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Background and Aims: Bloodless surgical field during functional endoscopic sinus surgery (FESS) is an essential part, and research continues to find simple and effective regime for it. This study was aimed to compare the efficacy of oral clonidine versus oral metoprolol as premedicants regarding surgical field condition and controlled hypotension in patients undergoing FESS. Material and Methods: Sixty-eight patients of American Society of Anesthesiologists (ASA) physical status (PS) I and II aged 18–60 years, of both genders, scheduled for FESS under general anesthesia were randomly allocated in two groups. Group C (n = 34) received oral clonidine 300 μg and group M (n = 34) received oral metoprolol 50 mg, 2 h before surgery. Controlled hypotension (mean arterial pressure [MAP] 65–75 mmHg) was achieved by titrating sevoflurane (1%–3%). Primary outcome measured was surgical field visualization by Average Category Scale (ACS 0–5), and the secondary outcomes measured were hemodynamic parameters, sevoflurane requirement, recovery, and side effects. Categorical, continuous, and ordinal data were compared using Chi-square test, t-test, and Mann–Whitney test, respectively. P < 0.05 was considered as statistically significant. Results: ACS was significantly less in group C compared to group M up to 60 min, (P < 0.05). Mean systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP were significantly less in group C compared to group M at all time intervals (P < 0.05) Intraoperative sevoflurane requirement (vol %) was significantly less in group C (1.21 ± 0.42) compared to group M (1.68 ± 0.53) (P = 0.000). Conclusions: Premedication with oral clonidine was found to be superior to oral metoprolol as it provided significantly better surgical field condition during FESS with much efficient controlled hypotension and anesthetic-sparing effect. Standardized Study Reporting Requirements: CONSORT: http://www.consort-statement.org/.

Background and Aims: Emergence agitation (EA) is frequently encountered following nasal surgeries, and postoperative pain is a significant contributing element. We aimed to assess the role of suprazygomatic maxillary nerve (MN) block (SMB) guided by ultrasound (US) in lowering EA incidence and enhancing analgesia quality in septorhinoplasty cases. Material and Methods: Sixty cases aged 18–60 years, of both genders, categorized by the American Society of Anesthesiologists (ASA) I–II and listed for septorhinoplasty, were randomized to receive general anesthesia (GA) with either no block (the control group) or combined with bilateral US-guided SMB (the SMB group). The incidence of EA, postoperative pain scores, total rescue 24-hour analgesic consumption, and incidence of adverse events were all noted. Results: EA incidence was significantly reduced in the SMB group than in the control group (five patients (16.7%) vs 14 patients (46.6%), respectively; P = 0.026). Pain scores at 30 minutes and 1, 2, 4, and 6 hours postoperative were significantly decreased in the SMB group (P = 0.024, 0.000, 0.000, 0.009, and 0.038, respectively), with significantly less morphine consumption at 24 hours postoperative in the SMB group compared with the control group (P = 0.000). No serious adverse events were noted. Conclusions: Preemptive application of US-guided SMB was effective in lowering EA incidence. Furthermore, it enhanced the analgesic quality and reduced the requirement for rescue analgesics in patients undergoing septorhinoplasty.

Background and Aims: Open pyeloplasty in children is associated with considerable postoperative pain. The paravertebral block (PVB) is commonly performed to control postoperative pain in such surgeries. Erector spinae plane block (ESPB) has recently been described as effective in providing postoperative analgesia in pediatric abdominal surgeries. This randomized, assessor-blinded study compared postoperative analgesic effects between ESPB and PVB in children undergoing pyeloplasty. Material and Methods: Eighty pediatric patients scheduled for elective pyeloplasty were randomly allocated to receive either ultrasound-guided (USG) ESPB or PVB. Postoperative pain evaluation was done using the face, legs, activity, cry, and consolability (FLACC) scale for children up to 7 years of age and the visual analog scale (VAS) for children in the age group between 7 and 10 years at 0, 2, 4, 8, 12, and 24 h. The time of first rescue analgesia, the number of doses of analgesic, successful first puncture rate, and block-related complications were noted. Results: No significant differences were noted in the FLACC/VAS scores, duration of time to first rescue analgesia (575.90 ± 118.81 vs. 617.05 ± 144.20, P = 0.168), the number of rescue doses once and twice over 24 h was 72.5% versus 67.5% and 27.5% versus 32.5% (P = 0.626) between ESPB vs PVB. The incidence of hematoma at the block site was higher in the PVB group (10%) compared to the ESPB group (0%) (P = 0.04). The incidence of first puncture success in the block was better in ESPB (P = 0.003). Conclusions: Both ESPB and PVB can be effectively used for controlling post-pyeloplasty pain in children. The ease of performing the block and the relatively lower incidence of hematoma at the block site make ESPB more advantageous.

