Eczacılık Fakültesi / Faculty of Pharmacy
Permanent URI for this collectionhttps://hdl.handle.net/11727/5700
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Item An Essential Problem in Antimicrobial Stewardship: Multi-Drug-Resistant Gram-Negative Bacterial Infection in the Intensive Care Unit(Başkent Üniversitesi, 2024-02-01) Pehlivanli, Aysel; Ozgun, Cigdem; Yuksel, Didem; Solmaz, Firdevs Gonca Sasal; Ozcelikay, Arif Tanju; Unal, Mustafa NecmettinItem The Impact of Clinical Pharmacist in Geriatric Drug-Related Problems: A Scoping Review(Başkent Üniversitesi, 2024-02-01) Ediz, Cigdem; Bicer, Asim Emre; Pehlivanli, Aysel; Basgut, Bilgen; Ozcelikay, Arif TanjuItem Electrospun Hesperidin Nanofibers Induce A Cytoprotective Effect On Sodium-Fluoride Induced Oxidative Stress In Vitro(JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, 2024-03-08) Birer, Mehmet; Kara, Adnan Altug; Yurdakok-Dikmen, Begum; Uyar, Recep; Aralan, Gizem; Birer, Yagmur Turgut; Filazi, Ayhan; Acartuerk, FusunAs a bioactive flavonoid in Citrus seeds, hesperidin exerts significant antioxidant, free radical scavenging, and anticancer activity with limited bioavailability. To enhance the stability and improve the bioactive potential of hesperidin, an electrospun nanofiber formulation was developed. Electrospinning solution was characterized by surface tension, viscosity, and conductivity measurements, and these values were found to be 25.18 +/- 0.04 mN/ m 145 +/- 2 cPs and 9.0 +/- 0.4 mu S/cm, respectively. Electrospun hesperidin nanofiber was tested in a coincubation with the cytotoxic agent sodium fluoride (NaF) in Caco-2 cells. Inhibitory concentration-50 (IC50) values of hesperidin nanofiber in Caco-2 cells alone were as low as 30 mu M, indicating its potential anticancer effect, while coincubation with 10 and 20 mu M of hesperidin nanofibers was found to alleviate the cytotoxic effect induced by NaF at 2.1, 1.05 and 0.525 mM concentrations. This effect was in accordance with cellular antioxidant mechanisms; where malondialdehyde (MDA) levels at 10 mu M hesperidin nanofiber were found to be decreased by 55.60% in the thiobarbituric acid reactive substances (TBARS) assay, and the mRNA expression of Thioredoxin1 (TRX1) and Superoxide dismutase-1 (SOD1) were decreased in qPCR. The results revealed that electrospun nanofiber of hesperidin was developed for the first time with useful implications against cellular toxicity by alleviating the cellular antioxidant defense mechanisms, including MDA, SOD1, and TRX1.Item Cerliponase Alfa Decreases Aβ Load And Alters Autophagy- Related Pathways In Mouse Hippocampal Neurons Exposed To Faβ1-42(LIFE SCIENCES, 2024-11-15) Kose, Selma; Cinar, Elif; Akyel, Hilal; Cakir-Aktas, Canan; Tel, Banu Cahide; Karatas, Hulya; Kelicen-Ugur, PelinExtracellular aggregation of amyloid-beta (A beta) in the brain plays a central role in the onset and progression of Alzheimer's disease (AD). Moreover, intraneuronal accumulation of A beta via oligomer internalization might play an important role in the progression of AD. Deficient autophagy, which is a lysosomal degradation process, occurs during the early stages of AD. Tripeptidyl peptidase-1 (TPP1) functions as a lysosomal enzyme, and TPP1 gene mutations are associated with type 2 late infantile neuronal ceroid lipofuscinosis (LINCL). Nevertheless, there is little information about the role of TPP1 in the pathogenesis of AD; therefore, the present study aimed to measure the decrease in intraneuronal A beta accumulation by a recombinant analog of the TPP1 enzyme, cerliponase alfa (CER) (Brineura (R)), and to determine whether autophagy pathways play a role in this decrease. In this study, endogenous A beta accumulation was induced by fA beta(1-42) (a toxic fragment of full-length A beta) exposure, and mouse hippocampal neuronal cells (HT-22) were treated with CER (human recombinant rhTPP1 1 mg mL-1). Soluble A beta, TPP1, and the proteins involved in autophagy, including mammalian target of rapamycin (p-mTOR/ mTOR), p62/sequestosome-1 (p62/SQSTM1), and microtubule-associated protein 1 A/1B-light chain 3 (LC3), were evaluated using western blotting. The sirtuin-1, beclin-1, and Atg5 genes were also studied using RT-PCR. A beta and TPP1 