Eczacılık Fakültesi / Faculty of Pharmacy

Permanent URI for this collectionhttps://hdl.handle.net/11727/5700

Browse

Now showing 1 - 20 of 53

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 Necmettin
Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by LC-MS/MS
(2022) Recber, Tuba; Ozkan, Ece; Nemutlu, Emirhan; Beksac, Mehmet Sinan; Kir, Sedef
Down syndrome is a common genetic disorder that results from the presence of an extra chromosome in the 21st chromosome pair of humans. Metabolomics is an alternative method in discovery of new biomarkers for the screening and diagnosis of Down syndrome. In this study, quantitative analyzes of 3-hydroxybutyric acid and 3hydroxyisovaleric acid, selected as possible markers for prenatal diagnosis of Down syndrome were performed. LCMS/MS analyzes were performed on a Phenomenex Luna NH2(100 x 4.6 mm, 3 mu m) column using a mobile phase mixture of 0.1% formic acid and acetonitrile containing 0.1% formic acid at a flow rate of 0.35 mL/minute. The MRM transitions were 103.0 -> 59.0 for 3-hydroxybutyric acid and 117.1 -> 59.0 for 3-hydroxyisovaleric acid. Under these conditions, the retention times of 3-hydroxyisovaleric acid 3-hydroxybutyric acid were 2.7 and 3.1 minute, respectively. The method was found linear from 0.1 to 10.0 mu g/mL for both metabolites. The limit of detection (LOD) was 0.017 mu g/mL for 3-hydroxybutyric acid and 0.003 mu g/mL for 3-hydroxyisovaleric acid. The lower limit quantification (LLOQ) was 0.045 mu g/mL for 3-hydroxybutyric acid and 0.008 mu g/mL for 3-hydroxyisovaleric acid. The method has been proven to be selective, precise, accurate, sensitive, and robust based on the validation studies results. Finally, the method was applied to plasma samples of the pregnant women with healthy fetus (n = 30) and with Down syndrome fetus (n = 17). As a result of the analysis, a statistically significant increase (p <0.01) was observed in the 3-hydroxybutyric acid level of the group with Down syndrome compared to the healthy group. This result strengthens the use of 3-hydroxybutyric acid as an important biomarker in the prenatal screening/diagnosis of Down syndrome.
Anti-Tyrosinase and Antimelanogenic Effect of Cinnamic Acid Derivatives from Prunus Mahaleb L.: Phenolic Composition, Isolation, Identification And Inhibitory Activity
(2023) Guven, Zuhal Bayrakceken; Saracoglu, Iclal; Nagatsu, Akito; Yilmaz, Mustafa Abdullah; Basaran, A. Ahmet; 36924865; AAI-6606-2021
Ethnopharmacological relevance: The traditional use of Prunus species against skin diseases and especially for skin lightning cosmeceutical purposes is widespread in many cultures. Prunus mahaleb L. is a well known food plant and used in the baking industry for flavoring. The fruit kernels (endocarp) are used in India for hyperpigmentation. Aim of the study: To investigate the chemical composition with the antimelanogenesis effect of P. mahaleb seed and kernel extracts and isolated compounds. Materials and methods: Isolation studies performed from the methanol extracts obtained from kernels and structures were determined using NMR and MS analysis. Antimelanogenesis effect was determined by mushroom tyrosinase assay, cellular tyrosinase assay and melanin content assay using B16F10 murine melanoma cells. Results: Five cinnamic acid derivatives were isolated and their structures (2-O-& beta;-glucopyranosyloxy-4-methoxyhydrocinnamic acid (1), cis-melilotoside (2), dihydromelilotoside (3), trans-melilotoside (4), 2-O-& beta;-glucosyloxy4-methoxy trans-cinnamic acid (5)) were elucidated using advanced spectroscopic methods. Mushroom tyrosinase enzyme inhibition of extracts, fractions and pure compounds obtained from P. mahaleb kernels were investigated and structure-activity relationship revealed. According to a detailed, comprehensive and validated LC-MS/MS technique analysis, vanilic acid (41.407 mg/g), protocatechuic acid (8.992 mg/g) and ferulic acid (4.962 mg/g) in the kernel ethylacetate fraction; quinic acid (14.183 mg/g), fumaric acid (8.349 mg/g) and aconitic acid (5.574 mg/g) were found as major phenolic compounds in the water fraction. The correlation of trace element copper content in extracts and fractions with mushroom enzyme activity was determined. By examining the enzyme kinetics of the compounds with effective cinnamic acid derivatives, inhibition types and enzyme binding constants Ki were calculated. Compounds 1,3 and 5 exhibited high noncompetitive tyrosinase inhibitory activity against L-tyrosine substrates, with IC50 values of 0.22, 0.31 and 0.37 mM respectively. In addition compounds 1, 3 and 5 showed dose-dependent inhibitory effects on intracellular tyrosinase and melanin levels in & alpha;-melanocyte-stimulating hormone (& alpha;-MSH)-induced B16F10 melanoma cells. Conclusions: Potent tyrosinase inhibitory compounds and extracts of P. mahaleb kernels suggest that it could be a new, non-toxic and inexpensive resource for the cosmeceutical industry and in skin diseases associated with hyperpigmentation.