Background and Aims: Control of the hemodynamic response during intubation is essential. To assess the effect of age on the median effective dose (ED50) and 95% effective dose (ED95) of fentanyl for blunting the hemodynamic response to intubation. Material and Methods: Patients (n = 86) undergoing general anesthesia were randomly stratified according to age (groups 1–4); fentanyl was administered to each patient according to the Dixon and Massey method, starting at 2 μg/kg. The dose was increased or decreased by 0.5 μg/kg for the subsequent patient, depending on the failure or success of blunting of the hemodynamic response, respectively. Success was defined as a change in heart rate and blood pressure by

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are severe, socially significant diseases that require a clear understanding of the relationship between the current health status and quality of life of patients. On the one hand, in the scientific literature, there is not enough data to assess the quality of life for the different therapeutic regimens, and no specific tools have been developed to assess functional indicators and health status. On the other hand, with the exception of Rituximab treatment, the available immunosuppressive regimens do not lead to a good clinical response in patients with AAV. The aim of the study is to measure health-related quality of life in a Bulgarian population of patients with systemic vasculitis associated with ANCA undergoing biological treatment with Rituximab by using the generic instrument SF-36 version 2. We conducted a retrospective-prospective, non-interventional, controlled study in two periods in two centers in Bulgaria. Treatment with Rituximab leads to qualitative and quantitative improvement in all components of physical health, including mental and social components. After treatment, all measured parameters were within the normal range for the general population.

Abstract Background Patients with chronic kidney disease (CKD) are at risk of developing conditions such as atherosclerosis and inflammation-induced anemia (AI) due to persistent inflammation. Ziltivekimab, an antibody targeting interleukin-6, is being studied for its potential to reduce inflammatory markers in these patients. Methods Following PRISMA guidelines, we searched for relevant randomized controlled trials (RCTs) up to August 20, 2023, and analyzed the data using RevMan 5.4 software. The study period spanned from February 18, 2023, to September 23, 2023. We assessed efficacy outcomes such as high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), and both high-density lipoprotein (HDL) and low-density lipoprotein (LDL), as well as safety outcomes, including adverse events (AEs) and infections. Pooled results were calculated using the random effects model and inverse variance method, with mean differences (MD) and risk ratios (RR) presented alongside 95% confidence intervals (CI). Results Our review included three RCTs with a total of 473 patients. Compared to the placebo group, patients treated with ziltivekimab showed significantly lower levels of hs-CRP, fibrinogen, and SAA (MD = − 51.64, 95% CI [− 73.73 to − 29.56], P

Abstract Background Neonatal hyperbilirubinemia is a prevalent condition that affects newborns, characterized by elevated serum bilirubin levels. The accumulation of bilirubin can cause neurotoxicity, resulting in various complications, and in severe cases, even mortality. The underlying pathophysiology of this condition primarily involves an inconsistency between the synthesis and excretion of bilirubin. Despite the short- and long-term side effects of phototherapy, it is considered a core treatment of neonatal hyperbilirubinemia. Exchange transfusion is considered a last resort in cases where phototherapy fails. Several studies have investigated the use of various agents either to replace phototherapy or to be added as adjuvants to reduce the time required for phototherapy and hence minimize the adverse effects. Some of these studies have demonstrated positive outcomes, indicating their effectiveness, while others have failed to yield any significant differences in treatment duration. Main text The present review summarized the etiology of neonatal hyperbilirubinemia. It was demonstrated that neonatal hyperbilirubinemia has mainly two types: Conjugated and unconjugated hyperbilirubinemia. Treatment options for neonatal hyperbilirubinemia were discussed with phototherapy as the most prevalent and successful option followed by exchange transfusion. Side effects of phototherapy were also discussed together with the different approaches introduced to clinical practice to minimize these side effects. Conclusion Phototherapy is the most successful treatment of neonatal hyperbilirubinemia, although its side effects are of great concern. Studies introducing adjuvants such as zinc sulfate and ursodeoxycholic acid have demonstrated promising results in reducing the duration of phototherapy and minimizing the side effects. However, these results are inconclusive, and further research is required to validate the safety and efficacy of these adjuvants.

