Hertzcrowell0375
5% polyvinyl alcohol with sonication time of 60 s achieved spherical shape with particle size of 43 nm and drug entrapment of 82%. A significant bioavailability enhancement of VNP with marked prolongation of the in vivo systemic exposure of the drug and increased brain levels has also been achieved following intraperitoneal administration in Wistar rats. Thus, the optimized formulation could be regarded as a promising stealth nanocarrier that could surmount the drug pitfalls and enhance its brain delivery.The short half-life and bitter taste of carbinoxamine maleate2 (CAM) lead to poor compliance by pediatric patients who are being treated for allergic rhinitis. To address these issues, carbinoxamine-resin complexes3 (CRCs) were prepared by ion exchange and then coated with Kollicoat SR 30D. The resultant microencapsulated carbinoxamine-resin complexes4 (MCRCs) were dispersed into the medium to obtain the final suspensions. The drug loading kinetics and thermodynamics of CRCs, anti-swelling mechanism of the impregnant in MCRCs, in vitro release, and in vivo pharmacokinetics of the suspensions were systematically evaluated. The drug loading process was found to obey a first-order kinetic process that was spontaneous, entropy-reduced and exothermic, and the diffusion of CAM into the resin was the rate-limiting step. During microencapsulation, the impregnant could create a certain buffer space to control the swelling of CRCs and maintain the coating film intact. The homemade preparations had release behaviors similar to that of the reference in vitro and achieved sustained release in vivo. The low drug loading preparation had a higher relative bioavailability of 109% owing to its faster release and better dispersibility. Selleck Tanshinone I Therefore, the suspensions based on MCRCs could be successfully applied to treating allergic rhinitis in children.In this study we aimed to develop a roflumilast (R) and formoterol fumarate (F) dry powder inhaler formulation (DPI) incorporating HPβCD by spray drying and evaluated if it attenuates the inflammatory process and improves lung function in a murine model of ovalbumin induced allergic asthma. The DPI was characterized by powder X-ray diffraction, thermal analysis, scanning electron microscopy, particle size, density, specific surface area and dynamic vapor sorption analyses. In vitro deposition studies were performed using a NGI, while transepithelial permeability and in vivo effects on lung mechanics and inflammation in a model of allergic asthma were also assessed. The RF formulation was amorphous with high glass transition temperatures, comprised of wrinkled particles, had low bulk and tapped densities, high surface area, suitable particle size for pulmonary delivery and exhibited no recrystallization even at high relative humidities. MMAD were statistically similar of 4.22 ± 0.19 and 4.32 ± 0.13 µm for F and R, respectively. Fine particle fractions ( less then 5 µm) were of more than 50% of the emitted dose. The RF formulation led to reduced eosinophil infiltration and airway collagen fiber content, yielding decreased airway hyperresponsiveness. In the current asthma model, the RF formulation combination decreased inflammation and remodeling, thus improving lung mechanics.
To assess the surgical effect of single-stage superior oblique recession with intraoperative suture adjustment under topical anesthesia and sedation in terms of A-pattern correction, vertical alignment, and superior oblique overaction.
The medical records of patients who underwent superior oblique weakening (recession with adjustable suture) for superior oblique overaction from 2015 to 2018 were reviewed retrospectively. Preoperative, pre- and postadjustment, and 6-week follow-up data were assessed and compared for A pattern, primary position hypertropia, superior oblique overaction scale and objective fundus torsion.
A total of 29 patients (17-42years of age) were included. Of 51 operated eyes, 37 underwent intraoperative adjustment (further recession of 1-4mm) after superior oblique recession of 8mm. Mean decrease in primary position hyperdeviation after adjustment was 3.6
± 2.7
(range, 0
-8
); in A-pattern deviation, 5.5
±4.8
(range, 0
-16
). At 6weeks' follow-up, A pattern had either resolved completely or became clinically insignificant (<10
) in 23 of 29 patients (79%); 24 (83%) patients had hyperdeviation in primary position of ≤5
. Of the 5 patients with preoperative primary position hyperdeviation of 15
-30
, 2 had residual primary position hyperdeviation of >10
.
In our study cohort, single-stage, unilateral superior oblique tendon recession with adjustable suture under topical anesthesia and sedation was well tolerated and resulted in good postoperative outcomes at 6weeks' follow-up, effectively correcting primary position vertical deviation of <15
.
