Surface Engineering Methods for Powder Bed Printed Tablets to Optimize External Smoothness and Facilitate the Application of Different Coatings.

In a previous attempt to achieve ileo-colonic targeting of bovine intestinal alkaline phosphatase (BIAP), we applied a pH-dependent coating, the ColoPulse coating, directly on powder bed printed (PBP) tablets. However, the high surface roughness necessitated an additional sub-coating layer [Nguyen, K. T. T., Pharmaceutics 2022]. In this study, we aimed to find a production method for PBP tablets containing BIAP that allows the direct application of coating systems. Alterations of the printing parameters, binder content, and printing layer height, when combined, were demonstrated to create visually less rough PBP tablets. The addition of ethanol vapor treatment further improved the surface's smoothness significantly. These changes enabled the direct application of the ColoPulse, or enteric coating, without a sub-coating. In vitro release testing showed the desired ileo-colonic release or upper-intestinal release for ColoPulse or enteric-coated tablets, respectively. Tablets containing BIAP, encapsulated within an inulin glass, maintained a high enzymatic activity (over 95%) even after 2 months of storage at 2-8 °C. Importantly, the coating process did not affect the activity of BIAP. In this study, we demonstrate, for the first time, the successful production of PBP tablets with surfaces that are directly coatable with the ColoPulse coating while preserving the stability of the encapsulated biopharmaceutical, BIAP.

Formulation of a 3D Printed Biopharmaceutical: The Development of an Alkaline Phosphatase Containing Tablet with Ileo-Colonic Release Profile to Treat Ulcerative Colitis.

Powder bed printing is a 3D-printing process that creates freeform geometries from powders, with increasing traction for personalized medicine potential. Little is known about its applications for biopharmaceuticals. In this study, the production of tablets containing alkaline phosphatase using powder bed printing for the potential treatment of ulcerative colitis (UC) was investigated, as was the coating of these tablets to obtain ileo-colonic targeting. The printing process was studied, revealing line spacing as a critical factor affecting tablet physical properties when using hydroxypropyl cellulose as the binder. Increasing line spacing yielded tablets with higher porosity. The enzymatic activity of alkaline phosphatase (formulated in inulin glass) remained over 95% after 2 weeks of storage at 45 °C. The subsequent application of a colonic targeting coating required a PEG 1500 sub-coating. In vitro release experiments, using a gastrointestinal simulated system, indicated that the desired ileo-colonic release was achieved. Less than 8% of the methylene blue, a release marker, was released in the terminal ileum phase, followed by a fast release in the colon phase. No significant impact from the coating process on the enzymatic activity was found. These tablets are the first to achieve both biopharmaceutical incorporation in powder bed printed tablets and ileo-colonic targeting, thus might be suitable for on-demand patient-centric treatment of UC.

Biotic interactions drive ecosystem responses to exotic plant invaders.

Ecosystem process rates typically increase after plant invasion, but the extent to which this is driven by (i) changes in productivity, (ii) exotic species' traits, or (iii) novel (non-coevolved) biotic interactions has never been quantified. We created communities varying in exotic plant dominance, plant traits, soil biota, and invertebrate herbivores and measured indicators of carbon cycling. Interactions with soil biota and herbivores were the strongest drivers of exotic plant effects, particularly on measures of soil carbon turnover. Moreover, plant traits related to growth and nutrient acquisition explained differences in the ways that exotic plants interacted with novel biota compared with natives. We conclude that novel biological interactions with exotic species are a more important driver of ecosystem transformation than was previously recognized.

Longevity of Bond Strength of an Indirect Composite Resin to Dentin Using Conventional or Self-Adhesive Resin Cementation: Influence of Dentin Pretreatment with TiF4.