Abstract Background The CDSCO of India has authorized a combination of metformin hydrochloride, teneligliptin hydrochloride, and pioglitazone hydrochloride for the treatment of insulin-independent diabetes. For the purpose of estimating metformin, teneligliptin, and pioglitazone combinations as well as individual commercial formulations, there are a plethora of publicly accessible chromatographic techniques. More importantly, the development of these chromatographic procedures has included the use of chemical solvents that are dangerous to both animals and the environment. Objectives However, to date, there has been no documented chromatographic technique that can concomitantly estimate various commercial formulations of drugs under study employing a uniform chromatographic condition and environmentally friendly solvents. In order to concomitantly estimate drugs under study utilizing unified chromatographic conditions, a green HPTLC method was developed. Method The AQbD approach was used to carry out the method development. To determine the most important method parameters and response variables, the analytical risk assessment was conducted using the risk priority number ranking and screening approach. Critical method parameters and response variables were modeled using the response surface modeling approach, which relies on the central composite design. Optimal ranges for the intended method operable design region were determined, and control strategy was framed. The chromatographic separation was carried out on preparative TLC plate precoated with silica gel G-60 F254 using 1.0%W/V ammonium acetate in ethanol: water: triethylamine (6.5:0.4:0.6, V/V) as mobile phase. The detection of the anti-diabetic drugs under study was carried out at 267 nm wavelength. Results The linearity of metformin, teneligliptin, and pioglitazone was found to be 5000–25000 ng/band, 200–1000 ng/band, and 150–750 ng/band, respectively. The %RSD for robustness and precision study was found to be less than 2.0%. The %recovery of method was found to be 98–102%. The assay results were shown to be in compliance with respective labeled claims of anti-diabetic medications when the suggested method was used for concurrent analysis of several formulations and combinations of drugs under study. Conclusion The suggested technique was evaluated utilizing red–green–blue model scoring tools. The suggested technique was determined to be precise, accurate, rapid, cost-effective, and easy to apply for the estimation of drugs under study.

Abstract The rising incidence of neurodegenerative diseases represents a significant global health concern. The prognosis for such diseases is often unfavorable, and patients require supportive treatment to manage their condition effectively. The present study investigated the anti-oxidative, anti-acetylcholinesterase (anti-AChE) effect of hydro-alcoholic extract of Sansevieria cylindrica leaves and Plumeria obtusa seed pods in Wistar rats. Plants were authenticated followed by pharmacognostic evaluation. The antioxidant and anti-AChE activities were evaluated by scopolamine-induced oxidative stress and acetylcholine level alterations in Wistar rats. On the 0th, 7th, and 14th days during study period behavioral parameters were evaluated, including open field test, new object recognition test, and Morris water maze task. Different antioxidant enzymes were also evaluated in brain homogenate post 7 days treatment. AChE levels in rats’ brains were assessed post 14 days of treatment. Finally, histopathology of brains samples was performed. Correspondingly, in-vitro and in-silico studies were done to support the study findings. Results Sansevieria cylindrica and Plumeria obtusa exhibited strong antioxidant and anti-AChE activities due to secondary metabolites content. Rearing and, line crossing by rats showed substantial alteration (p

Abstract Background This study presents the development and validation of a UV spectrophotometric method for the simultaneous estimation of teneligliptin hydrobromide hydrate (TEN) and pioglitazone hydrochloride (PIO) in pharmaceutical dosage forms. The method measures absorbance at 243 nm for TEN and 265 nm for PIO. Validation was conducted according to ICH guidelines, covering specificity, linearity, range, precision, accuracy, limit of detection, limit of quantification, and robustness. Results The method exhibited linearity in the 2–25 µg/ml concentration range for both TEN and PIO, with correlation coefficients close to 1. Precision studies showed low % RSD values, indicating excellent repeatability and minimal intra- and inter-day variability. Accuracy was confirmed through recovery studies, with results within the 98–102% range. The method demonstrated sensitivity with low LOD and LOQ values. Robustness testing showed stability and consistency under varying conditions. Analysis of tablet formulations confirmed the accurate quantification of both drugs. Conclusion The developed UV spectrophotometric method offers a simple, sensitive, and cost-effective solution for the simultaneous estimation of TEN and PIO in pharmaceutical formulations. It is suitable for routine analysis and quality assessment of tablet dosage forms.

