Particle inhalability of a standing mannequin with large airways in a ventilated room.

This study presents a series of numerical simulations for airflow field and particle dispersion and deposition around a mannequin inside a ventilated room. A 3-D airway system of a volunteer subject with a large respiratory system was reconstructed from the nostril inlet to the end of the tracheobronchial tree 4th generation and was integrated into a standing mannequin at the center of a room. The room ventilation system supplied air through a diffuser and expelled air via a damper in three modes. The airflow field was first evaluated by solving the governing equations and the k-ω SST transitional turbulence model using the Ansys-Fluent software. Then spherical particles with various diameters were released into the room, and their trajectories were evaluated using the Lagrangian approach. Aspiration fraction and particle deposition for inhalation flow rates of 15 and 30 L/min were analyzed using a modified discrete random walk (DRW) stochastic model using a user-defined function (UDF) coupled to the Ansys-Fluent discrete phase model. For the first ventilation mode, a recirculation flow region formed behind the mannequin that led the airflow streamlines to the breathing zone. A recirculation flow formed in front of the face for the second ventilation mode that led the airflow streamlines out of the mannequin breathing zone. For the third mode, however, there was no strong recirculation flow zone around the mannequin. Simulation results showed that the aspiration fraction in the first ventilation mode was higher than the other modes. In addition, the regional deposition rates and deposition patterns of particles inside the respiratory system were presented for each region. Accordingly, most large particles were trapped in the nasal passage; however, some large particles penetrated deeper into the airway due to the large airway size. For the higher breathing rate, the percentage of large escaped particles from the lobe branches dropped by a factor of 7 compared to the lower breathing rate.

α-Cyperone of Cyperus rotundus is an effective candidate for reduction of inflammation by destabilization of microtubule fibers in brain.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyperus rotundus L. (Cyperaceae), commonly known as purple nutsedge or nut grass is one of the most invasive and endemic weeds in tropical, subtropical and temperate regions. This plant has been extensively used in traditional medicine for anti-arthritic, antidiarrheal and antiplatelet properties as well as treatment for several CNS disorders such as epilepsy, depression and inflammatory disorders. Inflammation is evidently occurring in pathologically susceptible regions of the Alzheimer's disease (AD) brain as well as other disorders. Many cellular processes are responsible in chronic inflammation. Microtubule-based inflammatory cell chemotaxis is a well-recognized process that influences production of cytokines and phagocytosis. The effect of α-Cyperone, one of main ingredients of Cyperus rotundus on microtubule assembly and dynamics has not been examined and is the purpose of this investigation. MATERIALS AND METHODS: Microtubules and tubulin were extracted in order to explore their interaction with α-Cyperone by utilization of turbidimetric examinations, intrinsic fluorescence and circular dichroism spectroscopy (CD) studies. The molecular docking analysis was executed in order to facilitate a more detail and stronger evidence of this interaction. The BINding ANAlyzer (BINANA) algorithm was used to evaluate and further substantiate the binding site of α-Cyperone. RESULTS: It was demonstrated that α-Cyperone had a pronounced influence on the tubulin structure, decreased polymerization rate and reduced concentration of polymerized tubulin in vitro. The CD deconvolution analysis concluded that significant conformational changes occurred, demonstrated by a drastic increase in content of ß-strands upon binding of α-Cyperone. The fluorescence spectroscopy revealed that a static type of quenching mechanism is responsible for binding of α-Cyperone to tubulin. Upon characterization of various biophysical parameters, it was further deduced that ligand binding was spontaneous and a single site of binding was confirmed. Transmission electron microscopy revealed that upon binding of α-Cyperone to microtubule the number and complexity of fibers were noticeably decreased. The computational analysis of docking suggested that α-Cyperone binds preferably to ß-tubulin at a distinct location with close proximity to the GTP binding and hydrolysis site. The ligand interaction with ß-tubulin is mostly hydrophobic and occurs at amino acid residues that are exclusively on random coil. The BINANA 1.2.0 algorithm which counts and tallies close molecular interaction by performing defined set of simulations revealed that amino acid residues Arg 48 and Val 62 have registered the highest scores and are possibly crucial in ligand-protein interaction. CONCLUSION: α-Cyperone binds and interacts with tubulin and is capable of distinctly destabilizing microtubule polymerization. The effect of this interaction could result in reduction of inflammation which would be highly beneficial for treatment of inflammatory diseases such as AD.