanium-based implants) was assessed. METHODS: As an in vitro model, human gingival fibroblasts (HGFs) were employed to evaluate the cellular morphology, cell viability, and cytotoxicity by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays at 24 h and 72 h post-exposure to test implants. RESULTS: The results correlate the composition and topography of the implant surface with biological experimental evaluations related to directly affected cells (gingival fibroblasts) and toxicological results on blood vessels (hen's egg test-chorioallantoic membrane (HET-CAM) assay). The stainless steel implant exhibits a relative cytotoxicity against HGF cells, while the other two samples induced no significant alterations of HGF cells. CONCLUSION: Among the three test orthodontic implants, the stainless steel implant induced slight cytotoxic effects, thus increased vigilance is required in their clinical use, especially in patients with high sensitivity to nickel.

Correlations on Phenolic Screening Related to In Vitro and In Ovo Assessment of Ocimum basilicum L. Hydro-Alcoholic Extracts Used as Skin Active Ingredient.

The current study was aimed to evaluate the phenolic composition parameters of two hydro-alcoholic extracts of Ocimum basilicum L. (OB) obtained from the aerial part (without leaves) and leaves, in order to determine their contribution to the antioxidant activity (AOA). Both hydro-alcoholic extracts have proven to be rich in polyphenolic compounds, flavonoids, flavonols and tannins. Therefore, the leaves' extracts reveal an inhibition percentage of 89%, almost comparable with the standard reference (95%). To complete the toxicological profile, the study also assessed the potential cytotoxicity of basil hydro-alcoholic extracts on immortalized human keratinocytes (HaCaT), skin human fibroblasts (1BR3), mice epidermis (JB6Cl41-5a) and primary human melanocytes (HEMa) cells, correlated to A375 antitumor in vitro activity. The extracts did not induce significant cytotoxic effect on any of the selected normal cell lines but showed relevant activity on A375 cells. Considering the low values obtained regarding the irritative effects in the chorionallantoic membrane of the egg on blood vessels, we can emphasize that both extracts can be considered as biocompatible ingredients. Regarding the potential activity of hydro-alcoholic extracts on human skin, the decrease of erythema values after the application of extracts was a relevant observation which indicates the anti-inflammatory potential of Ocimum basilicum L.

Morphology of the GdVO4 crystal: first-principles studies.

The present paper reports a theoretical investigation based on first-principles density functional theory calculations to predict the external morphology of the tetragonal GdVO4 crystal from its internal structure. The Bravais-Friedel-Donnay-Harker (BFDH) method, attachment energy (AE) method and surface energy (SE) method were used in this study. Slice energies (cohesive, attachment and specific surface) of the three main crystal faces having (110), (101) and (200) orientation and their dhkl thicknesses were computed using CRYSTAL17 code, in the frame of a 2D periodic slab model. The relative growth rate (Rhkl) and the morphological importance (MIhkl) for each unrelaxed and relaxed (hkl) face of interest were determined. Consequently, the crystal shapes predicted based upon BFDH, AE and SE methods were represented by the Wulff construction. The results of the morphology crystal predictions, based on the above methods, were compared both against each other and against the experimentally observed morphologies. A quite satisfactory agreement between the predicted and observed crystal morphologies is noticed.

A Custom-Made Orthodontic Mini-Implant-Effect of Insertion Angle and Cortical Bone Thickness on Stress Distribution with a Complex In Vitro and In Vivo Biosafety Profile.

BACKGROUND: Orthodontic mini-implant failure is a debatable subject in clinical practice. However, the most important parameter to evaluate the success rate of mini-implant is the primary stability, which is mainly influenced by cortical bone thickness (CBT) and insertion angle. MATERIALS AND METHODS: Three-dimensional finite element models of the maxilla were created and a custom-made, self-drilling, tapered mini-implant was designed. For the pull-out test, 12 simulations were performed, sequentially increasing the thickness of the cortical bone (1, 1.5 and 2 mm) and the insertion angle (30°, 60°, 90°, 120°). For the force analysis, 24 simulations were performed using an experimental orthodontic traction force of 2 N both in the horizontal and vertical axis. RESULTS: Insertion angle and CBT have significant impact on force reaction values (p < 0.05). Cortical bone stress had the lowest value when the mini-implant had a 30° insertion angle and the highest value when the implant had a 120° insertion angle, while the CBT was 1 mm. Cortical bone stress had the lowest value with an insertion angle of 90° and the highest value when the implant was inserted at an angle of 30°, while the CBT was 2 mm independent of the force direction. Regarding the biosafety profile of the mini-implant alloy, the present results reveal that the custom-made mini-implant presents good biocompatibility. CONCLUSIONS: When the CBT is reduced, we recommend inclined insertion while, when the CBT is appropriate, perpendicular insertion is advised.

Cocrystal Formation of Betulinic Acid and Ascorbic Acid: Synthesis, Physico-Chemical Assessment, Antioxidant, and Antiproliferative Activity.

Betulinic acid (BA) was demonstrated to be a very promising anticancer agent against various tumor cell lines such as breast, colon, lung, and brain. Despite its strong cytotoxic effect, betulinic acid exhibits low water solubility, feature that is reflected in its poor bioavailability. To overcome these drawbacks, numerous strategies were conducted to improve its physicochemical and pharmacokinetic profile, among which cocrystalization emerged as a promising approach. Thus, our work consisted in obtaining slowly grown cocrystals of BA and ascorbic acid (BA+VitC) in isopropyl alcohol obtained in a hydrothermal experiment. The newly formed cocrystals were characterized by physico-chemical methods such asSEM, DSC, XRPD, and FT-IR spectroscopy demonstrating BA+VitC cocrystal formation while their antioxidant activity revealed an additive antioxidant effect. To investigate the biological effect, BA+VitC cocrystals were tested on HaCat (immortalized human keratinocytes), B164A5 and B16F0 (murine melanoma), MCF7 and MDA-MB-231 (human breast cancer), and HeLa (cervical cancer) cell lines. Results of BA upon the tested tumor cell lines, after co-crystallization with vitamin C, indicated a superior cytotoxic effect with the preservation of a good selectivity index assumably due to an improved BA water solubility and consequently an optimized bioavailability.

Neutral density filters with Risley prisms: analysis and design.

We achieve the analysis and design of optical attenuators with double-prism neutral density filters. A comparative study is performed on three possible device configurations; only two are presented in the literature but without their design calculus. The characteristic parameters of this optical attenuator with Risley translating prisms for each of the three setups are defined and their analytical expressions are derived: adjustment scale (attenuation range) and interval, minimum transmission coefficient and sensitivity. The setups are compared to select the optimal device, and, from this study, the best solution for double-prism neutral density filters, both from a mechanical and an optical point of view, is determined with two identical, symmetrically movable, no mechanical contact prisms. The design calculus of this optimal device is developed in essential steps. The parameters of the prisms, particularly their angles, are studied to improve the design, and we demonstrate the maximum attenuation range that this type of attenuator can provide.