Abstract Background Curcumin is an age old traditional medicine. Although curcumin has several advantages, its water solubility and bioavailability limit its use as a natural therapeutic agent. Polymeric nano curcumin could be an excellent option to overcome these challenges to augment its therapeutic efficacy. This work aimed to synthesize curcumin-loaded PLGA nanoparticles and assess their angiogenic and antioxidant potential in the zebrafish model. Results The double emulsion solvent evaporation process was employed to make curcumin-loaded PLGA nanoparticles. Curcumin showed ~ 28.23 (± 2.49) encapsulation efficacy with an average diameter of PLGA nanoparticles 168.5 (± 2.5) nm and curcumin nanoparticles about 281.6 (± 17.2) nm, respectively. The curcumin nanoparticles showed no developmental toxicity to the zebrafish embryos while reduced toxicity compared to the native curcumin. Further, the curcumin nanoparticles reduced the generation of reactive oxygen species and improved angiogenesis in the model system. All these results confirmed that the nanoparticle has had higher bio-efficacy than that of native curcumin. Conclusion This study shows that PLGA curcumin nanoparticles hold an excellent therapeutic promise for wound healing, tissue regeneration and other biomedical applications where angiogenesis and ROS play critical role.

Abstract Background In recent years, antibiotic resistance rates have become a global concern for clinicians to combat the pathogenic bacteria associated with UTIs. The objective of this current paper is to explore the evidence-based use of natural products as an alternative strategy to reduce the recurrence rates among different UTI patient populations such as pregnant women, postmenopause women, and children. Main body Commonly used non-antimicrobial products to treat and prevent UTIs include vaginal estrogen, cranberry, probiotics, D-mannose, hyaluronic acid (HA), Chinese herbal medicine, and ascorbic acid. Literature supports the safety and effectiveness of utilizing these products in different UTI patients to a great extent. The strongest recommendation was given to the utilization of vaginal estrogen replacement therapy in postmenopausal females to prevent rUTI. Conclusion We believe our research is the first to provide evidence-based clinical practice guidelines and insight into UTI management using non-antimicrobial drugs in different populations. Our findings can guide future research on the reduction of antimicrobial misuse and preventing antimicrobial resistance. Graphical Abstract

Abstract Objective Dual‐antiplatelet therapy (DAPT) and proton pump inhibitor (PPI) are frequently prescribed after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) placement. However, studies that evaluate the optimal PPI when used as primary prevention in patients without a history of peptic ulcer disease or upper gastrointestinal bleeding (UGIB), particularly in the context of DAPT involving prasugrel, are lacking. This study aimed to assess the efficacy and safety of PPI use in preventing UGIB in this patient population. Methods This study included patients who underwent PCI with coronary stent placement for acute coronary syndrome or stable angina at our institution from January 2015 to December 2020. Eligible patients started DAPT with aspirin and prasugrel and concomitantly received PPI therapy (lansoprazole or esomeprazole), with a follow-up period of two years. The primary endpoint was UGIB incidence, diagnosed during follow-up, serving as an efficacy measure. Secondary endpoints included the assessment of major bleeding (as defined by the Thrombolysis in Myocardial Infarction major bleeding criteria) and clinically relevant non-major bleeding events. Safety outcomes focused on adverse event incidence attributable to PPI use. Results Among the 165 patients analyzed, 109 and 56 were included in the lansoprazole and esomeprazole groups, respectively, with cumulative incidence of UGIB at 96 weeks of 0.9% (1/109) and 3.6% (2/56). No significant differences in terms of major bleeding events or other bleeding outcomes were observed between the two groups. Adverse events related to PPI use were reported as diarrhea/soft stools in 7 (6%) cases and thrombocytopenia in 1 (1%) case in the lansoprazole group, whereas no such events were observed in the esomeprazole group. No clinically significant hematologic or biochemical abnormalities were reported. Conclusion This study evaluated the efficacy and safety of PPIs in combination with DAPT, including prasugrel, following PCI, and suggests that lansoprazole and esomeprazole may offer comparable efficacy in preventing UGIB.

