Excipient-free inhalable microparticles of Azithromycin produced by electrospray: A novel approach to direct pulmonary delivery of antibiotics

Inhalation therapy offers several advantages in respiratory disease treatment. Azithromycin is a macrolide antibiotic with poor solubility and bioavailability but with a high potential to be used to fight lung infections. The main objective of this study was to generate a new inhalable dry powder azithromycin formulation. To this end, an electrospray was used, yielding a particle size around 2.5 µm, which is considered suitable to achieve total deposition in the respiratory system. The physicochemical properties and morphology of the obtained microparticles were analysed with a battery of characterization techniques. In vitro deposition assays were evaluated after aerosolization of the powder at constant flow rate (100 L/min) and the consideration of the simulation of two different realistic breathing profiles (healthy and chronic obstructive pulmonary disease (COPD) patients) into a next generation impactor (NGI). The formulation was effective in vitro against two types of bacteria, Staphylococcus aureus and Pseudomonas aeruginosa. Finally, the particles were biocompatible, as evidenced by tests on the alveolar cell line (A549) and bronchial cell line (Calu-3). © 2021 by the authors. Licensee MDPI, Basel, Switzerland

The Arabidopsis ATK1 gene is required for spindle morphogenesis in male meiosis

The spindle plays a central role in chromosome segregation during mitosis and meiosis. In particular, various kinesins are thought to play crucial roles in spindle structure and function in both mitosis and meiosis of fungi and animals. A group of putative kinesins has been previously identified in Arabidopsis, called ATK1-ATK4 (previously known as KATA-KATD), but their in vivo functions have not been tested with genetic studies. We report here the isolation and characterization of a mutant, atk1-1, which has a defective ATK1 gene. The atk1-1 mutant was identified in a collection of Ds transposon insertion lines by its reduced fertility. Reciprocal crosses between the atk1-1 mutant and wild type showed that only male fertility was reduced, not female fertility. Molecular analyses, including revertant studies, indicated that the Ds insertion in the ATK1 gene was responsible for the fertility defect. Light microscopy revealed that, in the atk1-1 mutant, male meiosis was defective, producing an abnormal number of microspores of variable sizes. Further cytological studies indicated that meiotic chromosome segregation and spindle organization were both abnormal in the mutant. Specifically, the atk1-1 mutant male meiotic cells had spindles that were broad, unfocused and multi-axial at the poles at metaphase I, unlike the typical fusiform bipolar spindle found in the wild-type metaphase I cells. Therefore, the ATK1 gene plays a crucial role in spindle morphogenesis in male Arabidopsis meiosis

The Chicken Yolk Sac IgY Receptor, a Mammalian Mannose Receptor Family Member, Transcytoses IgY across Polarized Epithelial Cells

In mammals the transfer of passive immunity from mother to young is mediated by the MHC-related receptor FcRn, which transports maternal IgG across epithelial cell barriers. In birds, maternal IgY in egg yolk is transferred across the yolk sac to passively immunize chicks during gestation and early independent life. The chicken yolk sac IgY receptor (FcRY) is the ortholog of the mammalian phospholipase A2 receptor, a mannose receptor family member, rather than an FcRn or MHC homolog. FcRn and FcRY both exhibit ligand binding at the acidic pH of endosomes and ligand release at the slightly basic pH of blood. Here we show that FcRY expressed in polarized mammalian epithelial cells functioned in endocytosis, bidirectional transcytosis, and recycling of chicken FcY/IgY. Confocal immunofluorescence studies demonstrated that IgY binding and endocytosis occurred at acidic but not basic pH, mimicking pH-dependent uptake of IgG by FcRn. Colocalization studies showed FcRY-mediated internalization via clathrin-coated pits and transport involving early and recycling endosomes. Disruption of microtubules partially inhibited apical-to-basolateral and basolateral-to-apical transcytosis, but not recycling, suggesting the use of different trafficking machinery. Our results represent the first cell biological evidence of functional equivalence between FcRY and FcRn and provide an intriguing example of how evolution can give rise to systems in which similar biological requirements in different species are satisfied utilizing distinct protein folds

Group Approach to the Quantization of the P\"oschl-Teller dynamics

The quantum dynamics of a particle in the Modified P\"oschl-Teller potential is derived from the group $SL(2,R)$ by applying a Group Approach to Quantization (GAQ). The explicit form of the Hamiltonian as well as the ladder operators is found in the enveloping algebra of this basic symmetry group. The present algorithm provides a physical realization of the non-unitary, finite-dimensional, irreducible representations of the $SL(2,R)$ group. The non-unitarity manifests itself in that only half of the states are normalizable, in contrast with the representations of SU(2) where all the states are physical.Comment: 17 pages, LaTe

Intertwining symmetry algebras of quantum superintegrable systems on the hyperboloid

A class of quantum superintegrable Hamiltonians defined on a two-dimensional hyperboloid is considered together with a set of intertwining operators connecting them. It is shown that such intertwining operators close a su(2,1) Lie algebra and determine the Hamiltonians through the Casimir operators. By means of discrete symmetries a broader set of operators is obtained closing a so(4,2) algebra. The physical states corresponding to the discrete spectrum of bound states as well as the degeneration are characterized in terms of unitary representations of su(2,1) and so(4,2).Comment: 11 pages, 5 figure

