Vaccine-induced immunity wanes over time and warrants booster doses. We investigated the long-term (32 weeks) immunogenicity and safety of a third, homologous, open-label booster dose of TURKOVAC, administered 12 weeks after completion of the primary series in a randomized, controlled, double-blind, phase 2 study. Forty-two participants included in the analysis were evaluated for neutralizing antibodies (NAbs) (with microneutralization (MNT₅₀) and focus reduction (FRNT₅₀) tests), SARS-CoV-2 S1 RBD (Spike S1 Receptor Binding Domain), and whole SARS-CoV-2 (with ELISA) IgGs on the day of booster injection and at weeks 1, 2, 4, 8, 16, 24, and 32 thereafter. Antibody titers increased significantly from week 1 and remained higher than the pre-booster titers until at least week 4 (week 8 for whole SARS-CoV-2) (p < 0.05 for all). Seroconversion (titers ≥ 4-fold compared with pre-immune status) persisted 16 weeks (MNT₅₀: 6-fold; FRNT₅₀: 5.4-fold) for NAbs and 32 weeks for S1 RBD (7.9-fold) and whole SARS-CoV-2 (9.4-fold) IgGs. Nine participants (20.9%) tested positive for SARS-CoV-2 RT-PCR between weeks 8 and 32 of booster vaccination; none of them were hospitalized or died. These findings suggest that boosting with TURKOVAC can provide effective protection against COVID-19 for at least 8 weeks and reduce the severity of the disease.

In this study, we wanted to investigate the effectiveness of combining disease‐modifying anti‐rheumatic drugs (DMARD) with hyperbaric oxygen therapy (HBOT) in reducing inflammation in a rheumatoid arthritis (RA) model using rats. We divided 56 male Sprague–Dawley rats into seven groups and induced RA using complete Freund's adjuvant. Some groups received HBOT, whereas others were given etanercept or leflunomide. We started the treatment on the 10th day after inducing RA and continued it for 18 days. To evaluate the effectiveness of the treatments, we measured paw swelling and used X‐rays to examine the joints before and after the treatment. We also analysed the levels of two inflammatory markers, tumour necrosis factor (TNF)‐α and interleukin (IL)‐1β, using an enzyme‐linked immunosorbent assay. Additionally, we conducted histological analysis and assessed the expressions of anti‐IL‐1β and anti‐TNF‐α antibodies. All the treatment groups showed a significant decrease in arthritis scores, paw swelling and levels of TNF‐α and IL‐1β. The X‐ray images revealed improvements in joint structure, and the histopathological analysis showed reduced inflammation and collagen abnormalities. Combining DMARD with HBOT had similar effects to individual therapies, suggesting a cost‐effective and potentially safer approach for improving outcomes in rats with RA.

This bioequivalence research aims to evaluate the relative bioavailability and pharmacokinetic characteristics of ethinyl estradiol and drospirenone in the test preparation in comparison to the reference preparation during fasting conditions. A liquid chromatography method with tandem mass spectrometry was used to determine the concentrations of drospirenone and ethinyl estradiol in plasma. The pharmacokinetic parameters that were analyzed were the maximum plasma concentration (C_max), time to achieve C_max (t_max), elimination half life, and area under the concentration time curve of plasma (AUC_0‐t, AUC_0‐∞ for ethinyl estradiol, and AUC_0‐72h for drospirenone). Both the AUC and C_max parameters were determined to be between 80.00% and 125.00% (90% confidence intervals), which is the acceptable range. Based on the study findings, it was concluded that the test formulation, which includes 3 mg of drospirenone and 0.03 mg of ethinyl estradiol, demonstrated bioequivalence when compared to the reference formulation.