Antimicrobial De-Escalation in Intensive Care Unit: Theory and The Reality?
(Başkent Üniversitesi Eczacılık Fakültesi, 2024-02-01) Pehlivanli, Aysel; Ozgun, Cigdem; Solmaz, Firdevs Gonca Sasal; Yuksel, Didem; Basgut, Bilgen; Ozcelikay, Arif Tanju; Unal, Mustafa Necmettin
Antimicrobial Dosing Recommendations During Continuous Renal Replacement Therapy: Different Databases, Different Doses
(Başkent Üniversitesi Eczacılık Fakültesi, 2024-03-27) Pehlivanli, Aysel; Yalcin, Tugba Yanik; Yesiler, Fatma Irem; Sahinturk, Helin; Azap, Ozlem Kurt; Zeyneloglu, Pinar; Basgut, Bilgen
Meticulous antimicrobial management is essential among critically ill patients with acute kidney injury, particularly if renal replacement therapy is needed. Many factors affect drug removal in patients undergoing continuous renal replacement therapy CRRT. In this study, we aimed to compare current databases that are frequently used to adjust CRRT dosages of antimicrobial drugs with the gold standard. The dosage recommendations from various databases for antimicrobial drugs eliminated by CRRT were investigated. The book 'Renal Pharmacotherapy: Dosage Adjustment of Medications Eliminated by the Kidneys' was chosen as the gold standard. There were variations in the databases. Micromedex, UpToDate, and Sanford had similar rates to the gold standard of 45%, 35%, and 30%, respectively. The Micromedex database shows the most similar results to the gold standard source. In addition, a consensus was reached as a result of the expert panel meetings established to discuss the different antimicrobial dose recommendations of the databases.
Antimicrobial Use In Palliative Care Service: A Prevalence Study
(Başkent Üniversitesi Eczacılık Fakültesi, 2024-02-01) Bicer, Asim Emre; Pehlivanli, Aysel; Basgut, Bilgen; Ozcelikay, Arif Tanju
Azole Rings Linked To Cox Inhibitors Via Hydrazone Bridge: Synthesis, Stereochemical Analysis, And Investigation Of Antimicrobial Activity
(Başkent Üniversitesi Eczacılık Fakültesi, 2024-04-19) Karaguzel, Ayse; Ugur, Suemeyye Buran; Cetinkaya, Yasin; Dogan, Senguel Dilem; Stevanovic, Milena; Nikodinovic-Runic, Jasmina; Gunduz, Miyase Gozde
Nonsteroidal anti-inflammatory drugs (NSAIDs) alleviate inflammation and pain through the inhibition of cyclooxygenase (COX) enzymes. Besides these widely recognized therapeutic utilizations, NSAIDs have been reported to display moderate antimicrobial activity and enhance antimicrobial efficacy when administered in combination with commercial antimicrobial drugs. In the present study, we designed novel potential antimicrobial agents by linking some NSAIDs (ibuprofen, flurbiprofen, and naproxen) to various azole rings (pyrazole, imidazole, triazole, and benzimidazole) via hydrazone functionality. The hydrazone linker was introduced into the chemical scaffold of the title molecules by the reaction between hydrazides obtained from NSAIDs and inhouse synthesized azole-carrying benzaldehydes. The structures of the target compounds were elucidated by a combination of spectral methods. The NOESY spectra and stereochemical analyses performed using DFT method confirmed the presence of the target molecules as a mixture of E(C=N)-E(N-N)-synperiplanar and E(C=N)-E(N-N)antiperiplanar conformers in DMSO-d6 solution. 1H and 13C NMR chemical shift values in DMSO were calculated using the GIAO method and compared with the experimental NMR data. Finally, some derivatives were demonstrated to inhibit Candida albicans filamentation and/or bacterial communication system known as quorum sensing. For COX inhibitor-azole hybrids with antimicrobial potency, naproxen appeared to be the most appropriate NSAID, while bulky benzimidazole was not found as a preferable azole ring.