In our study cohort, single-stage, unilateral superior oblique tendon recession with adjustable suture under topical anesthesia and sedation was well tolerated and resulted in good postoperative outcomes at 6 weeks' follow-up, effectively correcting primary position vertical deviation of less then 15Δ.The isobenzofuran-1(3H)-ones (phthalides) exhibit various biological activities, including antioxidant activity on reactive oxygen species (ROS). An excess of ROS that cannot be naturally contained by cellular enzymatic systems is called redox imbalance, which damage cell membranes, proteins, and DNA, thereby possibly triggering neuronal death in several neurodegenerative diseases. Considering our ongoing efforts to find useful compounds to control redox imbalance, herein we evaluated the antioxidant activity of two phtalides (compounds 3 and 4), using primary cultures of hippocampal neurons. Spectrophotometric assays showed that compound 3 significantly reduced (p ≤ 0.05) ROS levels and lipid peroxidation compared to the control treatment, while compound 4 was unable at any of the tested concentrations. Despite their structural similarity, these compounds behave differently in the intracellular environment, which was reliably corroborated by the determination of oxidation potentials via cyclic voltammetry. It was demonstrated that compound 3 presents a lower oxidation potential. The combination of the mentioned methods allowed us to find a strong correlation between the chemical structure of compounds and their biological effects. Taking together, the results indicate that compound 3 presents desirable characteristics to act as a candidate pharmacological agent for use in the prevention and treatment of neurodegenerative diseases.With the increased use of nanomaterials and increased exposure of humans to various nanomaterials, the potential health effects of nanomaterials cannot be ignored. The hepatotoxicity of cobalt nanoparticles (Nano-Co) is largely unknown and the underlying mechanisms remain obscure. The purpose of this study was to exam the hepatotoxicity induced by Nano-Co and its potential mechanisms. Our results showed that exposure of human fetal hepatocytes L02 to Nano-Co caused a dose- and a time-dependent cytotoxicity. Besides the generation of reactive oxygen species (ROS) and mitochondrial reactive oxygen species (mtROS), exposure to Nano-Co also caused activation of NOD-like receptor protein 3 (NLRP3) inflammasome in hepatocytes. After silencing NLRP3, one component of NLRP3 inflammasome, expression by siRNA strategy, we found that upregulation of NLRP3-related proteins was abolished in hepatocytes exposed to Nano-Co. Using antioxidants to scavenge ROS and mtROS, we demonstrated that Nano-Co-induced mtROS generation was related to Nano-Co-induced NLRP3 inflammasome activation. Our findings demonstrated that Nano-Co exposure may promote intracellular oxidative stress damage, and mtROS may mediate the activation of NLRP3 inflammasome in hepatocytes exposed to Nano-Co, suggesting an important role of ROS/NLRP3 pathway in Nano-Co-induced hepatotoxicity. These results provide scientific insights into the hepatotoxicity of Nano-Co and a basis for the prevention and treatment of Nano-Co-induced cytotoxicity.In vitro chemical risk assessment using human cells is emerging as an alternative to in vivo animal testing with reduced costs, fewer animal welfare concerns, and the possibility of greater human health relevance. In vitro inhalation toxicity testing of volatile compounds poses particular challenges. Here we report our efforts to establish a testing protocol in our own lab using the EpiAirway bronchial epithelium cell culture model and the Vitrocell 12/12 system for air-liquid interface (ALI) exposures. For purposes of method development, we used methyl iodide (MeI) as a test compound. We examined viability, cytotoxicity, and epithelial integrity responses. Dose-dependent, reproducible responses were observed with all assays. EpiAirway and BEAS-2B cytotoxicity responses to acute exposure were roughly similar, but EpiAirway was more resistant than BEAS-2B by the viability measurement, suggesting a proliferative response at low MeI concentrations. If wells were sealed to prevent evaporation, in-solution MeI concentration-response could be used to predict the response to MeI vapor within 2-fold by converting from the media- to the air-concentration at equilibrium using the bloodair partition coefficient for MeI. The long-term stability of EpiAirway cultures enabled repeated exposures over a 5-d period, which produced responses at lower concentrations than did acute exposure.CuO nanoparticles (CuO-NPs) toxicity in organisms is contributed mainly through the copper uptake by both the ionic and nanoparticle form. However, the relative uptake ratio and bioavailability of the two different forms is not well known due to a lack of sensitive and effective assessment systems. We developed a series of both copper resistant and hyper sensitive Saccharomyces cerevisiae mutants to investigate and compare the effects of CuO-NPs and dissolved copper (CuCl2), on the eukaryote with the purpose of quantitating the relative contributions of nanoparticles and dissolved species for Cu uptake. We observed the toxicity of 10 mM CuO-NPs for copper sensitive strains is equal to that of 0.5 mM CuCl2 and the main toxic effect is most likely generated from oxidative stress through reactive oxygen species (ROS) production. About 95% CuO-NPs exist in nanoparticle form under neutral environmental conditions. Assessing the cellular metal content of wild type and copper transporter 1(CTR1) knock out cells showed that endocytosis is the major absorption style for CuO-NPs. This study also found a similar toxicity of Ag for both 10 mM Ag-NPs and 0.2 mM AgNO3 in the copper super sensitive strains. Our study revealed the absorption mechanism of soluble metal based nanomaterials CuO-NPs and Ag-NPs as well as provided a sensitive and delicate system to precisely evaluate the toxicity and stability of nanoparticles.Lung cancer is the most common cause of cancer-related death worldwide. The occurrence of multidrug resistance (MDR) affects the therapeutic efficacy of chemotherapeutics. Therefore, to develop new anticarcinogen which can overcome MDR is urgent. Here, the novel microtubule inhibitor 5-(4-ethoxyphenyl)-1-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazol-3-amine (YAN) exhibited strong cytotoxicity towards A549 and MDR-phenotype A549/Taxol cells. We demonstrated that YAN was a poor substrate of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) which were over-expressed in A549/Taxol cells, and YAN inhibited their expression and function. Moreover, YAN arrested cells at mitosis phase by inhibiting microtubule polymerization. Further, YAN induced caspase-dependent apoptosis in A549 cells via mitochondria-mediated intrinsic pathway. In contrast, the multinucleation of A549/Taxol cells after YAN-treatment indicated the occurrence of mitotic catastrophe, and the subsequent apoptosis was mediated by apoptosis-inducing factor (AIF) nuclear translocation instead of p53- and caspase-dependent manner.