localizations were observed via immunocytochemistry. CER reduced the A beta load in HT-22 cells by inducing TPP1 expression and converting pro-TPP1 into the mature form. Furthermore, exposure to CER and fA beta(1-42) induced the autophagy-regulatory/related pathways in HT-22 cells and exposure to CER alone increased sirtuin-1 activity. Based on the present findings, we suggest that augmentation of TPP1 with enzyme replacement therapy may be a potential therapeutic option for the treatment of AD.Item New Ester-Containing Azole Derivatives With Potent Anti-Candida Effects: Synthesis, Antifungal Susceptibility, Cytotoxicity, and Molecular Modeling Studies(DRUG DEVELOPMENT RESEARCH, 2024-11) Ataker, Yusuf; Oncue, Ozge; Gulmez, Dolunay; Sabuncuoglu, Suna; Arikan-Akdagli, Sevtap; Sari, SuatMortalities due to mycoses have dramatically increased with the emergence of drug-resistant strains and growing immune-compromised populations globally. Azole antifungals have been the first choice against fungal infections of a wide spectrum and several azole derivatives with ester function were reported for their potentially promising and favorable activity against Candida spp. In this study, we designed and synthesized a series of 1-(aryl)-2-(1H-imidazol-1-yl/1H-1,2,4-triazol-1-yl)ethyl esters, and tested them against seven reference Candida strains using EUCAST reference microdilution method. Among the series, 6a, 6d, and 6g proved highly potent in vitro compared to fluconazole; especially against Candida albicans and Candida tropicalis with minimum inhibitor concentration (MIC) values as low as 0.125 and 0.06 mg/L, respectively, although their activities against Candida krusei and Candida glabrata remained limited. The compounds also showed minimal toxicity to murine fibroblasts according to the in vitro cytotoxicity tests. Molecular modeling predicted 6g as an orally available druglike compound according to all parameters and CYP51 inhibition as the likely mechanism for their antifungal effects. The study underpins the promise of azoles with ester functionality as a potential scaffold for small-molecule antifungal drug design.Item Potent Antimicrobial Azoles: Synthesis, In Vitro and In Silico Study(ANTIBIOTICS-BASEL, 2024-11) Ozdemir, Zeynep; Zenni, Yaren Nur; Karakurt, Arzu; Sari, Suat; Sarac, Selma; Akdag, Mevluet; Merde, Irem Bozbey; Kart, Didem; Venanzoni, Roberto; Flores, Giancarlo Angeles; Angelini, Paola; Kabier, Muzammil; Mathew, Bijo; Carradori, SimoneBackground/Objectives: The increase in fungal infections, both systemic and invasive, is a major source of morbidity and mortality, particularly among immunocompromised people such as cancer patients and organ transplant recipients. Because of their strong therapeutic activity and excellent safety profiles, azole antifungals are currently the most extensively used systemic antifungal drugs. Antibacterial properties of various topical antifungals, such as oxiconazole, which features oxime ether functionality, were discovered, indicating an exciting prospect in antimicrobial chemotherapy. Methods: In this study, eleven new oxime ether derivatives with the azole scaffold (5a-k) were synthesized and tested for their antimicrobial effects using the microdilution method to obtain broad-spectrum hits. Results: Although the title compounds showed limited efficacy against Candida species, they proved highly effective against dermatophytes. Compounds 5c and 5h were the most potent derivatives against Trichophyton mentagrophytes and Arthroderma quadrifidum, with minimum inhibitory concentration (MIC) values lower than those of the reference drug, griseofulvin. The MIC of 5c and 5h were 0.491 mu g/mL and 0.619 mu g/mL against T. mentagrophytes (MIC of griseofulvin: 2.52 mu g/mL). The compounds were also tested against Gram-positive and Gram-negative bacteria. Briefly, 5c was the most active against Escherichia coli and Bacillus subtilis, with MIC values much better than that of ciprofloxacin (MIC of 5c = 1.56 mu g/mL and 1.23 mu g/mL, MIC of ciprofloxacin = 31.49 and 125.99 mu g/mL, respectively). Molecular docking suggested a good fit in the active site of fungal lanosterol 14 alpha-demethylase (CYP51) and bacterial FtsZ (Filamenting temperature-sensitive