Abstract Background Aminoglycosides are crucial for treating multidrug-resistant gram-negative infections and endocarditis. However, aminoglycosides are associated with significant risks of nephrotoxicity, necessitating careful dose selection and therapeutic drug monitoring. Therapeutic drug monitoring is essential for minimizing risk; however, few institutions routinely perform it. This study aimed to assess the impact of a pharmacist-driven therapeutic drug monitoring intervention on aminoglycoside usage trends and clinical outcomes. Methods This retrospective cohort study included 263 patients treated with aminoglycosides between 2014 and 2023. A pharmacist-led therapeutic drug monitoring intervention began in 2017, focusing on monitoring renal function, documenting patient weight, and closely managing aminoglycoside concentrations. Trends in aminoglycoside use and renal outcomes were analyzed. Results Over the study period, appropriate use of aminoglycosides at the time of initial prescription increased from 49 to 82% (P

Abstract Background and Objective Accurate and robust adverse event (AE) data collection is crucial in cancer clinical trials to ensure participant safety. Frameworks have been developed to facilitate the collection of AE data and now the traditional workflows are facing renewal to include patient-reported data, improving completeness of AE data. We explored one of these workflows in a cancer clinical trial unit. Methods The study was a single-site study conducted at a tertiary hospital located in Australia. Patients consenting to a clinical trial were eligible for inclusion in this study. Participants used an electronic platform—My Health My Way (MHMW)—to report their symptomatic data weekly for 24 weeks. A symptom list was included within the platform, along with a free text field. Data reported via the platform was compared with data recorded in the patient’s medical chart. Time taken to compile data from each source was recorded, along with missing data points. Agreement between patient-reported data and data recorded in the medical notes was assessed using Kappa and Gwet’s AC1; time taken to compile data and missing data points were assessed using a Wilcoxon signed rank test. Results Low agreement was found between patient- and clinician-reported data (− 0.482 and − 0.159 by Kappa and Gwet’s AC1 respectively). Only 127 (30%) of the total 428 AEs were reported by both MHMW and medical notes. Patients reported higher rates of symptoms from the symptom list, while clinicians reported higher rates of symptoms outside of the symptom list. Time taken to compile the data from MHMW was significantly less than that taken to review medical notes (2.19 min versus 5.73 min respectively; P

Abstract Introduction Psychotropic drugs have been reported to cause urinary retention (UR) via anticholinergic and other mechanisms. However, UR has not received much attention because of its non-fatal symptoms. We investigated the occurrence of UR associated with psychotropic drugs using the Japanese Adverse Drug Event Report (JADER) database. Methods Using the JADER database, we calculated reporting odds ratios for UR for 74 psychotropic drugs. Multivariate logistic regression analysis was used to adjust for the effects of sex, underlying disease, and age on UR. Variable selection included forced entry for sex, age, benign prostatic hyperplasia (BPH), depression, and backward-forward stepwise selection for each drug. Results A total of 887,704 cases were reported, of which 4653 (0.52%) had UR. In terms of sex, 0.79% (3401/429,372 cases) and 0.43% (1797/415,358 cases) of male and female patients had UR. In terms of age, 0.31% (892/288,676 cases) and 0.68% (3463/506,907 cases) of patients aged < 60 years and 60 years or older had UR. Among the underlying diseases, 8.22% (930/11,316 cases) and 0.43% (3723/876,388 cases) of patients with BPH and without BPH had UR, respectively. Further, 1.99% (337/16,959 cases) and 0.50% (4316/870,745 cases) of patients with depression and without depression had UR, respectively. Overall, 38 psychotropic drugs met the criteria for signal detection. In logistic regression, a total of 783,083 patients of discernible age and sex were included. The selected variables were sex, age, BPH, depression, and 23 drugs, including quetiapine [adjusted reporting odds ratio (ROR) 95% confidence interval (CI): 1.46–2.81], chlorpromazine (adjusted ROR 95%CI: 1.29–3.13), etizolam (adjusted ROR 95%CI: 1.47–3.09), maprotiline (adjusted ROR 95%CI: 1.99–8.34), mirtazapine (adjusted ROR 95%CI: 1.37–2.88), and duloxetine (adjusted ROR 95%CI: 2.15–4.21). Conclusions Many psychotropic drugs induce UR, which may be owing to their pharmacological effects. Appropriate monitoring is needed, especially in patients with other risk factors for UR.

Abstract Background Hemophilia A (HA) treatment strategies aim to manage bleeding episodes and improve patients' quality of life. This study investigates the effectiveness of a preventative approach using intermediate-dose prophylaxis with standard half-life FVIII products in reducing bleeding rates and enhancing the quality of life for patients with severe HA. Methods A 4-year prospective longitudinal study followed 35 patients with severe HA (without FVIII inhibitors) who transitioned from a reactive treatment approach to intermediate-dose prophylaxis in Taiwan from 2014 until 2018. The study tracked annual bleeding rates (ABR) and annual joint bleeding rates (AjBR) alongside associated costs and patient-reported quality-of-life measures. Results Prophylaxis significantly reduced both ABR and AjBR compared with the previous treatment. After one year, ABR and AjBR decreased by 76.9% and 72.5%, respectively, with further reductions to 91.0% and 90.8% after 4 years (p

