Turkish Journal of Pharmaceutical Sciences最新文献

Objectives: The purpose of this study was to investigate the effect of Olea europaea L. leaf extract (OLE) on senescence and senescence-associated secretory phenotype (SASP) caused by temozolomide (TMZ) in glioblastoma (GB).

Materials and methods: A senescence β-galactosidase assay and a colony formation assay were used to determine the effects of OLE, TMZ, and OLE + TMZ on the cellular senescence and aggressiveness of GB cell lines T98G and U87MG. mRNA expression levels of p53, a senescence factor, interleukin (IL)-6, matrix metalloproteinases (MMP)-9, and nuclear factor kappa B1 (NF-κB1) as SASP factors and Bcl-2 and Bax as senolytic markers were assessed using quantitative reverse transcription-real-time polymerase chain reaction. Cells were double-stained with acridine orange and propidium iodide to observe the cell morphology.

Results: TMZ increased the senescence rate of GB cells (p<0.001). Besides, OLE + TMZ reduced the proportion of senescent cells (p<0.001) and their capability to form colonies compared to TMZ-only-treated cells. Additionally, OLE + TMZ co-treatment elevated the mRNA expression levels of MMP-9, IL-6, NF-κB1, p53, and the Bax/Bcl-2 ratio compared to TMZ-only treatment. Especially in U87MG cells, involvement of OLE in TMZ treatments increased more than six times in the Bax/Bcl-2 ratio compared to TMZ-only, which induced the apoptosis-like morphological features (p<0.0001).

Conclusion: Collectively, our findings presented the inhibitory effect of OLE on TMZ-mediated SASP-factor production in GB and, accordingly, its potential contribution to elongate the time of recurrence.

Objectives: Aim of the current study was to evaluate the stress-protective effect of oligopeptides-homologues of the adrenocorticotropic hormone (ACTH) fragment 15-18 on morphogenetic signs of stress reaction of the adrenal glands under acute cold exposure (CE) in rats.

Materials and methods: The acute cold stress was reproduced by placing random-bred male rats in a freezer at a temperature of -18°C for 2 hours. The peptides-homologous of ACTH_15-18 acetyl-(D-Lys)-Lys-Arg-Arg-amide (KK-1) and acetyl-(D-Lys)-Lys-(D-Arg)-Arg-amide (KK-5) and the reference medicine (Sema) were administered intranasally in a dose of 20 mg/kg 30 minutes before and after CE. Rectal temperature was measured before and 10 min after CE. Zona glomeruloza, zona fasciculata, zona reticularis, and the area of cells and nuclei of adrenocorticocytes of the zona fasciculata were measured.

Results: KK-1 significantly prevented structural changes in the adrenal cortex and medulla and stabilized the secretory activity of glucocorticoid-producing cells. However, the congestion of the capillaries of the zona fasciculata and zona reticularis remained in some locations. Zona fasciculata cells had a marked tendency to decrease, and the area of nuclei significantly decreased (p<0.05) recovering the width to control animals' markers. KK-5 had a more marked recovery of the adrenal glands (a greater saturation of cytoplasm of adrenocorticocytes of zona glomerulosa and zona fasciculata). The number of chromaffin cells at rest was increased in the adrenal medulla. KK-5 statistically significantly normalized both the area of cells (p<0.05) and the area of nuclei (p<0.05) of the zona fasciculata, unlike KK-1, which reliably restored only the marker of the nuclei area. Some morphometric parameters of acute stress hypertrophy remained in the adrenal glands of rats receiving Sema.

Conclusion: KK-1 and KK-5 prevented the manifestation of acute stress reactions in the adrenal cortex of rats. KK-5 had a more marked stress-protective effect compared with the peptide KK-1. Both study substances exceeded the reference medicine Sema. KK-5 is a promising stres-sprotector and frigoprotector.

Objectives: This study aimed to develop a Turkish scale to assess medication literacy and to evaluate its psychometric properties among adults having at least 12 years of education in Türkiye.

Materials and methods: After the composition of a preliminary set of items, the content validity of the scale was assessed by an e-Delphi process and a pilot study. The psychometric properties of the scale were evaluated in 358 participants, who had above 12 years of education: university students, academics and, administrative staff from two faculties (pharmacy and law) in two universities located in two major cities (İstanbul and Ankara) in Türkiye between March and May, 2021. The test-retest validity was assessed by Spearman's rho and Wilcoxon test. Internal consistency was evaluated by Kuder Richardson 20. Principal component analysis was conducted.

