Robbtravis8851

The application of 3D printing technology for generating tablets is attracting the attention of the pharmaceutical industry following approval of a 3D printed tablet (Spritam) by the US Food and Drug Administration. Here we focused on hollow-type suppository formulations typically prepared as suppository shells by pharmacists in hospitals. We used a fused deposition modeling-type 3D printer and polyvinyl alcohol filament as a water soluble material to print suppository shells with various thicknesses and different inner structures by changing the printing conditions for the 3D designed objects. The hardness of the suppository shell was dependent on the thickness and designed inner structure. An active pharmaceutical ingredient ionic liquid, a novel type of liquid drug formulation, was loaded in the suppository shells. The drug dissolution profile of the suppository formulations differed depending on the type of suppository shell. Composite suppository formulations (two drugs in separate compartments in the suppository shell) were prepared as a model tailored medicine for pediatric patients. Our findings suggest that 3D printing technology is applicable to the preparation of hollow-type suppository formulations and may be compatible with on-site hospital production.Survivin stands out as one of the most specific cancer targets discovered to date. Although single inhibition, e.g. through small interfering RNA (siRNA), has shown modest results in clinical trials, its combination with drugs holds promise to sensitize cancer cells to chemotherapeutics. selleck compound In this study, we propose a sequential treatment of siRNA survivin followed by chemotherapy. Firstly, we demonstrated that siRNA-loaded switchable lipid nanoparticles (siLNP) silence survivin in a panel of cancer cell lines. Subsequently, we selected retinoblastoma (RB) as our model to screen four chemotherapeutic agents carboplatin, topotecan, melphalan or teniposide. The effect of drugs on survivin expression and caspase-3 was investigated by RT-qPCR. The best drug combination was selected measuring the viability, survivin expression and the selectivity of the treatment. Our stepwise method revealed that siRNA delivery by switchable LNP sensitized Y79, but not the healthy APRE-19 cell line, to carboplatin and melphalan cytotoxicity. This ability was validated on primary human RB cells. Finally, the distinct behavior of the drugs demonstrated that a diligent screening of drugs should be envisioned when looking for synergy with survivin. Our sequential approach highlighted carboplatin and melphalan as agents to be investigated in future survivin-associated in vivo testing to tackle RB.Mechanical insult induced by intraocular pressure (IOP) is likely a driving force in the disease process of glaucoma. This study aimed to evaluate regional displacements in human optic nerve head (ONH) and peripapillary tissue (PPT) in response to acute IOP elevations, and their correlations with morphological characteristics of the posterior eye. Cross-sectional (2D) images of the ONH and PPT in 14 globes of 14 human donors were acquired with high-frequency ultrasound during whole globe inflation from 5 to 30 mm Hg. High-frequency ultrasound has a spatial resolution of tens of micrometers and is capable of imaging through the ONH and PPT thickness. Tissue displacements were calculated using a correlation-based speckle tracking algorithm for a dense matrix of kernels covering the 2D imaging plane. The ONH was manually segmented in the ultrasound B-mode images acquired at 5 mmHg based on echogenicity. The lamina cribrosa (LC) boundaries were visible in eight of the fourteen eyes and the LC region was segmentedLC may play a major role in preventing excessive posterior displacement of ONH during acute IOP elevations.Trypanosoma cruzi has a complex life cycle involving four life stages the replicative epimastigotes and metacyclic trypomastigotes in the invertebrate host digestive tract, and intracellular amastigotes and bloodstream trypomastigotes in the mammalian host. Trypomastigotes can invade any nucleated cell, including macrophages, which produce ROS that enhance intracellular infection. However, how ROS modulate T. cruzi infection in the mammalian cell remains unclear. Therefore, the present work aimed to investigate the role of ROS during the stimulation of amastigogenesis in vitro. Our results showed that H2O2 improves the differentiation process in vitro and that it was impaired by Peg-Catalase. However, the antioxidants GSH and NAC had no influence on induced amastigogenesis, which suggests the specificity of H2O2 to increase intracellular differentiation. Amastigogenesis physiologically occurs in low pH, thus we investigated whether parasites are able to produce ROS during amastigogenesis. Interestingly, after 60 min of differentiation induction in vitro, we observed an increase in H2O2 production, which was inhibited by the mitochondrial-targeted antioxidant, mitoTEMPO and Cyclosporine A (a mitochondrial permeability transition pore -mPTP- inhibitor), suggesting mitochondrion as a H2O2 source. Indeed, quantitative real time (qPCR) showed an increase of the mitochondrial superoxide dismutase (FeSODA) gene expression after 60 min of induced amastigogenesis, reinforcing the hypothesis of mitochondrial ROS induction during intracellular differentiation of T. cruzi. The reduction of cellular respiration and the decreased ΔΨm observed during amastigogenesis can explain the increased mitochondrial ROS through mPTP opening. In conclusion, our results suggest that H2O2 is involved in the amastigogenesis of T. cruzi.The predatory giant ant Dinoponera quadriceps is one of the largest venomous ants on Earth. The venom of D. quadriceps comprises a rich blend of bioactive peptides that includes structures related to at least five classes of antimicrobial peptides. In the present study, two representative synthetic peptides, sDq-2562 and sDq-3162, belonging to the ponericin-like dinoponeratoxin family, were evaluated for their microbicide activity against antibiotic-resistant bacteria. The most effective peptide, the 28-residue sDq-3162 displayed a significant bacteriostatic and bactericidal effect with minimal inhibitory concentrations (MICs) between 5 μM and 10 μM (15.6 μg mL-1 and 31.2 μg mL-1), according to the strain of drug-resistant bacteria tested. In combination with conventional antibiotics, sDq-3162 displayed in vitro synergistic effects, reducing the MICs of antibiotics for more than 2-log against clinical isolates of carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa, with low cytotoxicity to human erythrocytes, in vitro.