Azoles Display Promising Anticonvulsant Effects Through Possible Ppar-Α Activation
(Başkent Üniversitesi Eczacılık Fakültesi, 2024-05-25) Sari, Suat; Yurtoglu, Sibel; Zengin, Merve; Marcinkowska, Monika; Siwek, Agata; Sarac, Selma
Azoles such as nafimidone, denzimol and loreclezole are known for their clinical efficacy against epilepsy, and loreclezole acts by potentiating gamma-aminobutyric acid (GABA)-ergic currents. In the current study, we report a series of azole derivatives in alcohol ester and oxime ester structure showing promising anticonvulsant effects in 6 Hz and maximal electro shock (MES) models with minimal toxicity. The most promising of the series, 5f, was active in both 6 Hz and MES tests with a median effective dose (ED50) of 118.92 mg/kg in 6 Hz test and a median toxic dose (TD50) twice as high in mice. The compounds were predicted druglike and blood-brain barrier (BBB) penetrant in silico. Contrary to what was expected, the compounds showed no in vitro affinity to GABAA receptors (GABAARs) in radioligand binding assays; however, they were found structurally similar to peroxisome proliferator-activated receptors alpha (PPAR-alpha) agonists and predicted to show high affinity and agonist-like binding to PPAR-alpha in molecular docking studies. As a result, 5f emerged as a safe azole anticonvulsant with a wide therapeutic window and possible action through PPAR-alpha activation.
A Bayesian Estimation Framework for Pharmacogenomics Driven Warfarin Dosing: A Comparative Study
(2015) Oztaner, Serdar Murat; Temizel, Tugba Taskaya; Erdem, S. Remzi; Ozer, Mahmut; 0000-0002-7537-2170; 25020183; AAJ-2370-2021
The incorporation of pharmacogenomics information into the drug dosing estimation formulations has been shown to increase the accuracy in drug dosing and decrease the frequency of adverse drug effects in many studies in the literature. In this paper, an estimation framework based on the Bayesian structural equation modeling, which is driven by pharmacogenomics, is proposed. The results show that the model compares favorably with the linear models in terms of prediction and explaining the variations in warfarin dosing.
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, Pelin
Extracellular 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.
Chymotrypsin and Trypsin Inhibitory Activity of Some Medicinal Plants Collected from Rize (Türkiye)
(Başkent Üniversitesi Eczacılık Fakültesi, 2024-02-25) Gunbatan, Tugba; Sucu, Melike; Gokbulut, Alper; Dilmac, Elif; Gurbuz, Ilhan
In this research, the evaluation of in vitro chymotrypsin and trypsin inhibitory activities of ten plant species collected from Rize were aimed, and fractions that showed strong activity were analyzed through HPLC. Daphne pontica L. and Mentha longifolia (L.) L. were found to have the highest chymotrypsin inhibitory activities (87.75 and 84.24 % inhibition). Similarly, the highest trypsin inhibitory activity was observed in D. pontica (%99.93 inhibition), followed by Sambucus ebulus L. flowers (87.47 % inhibition). Extracts showing strong enzyme inhibition were fractioned and subjected to activity tests. The highest chymotrypsin inhibitory activity was observed in the n-hexane fraction of D. pontica (%80.70 inhibition), while the highest trypsin inhibitory activity was found in the n-butanol fraction of S. ebulus (%86.81 inhibition). HPLC studies determined that the 80 % ethanol extract of D. pontica and its dichloromethane and ethyl acetate fractions contained umbelliferone. It was found that chlorogenic acid was present in the 80 % ethanol extracts of S. ebulus flowers. M. longifolia was found to contain chlorogenic acid, caffeic acid, luteolin-7-glucoside, and rosmarinic acid. M. longifolia has been identified as the plant exhibiting the highest antioxidant activity in ABTS and CUPRAC tests, consistent with its high phenolic and flavonoid content.