Results: The last version of the medication literacy scale consisted of 8 items. There was a positive correlation (Spearman's rho: 0.570; p<0.01) and no significant difference (p=0.308) between the scores of the scale at baseline and after a two-week interval. Kuder Richardson 20 coefficient was 0.659. Students and graduates of health sciences and participants with high reading ability of health-related information had significantly higher scores on the medication literacy scale (p<0.001).

Conclusion: Turkish version of the Medication Literacy Scale for Adults is a valid tool for evaluate medication literacy among adults, who have above 12 years of education in Türkiye. The generalizability of our findings should be evaluated with caution since this study was conducted in a sample with a significant representation from healthcare professionals. It would be useful to conduct further studies evaluating the psychometric properties of this scale in participants with diverse characteristics.

The recently explained cytokine, which is produced after the stimulation of interferon (IFN)-c, interleukin (IL)-2, and IL-18 is IL-32, has pro-inflammatory IFN-c, IL-2 and IL-18 are IL-32 mediator's properties that are generally entailed in many diseases, including infections, cancer, and chronic inflammation. After the initial statement in 2005, it promoted the osteoclast precursor's differentiation into TRAcP plus VNR plus multinucleated cells that express explicit osteoclast indicators. Furthermore, the loss of bone resorption might be accredited because of the collapse of the multinucleated cells, which are produced of the reaction to IL-32 to direct factoring that is ultimately essential for attaching the cells for bone resorption. Thus, in conclusion, IL-32, the pro-inflammatory mediator, has an important and indirect role in regulating osteoclast differentiation. In bone disorder's pathophysiology, critical role of IL-32 needs more scientific evidence to develop a rational treatment protocol. IL-32 can become a potent mediator of active osteoclast generation in the presence of receptor activator of NF-κB ligand (RANKL). This novel cytokine can introduce more favorable conditions for osteoclastogenesis in the rheumatic arthritis by increasing the RANKL and osteoprotegerin ratio in fibroblast-like synoviocytes.

Objectives: Early detection of bone cancer is critical for treating symptoms, minimizing pain, and increasing overall quality of life. It is critical to develop novel radiopharmaceuticals with high labeling efficiency and stability for the diagnosis of bone cancer. This research aims to design a novel radiopharmaceutical that may be used to diagnose bone cancer.

Materials and methods: In this study, ibandronate sodium (IBD), a bisphosphonate analog, was radiolabeled with technetium-99m [^99mTc] and quality control tests on the newly developed radiopharmaceutical ([^99mTc]Tc-IBD) were performed using radioactive thin layer chromatography. After that, the incorporation of [^99mTc]Tc-IBD into hydroxyapatite (HA) crystals and a human bone osteosarcoma cell line (U2OS) was tested.

Results: According to the results obtained, optimal radiolabeling procedure was obtained for [^99mTc]Tc-IBD with 200 μg.mL^-1 IBD, 20 μg stannous chloride, and ^99mTc with 37 MBq radioactivity. The reaction mixture was adjusted to pH 5.5 and incubated at room temperature for 15 min. The radiochemical purity of [^99mTc]Tc-IBD was found to be greater than 95% at room temperature for up to 6 h. Additionally, chromatography analysis showed >95% [^99mTc]Tc-IBD complex formation with promising stability for up to 24 h in saline and up to 2 h in cell medium. The percentage binding of IBD to HA was 83.70 ± 3.67 and the logP of [^99mTc]Tc-IBD was -1.1014. The radiolabeled complex exhibited a higher rate of cell incorporation to U2OS cells compared to Reduced/Hydrolyzed ^99mTcO₄ -.

Conclusion: The newly produced radiopharmaceutical is very promising according to the results of in vitro cell culture, HA binding, and quality studies, and will be a step forward for further studies in nuclear medicine for bone cancer diagnostics.

Objectives: Respiratory tract infections (RTIs) are common in children. To treat the symptoms of simple health problems, individuals look for natural healing methods that can be easily prepared at home. The aim of this study was to determine the plants and herbal products used by the parents of children suffering from viral upper respiratory tract symptoms by questionaire. In the study, applications and products, other than plants used by families for their children were also investigated.

Materials and methods: This study is a cross-sectional survey conducted at Faculty of Medicine, Gazi University (Ankara, Türkiye). A questionnaire form was used by scanning the existing literature and reviewed with the patients face to face by the researchers. The data obtained from the study were analyzed with the Statistical Package for the Social Sciences (SPSS) statistical program.