The purpose was to evaluate the influence of dentin pretreatment with titanium tetrafluoride (TiF4) on the longevity of bond strength (BS) of an indirect composite to dentin, using conventional resin cementation strategy or a self-adhesive resin cement. Forty third human molars with exposed dentin surfaces were used. The teeth were divided into groups (n = 10), according to the cementation strategy and the presence or absence of pretreatment with TiF4. Microtensile strength testing and failure mode analysis were performed after 24 hours, 180 and 360 days of storage in water. Split-plot ANOVA and Tukey's test showed that BS was significantly higher when the conventional strategy was used, regardless of the time period, and of the application or no application of pretreatment with TiF4 (p ⟨0.0001). When TiF4 was used for both cementing strategies, BS was lower after 360 days (p = 0.0019). Both cementing strategies led to the formation of a shallow hybrid layer, regardless of the presence of TiF4. BS was higher when the conventional cementation strategy was used, regardless of TiF4 pretreatment. TiF4 used as a pretreatment agent associated with different types of resin cementation was unable to maintain adhesive bond strength in the long term.

Vitamin C supplementation has no effect on American bullfrog's immune response.

American bullfrog (Lithobates catesbeianus) is the only species raised in Brazilian commercial frog farms, and the intensive culture of these animals has gained great popularity in Brazil over the past several years. Stress is one of the major obstacles in frog culture. To minimise this problem, the aim of the present study was to investigate the role of added vitamin C in the diet of American bullfrogs as an antistress factor through the assessment of plasma corticosterone, leucocyte levels and macrophage activation in animals raised in confinement. The experimental design was entirely randomised, with six treatments (supplementation of 0, 250, 500, 750, 1000 and 2000 mg of vitamin C/kg of feed) and four replications. The plasma corticosterone level, leucocyte level and macrophage activation were evaluated. It was concluded that vitamin C had no influence on the evaluated parameters due to the possible adaptation of the animals to life in captivity (domestication). The results of this research indicate that farmers should not increase the levels of vitamin C in commercial feeds because this would only enhance production costs.

Tracking viral particles in the intestinal contents of the American bullfrog, Lithobates catesbeianus, by Transmission Electron Microscopy / Pesquisa de partículas virais em conteúdo intestinal de rãs-touro americanas, Lithobates catesbeianus, por meio da microscopia eletrônica de transmissão

Feces are an important viral agent elimination route for infected carrier animals and in aquatic organisms these pathogenic agents can very rapidly propagate due to the habitation environment. The objective of this work is to track viral particles in the intestinal contents of bullfrogs (Lithobates catesbeianus) from five commercial frog farms in the region of Vale do Paraíba, in the State of São Paulo, Brazil, using negative contrast transmission electron microscopy (TEM). The Coronaviridae, Paramyxoviridae, Parvoviridae and Herpesviridae families were observed and photographed in specimens. This work emphasizes the importance of adopting sanitary measures in commercial farms and confirms that observing feces by TEM is an efficient and rapid diagnostic tool for detecting viral agents...

Sabendo-se que as fezes são uma importante via de eliminação de agentes virais pelos animais portadores e que, por estarem na água, os agentes patogênicos podem se propagar mais rapidamente, objetivou-se a pesquisa de vírus em conteúdo intestinal de rãs-touro (Lithobates catesbeianus) de cinco ranários comerciais na região do Vale do Paraíba, no estado de São Paulo, pela técnica de microscopia eletrônica de transmissão. As famílias Coronaviridae, Paramixoviridae, Parvoviridae e Herpesviridae foram observadas e fotografadas. Este trabalho ressalta a importância da adoção de medidas sanitárias nas criações, além da confirmação de que a observação de fezes pela microscopia eletrônica de transmissão é uma eficiente ferramenta de diagnóstico rápido para agentes virais...

Influence of chlorhexidine and/or ethanol treatment on bond strength of an etch-and-rinse adhesive to dentin: an in vitro and in situ study.