This study aimed to evaluate the effects of dextromethorphan (DX), alone and in combination with gemcitabine (GEM), on cell viability, apoptosis, and epithelial–mesenchymal transition (EMT) markers in PANC-1 human pancreatic cancer cells. PANC-1 human pancreatic cancer cells were cultured and treated with varying concentrations of dextromethorphan (DX), gemcitabine (GEM), and 5-fluorouracil (5-FU), both as monotherapies and in combination. Cytotoxic effects were assessed using the MTT assay, and IC₅₀ values were calculated at 24, 48, and 72 h. Apoptotic responses were evaluated using Annexin V-FITC/PI staining followed by flow cytometry. Protein expression levels of Bax, Bcl-2, and Vimentin were determined via immunocytochemistry, while EMT markers (E-cadherin, N-cadherin, Vimentin) were analyzed using flow cytometry. Relative mRNA expression of apoptotic and EMT-related genes was quantified by qRT-PCR. DX exhibited time- and dose-dependent cytotoxicity in PANC-1 cells, with IC₅₀ values of 280.4 µM at 24 h, 163.2 µM at 48 h, and 105.6 µM at 72 h. For GEM, the 72 h IC₅₀ was 57.53 µM. The combination of DX 50 µM + GEM 12.5 µM resulted in significantly lower cell viability (24.93 ± 3.12%) compared to GEM 25 µM (35.33 ± 5.22%) and DX 100 µM (51.40 ± 3.10%) (p < 0.001). Flow cytometry revealed significant increases in early (21.83 ± 1.32%) and late apoptotic cells (32.20 ± 0.84%) in the combination group, with a corresponding reduction in viable cells compared to control (24.93 ± 3.12% vs. 89.53 ± 0.97%, p < 0.001). Immunocytochemical analysis showed increased Bax-positive cell count (62.0 cells/unit area), and decreased Bcl-2 (19.0) and Vimentin (28.0) levels in the combination group compared to control (Bax: 15.0, Bcl-2: 60.0, Vimentin: 70.0) (p < 0.001). Flow cytometry for EMT markers demonstrated increased E-cadherin (83.84 ± 0.65%) and decreased Vimentin (71.04 ± 1.17%) and N-cadherin (30.47 ± 0.72%) expression in the DX + GEM group compared to EMT control (E-cadherin: 68.97 ± 1.43%, Vimentin: 91.00 ± 0.75%, N-cadherin: 62.47 ± 1.13%) (p < 0.001). qRT-PCR supported these findings with increased Bax (2.1-fold), E-cadherin (2.0-fold), and reduced Bcl-2 (0.3-fold) and XIAP (0.6-fold) in the combination group (p < 0.05). Dextromethorphan, particularly in combination with gemcitabine, appears to enhance apoptosis and suppress EMT-associated marker expression in PANC-1 cells, supporting its potential as an adjuvant agent in pancreatic cancer therapy.

This study aims to determine the bioequivalence of the reference preparation and the test preparation containing eltrombopag when both were given during the COVID-19 pandemic while fasting. Participants in the research were healthy male Caucasian subjects. One film-coated tablet of the test preparation or one film tablet of the reference preparation, equivalent to 75 mg of eltrombopag, was given to the participants in a randomized order throughout each treatment session. At pre determined blood sampling points, blood samples were taken to determine the pharmacokinetics of eltrombopag. Eltrombopag concentrations in the samples were determined using an LC-MS/MS technique verified using ESI(−). The study results were used to calculate the rate (the maximum plasma concentration, or Cmax) and extent (area under the concentration-time curve of plasma, or AUC(0−72) and AUC(0−t) of eltrombopag absorption from the test preparation and reference preparation. The 90% confidence intervals (CI) of the ln-transformed AUC(0−72), AUC(0−t), and Cmax of eltrombopag met the bioequivalence requirements of 80.00–125.00%. Both trial preparations had a similar and very satisfactory safety profile.

Aim: To evaluate prescriptions issued for patients diagnosed with hypertension in terms of rational drug use and cost-effectiveness. Methods: This retrospective observational study was conducted using prescriptions issued for patients diagnosed with essential hypertension in the central district of Kayseri, Turkey. Data were obtained from the Medulla Provision System, encompassing prescriptions that included at least one antihypertensive drug and were covered by national health insurance during January 2019. Prescriptions were evaluated based on patient demographics (age and sex), prescribed antihypertensive drugs (pharmacological group and active ingredient), physician specialty, and healthcare institution, presence of comorbidities at treatment initiation and follow-up, and conformity of the chronic disease report to clinical guidelines. Results: The study included 1,968 prescriptions, with a mean patient age of 63.97 ± 11.88 years. Rational drug use (RDU) was significantly higher in the 18–64 age group (81.6%) compared to those aged ≥80 years (88.9%) (χ² = 6.123, p = 0.039), and among males (84.8%) versus females (80.8%) (χ² = 5.123, p = 0.024). Prescriptions from general practitioners showed significantly lower RDU rates compared to those from cardiologists and internists. RDU was observed in 83.6% of patients without asthma using beta-blockers, while only 21.1% of asthmatic patients on beta-blockers met RDU criteria (χ² = 43.089, p < 0.001). Prescriptions with three active ingredients had the lowest RDU rate (70.9%), compared to those with one (85.0%) or two (88.3%) ingredients (χ² = 70.976, p < 0.001). The median treatment cost was significantly lower in the RDU group (10.72 USD) than in the non-RDU group (11.76 USD) (z = 4.076, p < 0.001). Although not statistically significant (p = 0.081), the highest RDU rate was observed in prescriptions containing generic imported drugs (26.0%). Cost analysis showed that original imported drugs had the highest unit cost (2.85 USD), while generic imported drugs had the lowest (1.90 USD) (p < 0.001). Conclusion: This study demonstrated that adherence to rational drug use principles in the treatment of hypertension, aligned with current clinical guidelines, results in safer and more cost-effective therapeutic outcomes. Rational prescribing was associated with lower drug counts per prescription and reduced treatment expenditures. However, the widespread use of beta-blockers, particularly outside of their recommended indications, and the preference for original branded products indicate areas for improvement. To enhance rational prescribing practices, awareness must be increased at all levels of the healthcare system, and policy-driven targets should be developed accordingly.