Heat transfer in separated flows on the pressure side of turbine blades

Heat transfer in separated flows on the pressure side of a typical high lift turbine profile is numerically investigated by means of an in-house CFD code. The numerical code was first validated on attached flows in turbine blades. To obtain flow separation cases, the profile is subject to large negative incidences so that a separation bubble is obtained at the pressure side. The numerical results are compared to available experimental data for code validation. It is shown how local minima and maxima values of the heat transfer coefficient are related to the separation and reattachment points, where the velocity component perpendicular to the wall is shown to have a significant effect on the heat transfe

Cigarette smoke induces pulmonary arterial dysfunction through an imbalance in the redox status of the soluble guanylyl cyclase

Chronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking (CS), is one of the most common diseases globally. Some COPD patients also develop pulmonary hypertension (PH), a severe complication that leads to premature death. Evidence suggests reactive oxygen species (ROS) involvement in COPD and PH, especially regarding pulmonary artery smooth muscle cells (PASMC) dysfunction. However, the effects of CS-driven oxidative stress on the pulmonary vasculature are not completely understood. Herein we provide evidence on the effects of CS extract (CSE) exposure on PASMC regarding ROS production, antioxidant response and its consequences on vascular tone dysregulation. Our results indicate that CSE exposure promotes mitochondrial fission, mitochondrial membrane depolarization and increased mitochondrial superoxide levels. However, this superoxide increase did not parallel a counterbalancing antioxidant response in human pulmonary artery (PA) cells. Interestingly, the mitochondrial superoxide scavenger mitoTEMPO reduced mitochondrial fission and membrane potential depolarization caused by CSE. As we have previously shown, CSE reduces PA vasoconstriction and vasodilation. In this respect, mitoTEMPO prevented the impaired nitric oxide-mediated vasodilation, while vasoconstriction remained reduced. Finally, we observed a CSE-driven downregulation of the Cyb5R3 enzyme, which prevents soluble guanylyl cyclase oxidation in PASMC. This might explain the CSE-mediated decrease in PA vasodilation. These results provide evidence that there might be a connection between mitochondrial ROS and altered vasodilation responses in PH secondary to COPD, and strongly support the potential of antioxidant strategies specifically targeting mitochondria as a new therapy for these diseasesThe Spanish Ministerio de Ciencia e Innovacion, ´ Programa Retos en Investigacion ´ (grant number PID2019-104406RB-100) to MJC provided the financial support for the conduct of the research included in this manuscript. Garantia Juvenil program from Comunidad de Madrid contributed with the research assistant contract to M-R,

Infiltration capacity assessment of urban pavements using the LCS. Permeameter and the CP Infiltrometer.

This paper presents the Cantabrian Portable Infiltrometer (CP Infiltrometer), a specially designed device based on rainfall simulation for the assessment of the infiltration capacity of all types of urban pavements. Several pervious and impervious surfaces were tested with the LCS Permeameter, an existing infiltration test based on the use of a column of water, and the CP Infiltrometer, simulating rain intensities with return periods of 10, 50 and 500 years and 5 minutes duration. The discussion of the results indicates that the CP Infiltrometer could be used successfully to identify different levels of infiltration capacity and to assess the correct performance of pervious surfaces on which design, construction and maintenance decisions are based

Prepubertal unilateral gynecomastia: a report of two cases

Item does not contain fulltextBACKGROUND: Gynecomastia is defined as the presence of excessive breast tissue in males, which can appear unilateral or bilateral. Bilateral gynecomastia is frequently found in the neonatal period, early in puberty, and with increasing age. Prepubertal unilateral gynecomastia in the absence of endocrine abnormalities is extremely rare, with only a few cases in literature. METHODS: We report the cases of two otherwise healthy boys of 8 and 11 years old with unilateral breast masses. No abnormalities were found on ultrasonography and all endocrine parameters were within normal limits. Treatment consisted of peripheral liposuction followed by subcutaneous partial resection of the gland, conducted through an infra-areolar incision. Results : Microscopy of the subcutaneous mastectomy specimen revealed gynecomastia without signs of malignancy. Postoperative course of both patients was uncomplicated, with no signs of recurrence of breast tissue. CONCLUSIONS: Atypical presentations of gynecomastia are often not recognized, with little attention to breast development in prepubertal non-obese children. Since prepubertal gynecomastia could be a sign of possible underlying diseases, a thorough examination and further research is recommended. If there is no causal treatment, surgical resection is the therapy of first choice. Peripheral liposuction and surgical resection of the gland tissue are the mainstay of treatment. In summary, we describe two cases of prepubertal unilateral gynecomastia with a normal endocrine workup. Further research is needed to establish the pathophysiologic mechanisms of prepubertal gynecomastia, since underlying etiology in most cases remains unclear

Mechanical behavior of asphalt mixtures containing silica gels as warm additives

This paper presents the results of a study of some compounds capable of absorbing water into their structure (silica gel), as potential foaming binders. Asphalt mixtures were manufactured at different manufacturing and compaction temperatures, using four different silica gels. Static and dynamic tests were carried out to determine their behavior in asphalt mixtures. The results were compared with those obtained using hot-mix asphalt and warm-mix asphalt manufactured with zeolite. The lab results showed a similar behavior of asphalt mixtures containing either silica gel or zeolite.The research presented herein was sponsored by the Research Office of Universidad de La Frontera (DIUFRO) under the project number DI15-0089