Clinical pharmacist assessment of drug-related problems among intensive care unit patients in a Turkish university hospital
(2022) Albayrak, Aslinur; Basgut, Bilgen; Bikmaz, Gulbin Aygencel; Karahalil, Bensu; 35033079
Background Critically ill patients treated in the intensive care units (ICUs) often suffer from side effects and drug-related problems (DRPs) that can be life-threatening. A way to prevent DRPs and improve drug safety and efficacy is to include clinical pharmacists in the clinical team. This study aims to evaluate the classification of drug-related problems and the implementation of clinical pharmacy services by a clinical pharmacist in the ICU of a university hospital in Turkey. Methods This study was carried out prospectively between December 2020 and July 2021 in Gazi University Medical Faculty Hospital Internal Diseases ICU. All patients hospitalized in the intensive care unit for more than 24 h were included in the study. During the study, the clinical pharmacist's interventions and other clinical services for patients were recorded. DRPs were classed according to the Pharmaceutical Care Network Europe V.8.02. Results A total of 151 patients were included during the study period corresponding to 2264 patient-days. Patients with DRPs had a longer hospital stay and a higher mortality rate (p < 0.05). 108 patients had at least one DRP and the total number of DRPs was 206. There was an average of 1.36 DRPs per patient, 71.5% of patients experienced DRP and 89.22 DRPs per 1000 patient-days. A total of 35 ADEs were observed in 32 patients. ADE incidence was per 1000 patient-days 15.45. ADEs were caused by nephrotoxicity (48.57%), electrolyte disorders (17.14%), drug-induced thrombocytopenia (17.14%), liver enzyme increase (8.57%) and other causes (8.57%). Drug selection (40.29%) and dose selection (54.36%) constituted most of the causes of DRPs. Dose change was the highest percentage of planned interventions with a rate of 56.79%. Intervention was accepted at a rate of 90.8% and it was fully implemented. Conclusion In this study, the importance of the clinical pharmacist in the determination and analysis of DRPs was emphasized. Clinical pharmacy services like the one described should be implemented widely to increase patient safety.
Combination Of Miniature Electrode Systems Via Nanomaterials: Pesticide Analysis
(Başkent Üniversitesi Fen Bilimleri Enstitüsü, 2024-12) Celik, Murat; Kucuk, Ipek; Sadak, Selenay; Uslu, Bengi
Pesticides 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.
Community Pharmacists Preparedness and Barriers for Cancer Health Promotion in North Cyprus
(2023) Bosah, Dubem Henry; Birand, Nevzat; Basgut, Bilgen; https://orcid.org/0000-0002-5883-5583; 35234102; JKS-4834-2023
Introduction The role of a community pharmacist is well recognized in the literature as the most accessible health care provider that promotes health wellness and disease prevention. Evidence supports their role in cancer health promotion though this is not seen yet in practice. The aim of the study was to assess community pharmacists' preparedness in terms of knowledge, role perception and barriers for providing cancer health promotion in North Cyprus. Methods A cross-sectional face-to-face questionnaire-based study was carried among a randomly selected representative sample of community pharmacists in North Cyprus between June 2020 and August 2020. A pre-validated 31-item questionnaire tool was revised by an expert panel and adopted for purpose of this study. Results 200 (64.5%) out of 310 approached community pharmacists' have accepted and responded to the questionnaire of which 183 were fully answered. The community pharmacists' awareness of cancer was moderate, as 70% answered correctly. Most respondents (93.4%) agree that pharmacists should be involved in cancer health promotion. Most respondents (> 90%) agree that pharmacist's lack of interest in oncology, lack of educational material and pharmacist's hesitancy about their knowledge of cancer are respectively the most important barriers for cancer health promotion. Conclusion The study shows that community pharmacist well perceives their role in cancer health promotion despite moderate awareness of cancer related facts and hesitancy of their knowledge necessary for assuming their role. Lack of interest, motivation and cancer educational materials availability are also major barrier to address.