The aim of this study was to evaluate the effect of a chlorhexidine and/or ethanol application on the bond strength of an etch-and-rinse, hydrophobic adhesive system either under in vitro aging or in situ cariogenic challenge. The dentin surface of 36 human third molars were flattened and allocated into four groups to be treated with chlorhexidine, ethanol, or chlorhexidine + ethanol or left unexposed to any solution (control) (n=9). Then, a resin composite restoration was made on the dentin surface and longitudinal sticks were obtained. Sticks from each tooth were assigned to three test conditions: stored in water in vitro for 24 hours, stored in water in vitro for 6 months, or worn in situ for 14 days. During in situ wear time, a high-cariogenic challenge condition was simulated. Specimens were tested for microtensile bond strength (µTBS). Multivariate analysis of variance and Tukey's test showed that chlorhexidine, ethanol, or chlorhexidine + ethanol did not affect the µTBS. The in vitro µTBS values were significantly lower for the specimens stored for 6 months than for those stored for 24 hours. Intermediate µTBS values were shown by the specimens worn in situ. Thus, use of chlorhexidine and/or ethanol was incapable of containing the degradation at the bond interface in the in vitro model. The in situ model was capable of reducing bond strength similarly to the in vitro/6 months model. Despite this, the in situ bond strength was still similar to that of the in vitro/24-hour model.

Clinical comparative study of the effectiveness of and tooth sensitivity to 10% and 20% carbamide peroxide home-use and 35% and 38% hydrogen peroxide in-office bleaching materials containing desensitizing agents.

The aim of this study was to compare the effectiveness of and tooth sensitivity to 10% and 20% carbamide peroxide (CP) home-use bleaching agents and 35% and 38% hydrogen peroxide (HP) in-office bleaching agents, all of which contain desensitizing agents, in a clinical trial. Four agents were evaluated: 10% CP and 20% CP (Opalescence PF 10% and Opalescence PF 20%, Ultradent, both with 0.5% potassium nitrate and 0.11% fluoride ions), 38% HP (Opalescence Boost PF, Ultradent, with 3% potassium nitrate and 1.1% fluoride ions), and 35% HP (Pola Office, SDI, with potassium nitrate). The initial screening procedure included 100 volunteers, aged 18 to 42, with no previous sensitivity or bleaching treatment and with any tooth shade. Volunteers were randomly assigned among the technique/bleaching agent groups. A run-in period was performed 1 week before the beginning of the bleaching treatment. For the home-use bleaching technique, each volunteer was instructed to dispense gel (10% CP or 20% CP) into the trays and then insert them into his or her mouth for at least two hours per night for three weeks. For the in-office bleaching technique, the bleaching agents (38% HP or 35% HP) were prepared and used following the manufacturer's instructions, with three applications performed in each session. Three sessions were carried out with an interval of seven days between each session. The participants were evaluated before, at one week, two weeks, and three weeks after the beginning of the bleaching treatment, and again one and two weeks after the bleaching treatment ended. A shade guide (Vita Classical, Vita) was used by a blinded examiner to perform shade evaluations before bleaching and two weeks after the end of bleaching. At the time of the shade evaluations, tooth sensitivity was also recorded by asking the volunteers to classify the sensitivity during bleaching treatment as absent, mild, moderate, or severe. The present study found that 13.8% of the volunteers withdrew from the study due to tooth sensitivity, and 43.2% of the participants experienced some type of sensitivity during bleaching treatment. The χ(2) test showed that there was a significant prevalence of tooth sensitivity during bleaching treatment using the home-use 20% CP agent, with 71.4% of volunteers reporting any level of tooth sensitivity (p=0.0032). A low prevalence of tooth sensitivity was observed for volunteers who used the in-office 38% HP agent (15.0%). The Wilcoxon test (p<0.05) showed that all of the bleaching treatments were effective in bleaching teeth and that there were no differences between the final color shade results among the treatments (Kruskal-Wallis, p<0.05). This study showed that 43.2% of all the volunteers experienced mild or moderate tooth sensitivity during the treatment with bleaching agents. A higher prevalence of tooth sensitivity was observed for 71.4% of the volunteers who used the 20% CP home-use bleaching agent, which may be ascribed to the peroxide concentration and/or the time/length the agent was in contact with the dental structures.