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Modern Operative Approaches for Nasal Septal Perforations: Operations as well as Remedy.
It has been proposed that changes in microbiota due to nonsteroidal anti-inflammatory drugs (NSAIDs) alter the composition of bile, and elevation of hydrophobic secondary bile acids contributes to small intestinal damage. However, little is known about the effect of NSAIDs on small intestinal bile acids, and whether bile alterations correlate with mucosal injury and dysbiosis. Here we determined the ileal bile acid metabolome and microbiota 24, 48 and 72 h after indomethacin treatment, and their correlation with each other and with tissue damage in rats. In parallel with the development of inflammation, indomethacin increased the ileal proportion of glycine and taurine conjugated bile acids, but not bile hydrophobicity. Firmicutes decreased with time, whereas Gammaproteobacteria increased first, but declined later and were partially replaced by Bilophila, Bacteroides and Fusobacterium. Mucosal injury correlated negatively with unconjugated bile acids and Gram-positive bacteria, and positively with taurine conjugates and some Gram-negative taxa. Strong positive correlation was found between Lactobacillaceae, Ruminococcaceae, Clostridiaceae and unconjugated bile acids. Indomethacin-induced dysbiosis was not likely due to direct antibacterial effects or alterations in luminal pH. Here we provide the first detailed characterization of indomethacin-induced time-dependent alterations in small intestinal bile acid composition, and their associations with mucosal injury and dysbiosis. Our results suggest that increased bile hydrophobicity is not likely to contribute to indomethacin-induced small intestinal damage.Previously our laboratory first reported that dropping of freeze-dried monoclonal antibody (mAb) formulations could cause protein degradation and aggregation (J Pharm Sci, 2021, 1625). In this manuscript, we evaluated effects of secondary package on stability of several freeze-dried biopharmaceutical formulations during dropping. The degradation of mAb-Y during dropping with different secondary packages was determined by the sensitive particle analyzing techniques micro-flow imaging (MFI) and dynamic light scattering (DLS). Electron paramagnetic resonance (EPR) was used to detect free radicals after repeated dropping in different secondary packages. The amount of free radicals and SbVPs was correlated to the sample temperature as well as the secondary package during dropping. Our observations suggest that secondary packaging has significant effect on freeze-dried biopharmaceutical stability during dropping and therefore should be thoroughly screened and optimized to assure high product quality even for the presumed highly stable freeze-dried biopharmaceuticals.Acid-reducing agents (ARAs) are the most commonly used medicines to treat patients with gastric acid-related disorders. ARA administration results in an elevation of intragastric pH and eases symptoms such as acid reflux. However, this effect could also lead to a reduction in the absorption of some co-administered oral medications (i.e. weakly basic drugs) by decreasing their gastric solubility. This in turn can result in a significant reduction of the efficacy of the co-administered oral medications. In order to address this problem, substantial efforts in translational modeling and the development of predictive in-vitro assays to better forecast the effect of ARA on oral absorption are conducted in the pharmaceutical industry. Despite these efforts, it remains challenging to predict the impact of ARAs on co-administered drugs. In this study, we evaluated the utility of Triskelion's Gastro-Intestinal Model (Tiny-TIM) in predicting ARA effect on twelve model drugs whose in-vivo data are available. The Tiny-TIM prediction of the ARA effect matched the observed effect of ARA co-administration in humans for the 12 model compounds. In summary, Tiny-TIM is a very reliable and promising GI model to successfully predict the nature of DDI when ARAs are co-administered with the drug of interest.In the present study, we aimed to formulate, optimize, and characterize azithromycin chitosan coated niosomes (AZM-CTS-NSM) as a novel colloidal system that increases precorneal residence period, eye permeation, and bioavailability. selleck kinase inhibitor AZM-NSM was formulated via a modified thin-film hydration strategy and then coated with CTS. We assessed the influence of the cholesterol surfactant molar ratio, CTS concentration, and surfactant type on particle diameter, entrapment, zeta potential, and NSM adhesion force to the corneal mucosal membrane and employed a central composite design (CCD). The resulting optimized AZM-CTS-NSM has a mean diameter of 376 nm, entrapment of 74.2%, surface charge of 32.1 mV, and mucoadhesion force of 3114 dyne/cm2. The optimized AZM-CTS-NSM demonstrated a prolonged in vitro release behavior. When compared with commercial eye drops, the optimized AZM-CTS-NSM produced a 2.61-fold increase in the apparent permeability coefficient, significantly improving corneal permeability. Additionally, ocular irritation was assessed, with no major irritant effects found to be induced by the formulated NSM. Compared with AZM commercial drops, the optimized AZM-CTS-NSM revealed ˃ 3-fold increase in AZM concentration in the rabbit eyes. Collectively, these findings indicate that CTS-NSM is a potentially valuable ocular nanocarrier that could augment the efficacy of AZM.Dioxopromethazine (DPZ) is a popular phenothiazine antihistamine that is widely used as a racemic drug in clinical to cure respiratory illness. In our work, a reliable, specific, and rapid enantioselective HPLC-MS/MS method has been established and fully validated for the quantification of R- and S-DPZ in rat plasma. After plasma alkalization (with 1 M Na2CO3), DPZ enantiomers and diphenhydramine (IS) were extracted using ethyl acetate. Completely separation of R- and S-DPZ (Rs = 2.8) within 12 min was implemented on Chiralpak AGP column (100 × 4.0 mm i.d., 5 μm) employing ammonium acetate (10 mM; pH 4.5) - methanol (9010, v/v) as mobile phase. Themultiple reaction monitoring (MRM) mode was used for the detection of DPZ enantiomers and IS. The transitions of m/z 317.2 → 86.1 and 256.2 → 167.1 werechosen for monitoring DPZ enantiomers and IS, respectively. Good linearity (r2 > 0.995) was achieved for each DPZ enantiomer over the linear ranges of 1.00 - 80.00 ng/mL, with the lower limit of quantitation (LLOQ) of 1.
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