Eczacılık Fakültesi / Faculty of Pharmacy
Permanent URI for this collectionhttps://hdl.handle.net/11727/5700
Browse
11 results
Search Results
Item Ceftobiprole Mono-Therapy Versus Combination Or Non-Combination Regimen Of Standard Antibiotics For The Treatment Of Complicated Infections: A Systematic Review And Meta-Analysis(Başkent Üniversitesi Eczacılık Fakültesi, 2024-06-10) Jame, Wissal; Basgut, Bilgen; Abdi, AbdikarimObjective: Various bacteria produce complicated infections that are difficult to treat worldwide. Ceftobiprole is effective against resistant Gram-positive and Gram-negative bacteria. Methods: This review assessed effectiveness and safety of ceftobiprole monotherapy for severe infections. A systematic review and meta-analysis of randomized controlled trials comparing clinical cure, microbiological cure, and safety of ceftobiprole alone to a combination or non-combination antibiotic regimen was conducted. Until December 20, 2022, we searched a major databases. Results: This study includes 4168 patients from six trials. Ceftobiprole and comparator-received patients had similar clinical responses for all patient population. Also, the eradication rate of all organisms and specific pathogenic bacteria in microbiologically examined patients was comparable between the groups. Ceftobiprole induced more gastrointestinal side events than comparable drugs, mostly nausea [OR 1.91 (1.26-2.90), p = < 0.01]. While skin-related adverse events were significantly associated with comparator antibiotics [6 trials, 4062 patients; OR 0.77 (0.60-0.99), p=0.03]. Conclusion: Ceftobiprole monotherapy is effective and safe for severe infections caused by Gram-positive or Gram-negative bacteria.Item 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, SelmaAzoles 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.Item 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, MustafaMomordica 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.Item 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 GozdeNonsteroidal 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.Item 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, BilgenMeticulous 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.Item 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, IlhanIn 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.Item 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 NecmettinItem 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 TanjuItem 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 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.