mutant Z) protein. Conclusions: As a result, the title compounds emerged as promising entities with broad antifungal and antibacterial effects, highlighting the utility of oxime ether function in the azole scaffold.Item Development And Uv-Vis Spectrophotometric Analysis Of An Ease-Of-Use Pediatric Oral Solution Of Dexamethasone For Personalized Therapies(JOURNAL OF RESEARCH IN PHARMACY, 2024-10-02) Enes, Duygu; Fidan, Bilge Basak; Kaplan, Ozan; Dogan, Aysegul; Altinoz, Sacide; Celebier, Mustafa; Kaynak, Mustafa SinanThe usage of dexamethasone for pediatric applications is a well-known issue. In the present study, we developed an oral dexamethasone solution formulation especially aimed for dose-dependent personalized therapies and having excipients known as not harmful to be safely used in pediatrics. The aim of this study was to prepare an easy-of-use pediatric oral solution of dexamethasone and develop an UV/VIS Spectrophotometric method for the evaluation of the stability and quality control of the developed formulation. The primary source of dexamethasone for preparation of the oral pediatric solution was the dexamethasone one-time injectable solutions. This allowed the formulation to be easily prepared in basic laboratory conditions. Dexamethasone content and stability of the formulation were ensured by quantification using the developed UV/VIS Spectrophotometric method validated based on ICH Q2 (R1) guidelines. Simple, fast, reliable, and validated spectrophotometric analysis of dexamethasone was carried out at 269 nm wavelength and the method was linear in a range of 1.00 to 50.00 mu g mL-1.The developed formulation was stable at 4 degrees C at least for three weeks when protected from daylight. The other stability conditions (ambient temperature and -20 degrees C) were also evaluated for the assays. Although the methodology used in this study contains simple processes which can be easily adapted to basic laboratory conditions, the results were satisfactory to prepare an ease-of-use pediatric oral solution of dexamethasonefor personalized medicine. The validated UV/VIS Spectrophotometric method was selective for the formulation and easily applied for the quality control and stability studies of the samples. Such formulations could be helpful for health professionals in managing real-life corticosteroid treatment application problems especially for pediatrics in hospital pharmacy.Item Green Hplc Method For Simultaneous Determination Of N-Acetylcysteine And L-Ascorbic Acid In Co-Formulated Pharmaceutical Products(JOURNAL OF RESEARCH IN PHARMACY, 2024-10-02) Ozen, Gurkan; Nemutlu, EmirhanIt is difficult to analyze different concentrations of pharmaceutical active substances in dosage forms simultaneously, especially in formulations containing high amounts of excipients, on environmentally friendly principles without the need for any intervention. This study proposes a powerful analytical method for the simultaneous determination of L-ascorbic Acid and N- Acetyl Cysteine in an effervescent tablet using high performance liquid chromatography technique. In the study, it was aimed to reduce the use of toxic solvents/chemicals and waste emissions, to increase efficiency and to reduce the negative environmental consequences that may arise from them. The method was developed using a C18 (ACE-121-2546, 4.6 x 250 mm, 5 mu m) column and a sodium dihydrogen phosphate buffer mobile phase. Detection wavelengths were taken as 210 and 240 nm while the flow rate was 1 mL/min. The linearity, accuracy and precision, selectivity, sensitivity, and robustness of the proposed method were validated using International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use Q2R criteria and its green assessment was validated by AGREE and AGREEprep applications. The linear range was taken as 0.1-100 mu g/mL for both compounds analyzed in the developed method. The detection limit of the method was 0.02 and 0.04 mu g/mL respectively for L-ascorbic Acid and N- Acetyl Cysteine. The recovery of the method was between 98.75%102.20% and the accuracy and precision of the method for all compounds were 0.17% and 0.11% respectively. This new environmentally friendly method can be easily used by the chemical