Results: About half of the participants reported that they used non-chemical drug practices for their children with upper RTIs. The most common practice was to prepare herbal tea (30.5%), followed by mandarin/orange and/or their juice (26.9%) for oral application. The most used herbal tea for upper RTIs is with linden (Tilia sp.). Patients who used linden usually prepared it as tea, in other words by infusion, and served their children 1-2 cups/1-3 times a week. Except for herbal tea, the participants mostly used honey (19.0%) for their children's symptoms.

Conclusion: Where available, appropriate doses and dosage forms of herbal supplement products with scientifically proven efficacy and safety should be determined for the pediatric population. Parents should use these products based on the recommendations of their pediatrician.

Objectives: The intracellular parasitic protozoan, Leishmania spp., causes several forms of diseases in humans. Cytotoxicity and emergence of new strains resistance to the current anti-leishmanial drugs have encouraged researchers to focus on new resources. Glucosinolates (GSL) are found mainly in the Brassicaceae family with potential cytotoxic and anti-parasitic properties. The present study reports in vitro antileishmanial activity of the GSL fraction from Alyssum linifolium seeds against Leishmania major.

Materials and methods: The GSL fraction was prepared by ion-exchange and reversed-phase chromatography. For the assessment of antileishmanial activity, the promastigotes and amastigotes of L. major were treated with different concentrations of the fraction (75-625 μg/mL).

Results: The IC₅₀ was 245 µg/mL for anti-promastigote effect of the GSL fraction and 250 µg/mL for its anti-amastigote effect that had a significant difference (p<0.05) with both glucantime and amphotericin B. The selectivity index of the GSL fraction (15.8), to glucantime and amphotericin B, was greater than 10, indicating the selective effect of this fraction against L. major amastigotes. Glucoiberverin was the major constituent of the GSL fraction characterized using nuclear magnetic resonance and electron ionization-mass spectrometry spectra. Based on gas chromatography-mass spectrometry data, iberverin and iberverin nitrile, the hydrolysis constituents from glucoiberverin, included 76.91% of the total seed volatiles.

Conclusion: The results suggest that GSLs like glucoiberverin could be considered a new promising candidate for further studies on antileishmanial activity.

Objectives: Olmesartan medoxomil (OLM) and metoprolol succinate (MPS) in fixed-dose combination (FDC) tablet formulation prescribed extensively. Stability indicating (SI) method for impurities and related substance (RS) test quantitates the amount of these analytes in formulation; the manuscript presents SI/RS-ultra-high performance liquid chromatography-photodiode array (UHPLC-PDA) method for OLM and MPS and their impurities.

Materials and methods: Well-resolved separation of all analytes was achieved with gradient elution on a Shimadzu on Shimpack GIST-C18 (100 mm x 2.1 mm, 2 µm) column maintained at 25°C. Mobile phase-A consist of 0.1% orthophosphoric acid in water and mobile phase-B was acetonitrile at a flow rate of 0.4 mL/min, data integrated at 225 nm and 16 min of short runtime for satisfactory elution of all peaks.

Results: The proposed SI/RS-UHPLC-PDA method was developed and validated as per International Conference on Harmonisation (ICH) of Technical Requirements guidelines. The system suitability test complied by all eluted peaks of the interest with acceptable linearity, recovery, and precision. Specificity, robustness, and method sensitivity parameters were determined; all the parameters were found to be within the limits. All the impurities and stress-degraded peaks were well resolved.

Conclusion: The proposed method was found to be simple, fast, linear, and accurate. Further, the method is precise, robust, and specific; suitable for routine IPQC during active pharmaceutical ingredient manufacturing, stability and impurity profiling studies of the titled bulk analytes. Furthermore, the method can be extended to assess the levels of impurities formed during life cycle of new FDCs of titled analytes.

Objectives: The development of antimicrobial molecules discussed with considerable achievement over the past decades provided many classes of semisynthetic or synthetic compounds. Resistance to many antimicrobial agents requires the discovery of novel molecules.

Materials and methods: In this study, ten ethylparaben hydrazide-hydrazone derivatives, the previously reported, were evaluated for their in vitro antibacterial and antifungal activities. The microbroth dilution method was used for the determination of the minimum inhibitory concentration (MIC) values of the novel molecules.

Results: The antimicrobial activities of the molecules were found in a wide range with MIC values of 2-256 μg/mL. The synthesized compounds showed good to moderate antimicrobial activity compared with the standards. Among the synthesized molecules, compound 3g showed the best antimicrobial activity at 2 μg/mL against Staphylococcus aureus strain (ATCC 29213).

Conclusion: Ethylparaben hydrazide-hydrazone compounds in our study were found to have antimicrobial activities. Ethylparaben is currently used as an antibacterial agent and preservative for preparations. These studies are necessary since they detect the relationship between the substitutions and activity.