ABSTRACT
Background: Acute sinusitis is not an uncommon disease that manifests with inflammation of the mucosal lining of the paranasal sinuses. It has varied etiologies including viral, bacterial, fungal, and allergic. Anatomical variations, trauma, auto-immunity, diabetes mellitus, and dental procedures are predisposing factors. With the wide variation in the etiological factors, the management could be tricky. This study is quite relevant with the advent of the relentlessly persisting COVID-19 pandemic which affects the upper respiratory tract as well. Method(s): This is a descriptive hospital-based prospective study conducted at the Khartoum ENT Teaching Hospital, Ibnsina Teaching Hospital, Omdurman Military Hospital, and Omdurman Teaching Hospital in Khartoum State in the period from March 2020 to February 2021. The study included all patients 18 years and older diagnosed with acute sinusitis. The data was collected by a well-structured questionnaire designed to meet the objectives of the study and analyzed using SPSS 20. Any COVID-19 suspect is excluded from the study. Result(s): The total number of patients was 109;of them, 59 (54.1%) were females and 50 (45.9%) were males, and the female to male ratio was 1.18:1. One hundred seven (98.2%) patients received medical treatment and two patients (1.8%) did take the medications. Eighty-one patients (74.3%) were cured with medical treatment and only 28 patients (25.7%) needed surgical intervention. The age group from 25 to 40 years old was the most affected, accounting for 68 patients (62.4%), and the above 60 years old (3.7%) was the least affected group. Conclusion(s): Acute sinusitis is not an uncommon disease, if addressed properly and timely is medically treatable in most cases apart from complicated cases. This study shows that the active working ages (25-40) were the most affected. Few patients needed surgery (FESS). Negligence could result in complications. Diseases like COVID-19 affect the upper respiratory tract, and there is a similarity in symptoms, and in the advent of the COVID-19 pandemic nowadays, differentiation is of paramount importance.Copyright © 2022, The Author(s).
ABSTRACT
Rationale: Cell-penetrating peptides are able to cross membranes and deliver cargoes in a functional form. Our prior work identified a 12-amino acid, cardiac targeting peptide (APWHLSSQYSRT). Studies into its mechanism of transduction led to the identification of two lung targeting peptides (LTPs), S7A and R11A. Here we report on a) the comparative lung uptake of S7A versus R11A, b) complete biodistribution of R11A, c) show that cyclic versions are -100-fold more efficient than linear counterparts, d) uptake is via a non-endocytic pathway, and e) cyclic R11A's (cR11A) ability to deliver siRNA targeting structural proteins of SARS-CoV-2 and act as an anti-viral. Methods: Linear LTPs were synthesized with N-terminal labeled with Cyanine 5.5 (Cy5.5). Cyclic versions were synthesized with lysine added to the N-terminus, cyclized through a peptide bond, with a side NH-group labeled with Cy5.5. cR11A was conjugated to siRNA duplexes via a DTME linker. Wild-type, CD1 mice, were injected with S7A or R11A at 10, 5, and 1mg/Kg, peptides allowed to circulate for 15mins, mice euthanized, lung along with multiple other organs dissected and imaged using In Vivo Imaging Systems (IVIS, Perkin-Elmer) followed by confocal microscopy. CD1 mice were injected with R11A, 5mg/Kg, and euthanized at different time intervals for biodistribution studies. Endocytosis studies were done using serum-starved human bronchial epithelial cells (HBEC) incubated with fluorescently labeled transferrin and LTP-S7A or LTP- R11A. Lastly, anti-viral activity was tested in HBECs pre-treated with cR11A-siRNA followed by viral infection. Results: Mice injected with LTP-S7A or LTP-R11A showed robust uptake of the peptides by lung tissue, with R11A showing an increasingly favorable lung:liver ratio with decreasing dose. Lung uptake of R11A peaked at 120mins with complete dissipation of fluorescence by 24 hours. In Vitro studies in HBECs showed no co-localization of transferrin with LTPs, ruling out endocytosis as a mechanism of uptake. Comparison of linear versus cyclic peptides using FACS showed cyclic peptides had -100-fold increased transduction efficiency over their linear counterparts. cR11A conjugated to ant-spike, and anti-envelop proteins showed an anti-viral effect with EC90 of 0.6uM and 1.0μM, respectively. Conclusions: We have identified two novel lung-targeting peptides capable of acting as delivery vectors. Peak uptake of R11A occurred at 120mins. Furthermore, this uptake was not via endocytosis, and cyclic versions were -100-fold more efficiently taken up. Lastly, as proof of concept, we show cR11A acts as a vector and delivers siRNA to HBECs in a functional form, and act as anti-virals.