Comparative Plant Metabolomics of Momordica charantia Seeds and Fruits
(Başkent Üniversitesi Eczacılık Fakültesi, 2024-03-30) Enes, Duygu; Fidan, Bilge Basak; Basaran, Arif Ahmet; Celebier, Mustafa
Momordica charantia L., Cucurbitaceae, known mainly as karela, bitter gourd or bitter melon, and balsam pear, is used for antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer, and anti-inflammatory and wound healing. This study aimed to elucidate the differences in the metabolites of 70% methanol extracts of M. charantia seeds and fruit using untargeted metabolomics. Liquid chromatography coupled to quadrupole time-of-flight mass spectrometry-based analysis of the extracts for both seed and fruit was performed using a C-18 column. Differences were observed in seed and fruit extracts, which were visualized using principal component analysis plots. (R)-Salsolinol, pantetheine, coumarin, tryptamine, lysophospholipidPC(O-18:0), glucosylceramide, pyroglutamic acid, and presqualene diphosphate in the seed and fruit of M. charantia were detected in different levels. The amount of lysophospholipidPC(O-18:0) (lysoPC(O-18:0)) and glucosylceramide is high in the fruit, while the amount of (R)-salsolinol, pantetheine, coumarin, tryptamine, presqualene diphosphate, and pyroglutamic acid is high in the seed. These primary untargeted metabolomic results revealed that the different pharmacological effects may be related to the variable amounts of some specific metabolites in seeds and fruits.
Comparison of in vitro activities of plazomicin and other aminoglycosides against clinical isolates of Klebsiella pneumoniae and Escherichia coli
(2021) Ince, Gizem; Mirza, Hasan Cenk; Guclu, Aylin Uskudar; Gumus, Hale; Erol, Cigdem; Basustaoglu, Ahmet; 0000-0001-9071-9606; 0000-0002-1872-028X; 0000-0002-2535-2534; 0000-0002-8853-3893; 34499728; AAJ-2108-2021; AAU-6196-2020; AAJ-1219-2021; F-1232-2015
Objectives: To compare the in vitro activity of plazomicin and two older aminoglycosides (gentamicin and amikacin) against 180 isolates of Escherichia coli and Klebsiella pneumoniae, including subsets of 60 non-ESBL-producing, 60 ESBL-producing and 60 carbapenem-resistant (46 carrying bla(OXA-48), 11 carrying bla(NDM) and 3 carrying bla(OXA-48) and bla(NDM)) strains. Methods: MICs of plazomicin, gentamicin and amikacin were determined by a gradient diffusion method. Gentamicin and amikacin MICs were interpreted according to CLSI criteria and EUCAST breakpoint tables. Plazomicin MICs were interpreted using FDA-defined breakpoints. Results: All non-ESBL-producing and ESBL-producing isolates were susceptible to plazomicin. The plazomicin susceptibility rate (71.7%) in carbapenem-resistant isolates was significantly higher than those observed for gentamicin (45%) and amikacin (56.7% and 51.7% according to CLSI and EUCAST breakpoints, respectively). Gentamicin, amikacin and plazomicin susceptibility rates (35.6% for gentamicin; 44.4% and 37.8% for amikacin according to CLSI and EUCAST breakpoints, respectively; 64.4% for plazomicin) in carbapenem-resistant K. pneumoniae were significantly lower than those observed for carbapenem-resistant E. coli isolates (73.3% for gentamicin; 93.3% for amikacin and plazomicin). Gentamicin, amikacin and plazomicin susceptibility rates for bla(NDM)-positive isolates were lower than those observed for bla(OXA-48)-positive isolates, but differences were not statistically significant. Among the isolates that were non-susceptible to both gentamicin and amikacin, the plazomicin susceptibility rate was less than 30%. Conclusions: Although plazomicin showed excellent in vitro activity against carbapenem-susceptible isolates, the plazomicin resistance rate increased to 35.6% among carbapenem-resistant K. pneumoniae and further increased to 45.5% among bla(NDM)-positive isolates.