and pharmaceutical industries for regular analysis without any restrictions.Item Combination Of Miniature Electrode Systems Via Nanomaterials: Pesticide Analysis(Başkent Üniversitesi Fen Bilimleri Enstitüsü, 2024-12) Celik, Murat; Kucuk, Ipek; Sadak, Selenay; Uslu, BengiPesticides are vital in modern agriculture for controlling pests and diseases, thereby enhancing crop yields and food security. However, their extensive use has raised environmental and health concerns due to their persistence and toxicity. Conventional detection methods, such as high-performance liquid chromatography and gas chromatography, are effective but often costly and time-consuming, prompting the need for alternative approaches. Electrochemical methods emerge as promising solutions for pesticide analysis owing to their affordability, simplicity, and suitability for field applications. The incorporation of nanomaterials into electrochemical sensors significantly enhances their sensitivity and selectivity. Nanomaterials, including noble metals, carbon nanotubes, and metal oxide nanoparticles, improve sensor performance through their unique physical, chemical, and biological properties. This review examines recent advancements in miniature electrochemical sensors for pesticide detection, including contemporary literature. It discusses the structure, applications, and impacts of pesticides, and highlights the advantages of electrochemical sensors enhanced by nanomaterials. Various electrode types and their modifications with nanomaterials are evaluated. Additionally, the integration of smartphone technology and innovative approaches such as lab-on-a-chip and portable sensors are explored. By incorporating recent studies, this review provides a comprehensive reference for developing advanced, portable, and in situ analyzers utilizing nanomaterials, aiming to enhance food safety, human health, and environmental monitoring.Item Pharmacy Practice And Policy Research In Türkiye: A Systematic Review Of Literature(JOURNAL OF PHARMACEUTICAL POLICY AND PRACTICE, 2024-12-31) Gulpinar, Gizem; Pehlivanli, Aysel; Babaar, Zaheer Ud-DinBackgroundIn recent decades, there has been an interest in clinical pharmacy practice in T & uuml;rkiye with emerging studies in this area. Despite the recent emergence of diverse pharmacy practice studies in T & uuml;rkiye, a comprehensive assessment of overall typology of studies and impact has not been conducted thus far.ObjectivesThis systematic review aims to document and assess pharmaceutical policy and practice literature published within the last 5 years in T & uuml;rkiye. The other aim is to summarise the expected impact of published studies on policy and practice research.MethodsThe systematic review was conducted according to the guidelines described in the PRISMA Statement. A comprehensive search approach, incorporating Medical Subject Headings (MeSH) queries and free-text terms was employed to locate pertinent literature related to pharmacy practice and policy in T & uuml;rkiye. The search covered the period from January 1, 2019, to January 1, 2024, and involved electronic databases including PubMed, Medline Ovid, Scopus, ScienceDirect, Springer Link, PlosOne, and BMC.ResultsIn the final grouping, 73 articles met the inclusion criteria and were selected for this review. Among the quantitative studies, majority studies were cross-sectional survey studies. Through the rigorous thematic content analysis seven research domains were developed from the selected literature: drug utilisation and rational drug use, the emerging role of pharmacist, access to medicines and generic medicines, community pharmacy practice, pharmacovigilance/adverse drug reactions, and pharmacoeconomic studies.ConclusionsThe pharmacist role is evolving; however, several challenges remain in fully realising the potential of pharmacists. These include regulatory barriers, limited public awareness of pharmacists' expanded roles, workforce capacity issues, and the need for ongoing professional development and training. Research studies are needed in the areas of generic prescribing, medicine adherence, intervention studies in community and hospital pharmacy practice, and on pharmacoeconomics and pharmacovigilance.