Pharmacists' Attitudes Towards Long-Term Use of Nasal Decongestants: A Cross-Sectional Study.

Background: Rhinitis medicamentosa is a nonallergic inflammation of the nasal mucosa caused by topical decongestants overuse. It mainly affects young and middle-aged adults. Therefore, the aim of this study was to investigate the attitudes of pharmacists regarding the utilization of over-the-counter intranasal decongestants. Methods: An online cross-sectional study was conducted from November 2021 to January 2022. The target population of the study included pharmacists who work in community pharmacies in Saudi Arabia. Binary logistic regression analysis was used to identify predictors of having positive attitude towards controlling the use of decongestant. Results: A total of 220 participants were included in this study. Around 15.0% of them reported that ND come with a physician prescription. The majority of the participants (87.3%) reported that the less than 5 days is the maximum safe duration for the use of NDs. Overall, the study participants demonstrated moderately positive attitude towards controlling the use of decongestant with a mean attitude score of 2.5 (standard deviation: 1.2) out of 5; which represents 50.0% of the maximum score. Binary logistic regression analysis identified that pharmacists aged 31-40 years were two-folds more likely to have positive attitude towards controlling the use of decongestant compared to others (p<0.05). Around 45.9% of them reported that they recommend other over-the-counter treatments like nasal irrigation, nasal steroids, or antihistamine if they see a patient with RM asking for ND with or without prescription. Conclusion: The majority of pharmacists in Saudi Arabia demonstrated sufficient awareness and understanding on the adverse effects associated with the excessive use of NDs. Rhinitis medicamentosa can be avoided by appropriate measures, highlighting the importance of raising awareness about the excessive use of decongestants among healthcare professionals and patients alike.

In-silico and in-vitro functional validation of imidazole derivatives as potential sirtuin inhibitor.

Introduction: Epigenetic enzymes can interact with a wide range of genes that actively participate in the progression or repression of a diseased condition, as they are involved in maintaining cellular homeostasis. Sirtuins are a family of Class III epigenetic modifying enzymes that regulate cellular processes by removing acetyl groups from proteins. They rely on NAD+ as a coenzyme in contrast to classical histone deacetylases (HDACs) (Class I, II, and IV) that depend on Zn+ for their activation, linking their function to cellular energy levels. There are seven mammalian sirtuin isoforms (Sirt1-7), each located in different subcellular compartments. Sirtuins have emerged as a promising target, given that inhibitors of natural and synthetic sources are highly warranted. Imidazole derivatives are often investigated as sirtuin regulators due to their ability to interact with the binding site and modulate their activity. Imidazole bestows many possible substitutions on its ring and neighboring atoms to design and synthesize derivatives with specific target selectivity and improved pharmacokinetic properties, optimizing drug development. Materials and methods: Ligand preparation, protein preparation, molecular docking, molecular dynamics, density function theory (DFT) analysis, and absorption, distribution, metabolism, and excretion (ADME) analysis were performed to understand the interacting potential and effective stability of the ligand with the protein. RT-PCR and Western blot analyses were performed to understand the impact of ligands on the gene and protein expression of Class III HDAC enzymes. Results and discussion: We evaluated the sirtuin inhibition activity of our in-house compound comprised of imidazole derivatives by docking the molecules with the protein data bank. ADME properties of all the compounds used in the study were evaluated, and it was found that all fall within the favorable range of being a potential drug. The molecule with the highest docking score was analyzed using DFT, and the specific compound was used to treat the non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H460. The gene and protein expression data support the in-silico finding that the compound Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate has an inhibitory effect on nuclear sirtuins. In conclusion, targeting sirtuins is an emerging strategy to combat carcinogenesis. In this study, we establish that Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate possesses a strong inhibitory effect on nuclear sirtuins in NSCLC cell lines.

Ameliorative inhibition of sirtuin 6 by imidazole derivative triggers oxidative stress-mediated apoptosis associated with Nrf2/Keap1 signaling in non-small cell lung cancer cell lines.

Background: Redox homeostasis is the vital regulatory system with respect to antioxidative response and detoxification. The imbalance of redox homeostasis causes oxidative stress. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, also called Nfe2l2)/Kelchlike ECH-associated protein 1 (Keap1) signaling is the major regulator of redox homeostasis. Nrf2/Keap1 signaling is reported to be involved in cancer cell growth and survival. A high level of Nrf2 in cancers is associated with poor prognosis, resistance to therapeutics, and rapid proliferation, framing Nrf2 as an interesting target in cancer biology. Sirtuins (SIRT1-7) are class III histone deacetylases with NAD + dependent deacetylase activity that have a remarkable impact on antioxidant and redox signaling (ARS) linked with Nrf2 deacetylation thereby increasing its transcription by epigenetic modifications which has been identified as a crucial event in cancer progression under the influence of oxidative stress in various transformed cells. SIRT6 plays an important role in the cytoprotective effect of multiple diseases, including cancer. This study aimed to inhibit SIRT6 using an imidazole derivative, Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate, to assess its impact on Nrf2/Keap1 signaling in A549 and NCI-H460 cell lines. Method: Half maximal inhibitory concentration (IC50) of Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate was fixed by cell viability assay. The changes in the gene expression of important regulators involved in this study were examined using quantitative real-time PCR (qRT-PCR) and protein expression changes were confirmed by Western blotting. The changes in the antioxidant molecules are determined by biochemical assays. Further, morphological studies were performed to observe the generation of reactive oxygen species, mitochondrial damage, and apoptosis. Results: We inhibited SIRT6 using Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate and demonstrated that SIRT6 inhibition impacts the modulation of antioxidant and redox signaling. The level of antioxidant enzymes and percentage of reactive oxygen species scavenging activity were depleted. The morphological studies showed ROS generation, mitochondrial damage, nuclear damage, and apoptosis. The molecular examination of apoptotic factors confirmed apoptotic cell death. Further, molecular studies confirmed the changes in Nrf2 and Keap1 expression during SIRT6 inhibition. Conclusion: The overall study suggests that SIRT6 inhibition by imidazole derivative disrupts Nrf2/Keap1 signaling leading to oxidative stress and apoptosis induction.

Incidental detection of paranasal sinuses abnormalities on CT imaging of the head in Saudi adult population.

The paranasal sinuses are hollowed, air-filled cavities surrounding the nasal cavity. Many pathological processes affect the sinuses, but inflammatory conditions are the commonest, even in asymptomatic patients who undergo head imaging for other indications showing one or more abnormalities of the sinuses. Our research aims to determine the prevalence of incidental paranasal sinuses abnormalities seen among patients who undergo head CT scanning. In addition, it provides baseline information for further investigations required. The study was designed to evaluate all patients who underwent head CT scanning for any reason unrelated to paranasal sinuses abnormalities. 1849 cases were selected and retrospectively analyzed from the elective and emergency CT in the last nine months, from August 2020 to April 2021. In order to meet the inclusion criteria, indications for imaging must not be sinus-related. The study was conducted on 1849 cases who had undergone head CT scans for pathology, 1204 (65%) were male and 645 (35%) were female. Abnormalities of the sinuses were found in about 617 (33%) of all patients, with a higher rate in males (22.23%) than females (11.14%). In addition, these abnormalities were found in younger patients at a higher rate than in middle and old ages 19.74%, 7.19%, and 6.44%, respectively. Our findings revealed that the prevalence of paranasal sinuses abnormalities in asymptomatic Saudi patients was high (33%). Most of the affected sinuses were the maxillary. The male patients were more affected than females in all findings.