Cyclodextrin-Based Nanogel Of Flurbiprofen For Dermal Application: In Vitro Studies And In Vivo Skin Irritation Evaluation
(2022) Oktay, Ayse Nur; Celebi, Nevin; Ilbasmis-Tamer, Sibel; Kaplanog, Guelnur Take
The aim of this study was to develop and characterize flurbiprofen (FB)-loaded cyclodextrin (CD) based nanogel formulations for dermal application. Nanogels were produced via emulsification solvent evaporation and then incorporated into a hydroxypropyl methyl cellulose (HPMC) gel. The visual examination, pH, viscosity, dynamic rheological measurements and drug content analysis of nanogels were assessed. In vitro and ex vivo permeation, stability, and skin irritation were performed. pH of the FB-loaded nanogel and the nanogels in HPMC were 10.6 +/- 0.1 and 7.5 +/- 0.1 (neutral) respectively. The highest and lowest viscosities were observed in FB-loaded nanogels and in FB-free nanogels in HPMC, respectively. The tangent delta and storage modulus values of FB-loaded nanogel in HPMC were higher than those of FB-loaded nanogel. FB from nanogels in HPMC was 100% by 48 h. The final nanogel formulation was physically and chemically stable over 12 months. Skin irritation test showed no skin irritation or cellular infiltration on the histological level. In vitro and ex vivo permeation showed that the nanogels could be effective and stable formulations, especially in the dermal application of a hydro-phobic molecule.
Detection of COVID-19 by Machine Learning Using Routine Laboratory Tests
(2021) Cubukcu, Hikmet Can; Topcu, Deniz Ilhan; Bayraktar, Nilufer; Gulsen, Murat; Sari, Nuran; Arslan, Ayse Hande; 0000-0002-1219-6368; 0000-0002-7886-3688; 34791032; E-3717-2019; Y-8758-2018
Objectives The present study aimed to develop a clinical decision support tool to assist coronavirus disease 2019 (COVID-19) diagnoses with machine learning (ML) models using routine laboratory test results. Methods We developed ML models using laboratory data (n = 1,391) composed of six clinical chemistry (CC) results, 14 CBC parameter results, and results of a severe acute respiratory syndrome coronavirus 2 real-time reverse transcription-polymerase chain reaction as a gold standard method. Four ML algorithms, including random forest (RF), gradient boosting (XGBoost), support vector machine (SVM), and logistic regression, were used to build eight ML models using CBC and a combination of CC and CBC parameters. Performance evaluation was conducted on the test data set and external validation data set from Brazil. Results The accuracy values of all models ranged from 74% to 91%. The RF model trained from CC and CBC analytes showed the best performance on the present study's data set (accuracy, 85.3%; sensitivity, 79.6%; specificity, 91.2%). The RF model trained from only CBC parameters detected COVID-19 cases with 82.8% accuracy. The best performance on the external validation data set belonged to the SVM model trained from CC and CBC parameters (accuracy, 91.18%; sensitivity, 100%; specificity, 84.21%). Conclusions ML models presented in this study can be used as clinical decision support tools to contribute to physicians' clinical judgment for COVID-19 diagnoses.
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 Sinan
The 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.
Development of Cyclosporine A Nanosuspension: Cytotoxicity and Permeability on Caco-2 Cell Lines
(2021) Celebi, Nevin; 34931593
Cyclosporine A is a calcineurin inhibitor and is usually used as an immunosuppressant medication. The main purpose of this study is to develop nanosuspension of polypeptide cyclosporine A by using the wet milling method for oral administration. Cell culture studies were also performed with human intestinal Caco-2 cell lines. Hydroxypropyl methylcellulose and sodium dodecyl sulfate were used as stabilizers in nanosuspension. In vitro characterization studies such as Fourier-transform infrared analysis and morphological imaging with scanning electron microscopy have been carried out with obtained cyclosporine A nanosuspension. The particle size, particle size distribution, and zeta potential values of the nanosuspension were measured approximately 400 nm, 0.4, and -25 mV, respectively. The solubility of cyclosporine A was increased 4.5 times in nanosuspension compared to the coarse cyclosporine A powder. As a result of cytotoxicity studies conducted with different concentrations, it was decided to conduct permeability studies at a dose equivalent to 150 mu g/mL cyclosporine A. Permeation studies have shown that the nanosuspension increases cyclosporine A transport by 5 and 1.5 times, respectively, compared to coarse powder and commercial product.