New 3-hydroxy-1,3-diaryl-2,3,5,6,7,8-hexahydro-imidazo[1,2-a]pyridine-1-ium bromides have been designed, synthesized, and characterized by 1Н NMR, 13C NMR, and LCMS. The cyclic structure of the condensation products of aryl-(3,4,5,6-tetahydropyridin-2-yl)amines with α-bromoketones has been proven. It has been shown that heating 3-hydroxy-1,3-bis-(41-methoxyphenyl)-2,3,5,6,7,8-hexahydro-imidazo[1,2-a]pyridine-1-ium bromide in acetic anhydride accompanied by elimination of water to form 1,3-bis-(41-methoxyphenyl)-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridine-1-ium bromide. Antitumor activity of 1,3-bis-(41-ethoxyphenyl)-3-hydroxy-2,3,5,6,7,8-hexahydro-imidazo[1,2-a]pyridine-1-ium bromide and 1,3-bis-(41-methoxyphenyl)-5,6,7,8-tetrahydro-imidazo[1,2-a]pyridine-1-ium bromide have been studied. The fully aromatic imidazo[1,2-a]pyridine-1-ium bromide system was shown to have a higher antitumor effect. According to the screening results, the tested compound showed a significant level of anticancer effect on cancer cells of colon COLO 205 (lgGI50 = -5.35, lgTGI = –4.70 and lgLC50 = –4.19) and melanoma SK-MEL-5 (lgGI50 = –5.57, lgTGI = –4.81 and lgLC50 = –4.17).

Background: The Italian university system is actively revising the Master of Pharmacy (MPharm) curriculum to reflect post-COVID healthcare needs and a greater clinical focus. Understanding the challenges and opportunities faced by Italian pharmacists that relocated to Great Britain (GB) might provide valuable insights regarding the transferability of knowledge and skills obtained in the Italian pharmacy degree. Aim: The study aimed to capture the perceptions of Italian pharmacists practising in GB regarding the Italian pharmacy degree programme and to explore the challenges and opportunities they face in their new professional environment, ultimately to inform the Italian government and related stakeholders (Ministry of University and Research, MUR) about the need to update the Italian MPharm curriculum to make it more clinically relevant and aligned with international standards. Materials and methods: The authors developed a 50-item survey, pilot tested and reviewed for face and content validity by an expert panel. Participants’ characteristics, reasons for moving to GB, and data on their experience of practising as a pharmacist in Italy and GB were collected using Likert-type items and open- and closed-ended questions. Convenience sampling was used, and a sample power calculation was not deemed necessary. Statistical analysis involved descriptive analysis presenting frequencies and percentages for Likert-type and categorical items. Results: An estimated 281 pharmacists qualified in Italy are registered with the General Pharmaceutical Council in GB. Of these, 54 took part in the survey, resulting in a probable coverage of the sample population of 19.2%. Respondents pointed to the lack of job satisfaction and limited future perspectives as the main reasons to leave Italy (38.9% and 83.3%, respectively). Other reasons to relocate to GB were clinically focused job opportunities and better salaries (68.5% and 79.6%, respectively). Notably, almost two-thirds of the participants affirmed that Italian pharmacy degrees were insufficient to meet the requirements for practising as a pharmacist in GB. Conclusion: Different approaches to teaching clinical pharmacy and practical aspects seen in the pharmacy degree programmes in Italy and GB highlight a clear need for aligning the Italian pharmacy curriculum with the modern requirements of the pharmacy profession. Additionally, this alignment would facilitate the movement of Italian pharmacists into the GB healthcare system and beyond.

This study evaluates the dual anti-viral and anti-bacterial activity of Tridax procumbens using system biology and molecular docking targeting the tumor necrosis factor (TNF) signaling pathway. The bioactive potential of Tridax procumbens was studied using phytochemical databases, and the essential biomolecules were selected for the study. The principle of geneVenn diagrams and protein target prediction was used to identify overlapping molecular targets with viral and bacterial diseases, which was later validated using various database mining tools like GeneCards and OMIM. Cytoscape software was applied to construct protein-protein interaction networks, which showed that TNF, AKT1, EGFR, SRC, and ESR1 are the hub genes of the networks. The gene ontology (GO) enrichment analysis also recapitulated the modulated biological processes, cellular components, and molecular functions of Tridax procumbens compounds, including their action on the TNF signaling in inflammation and immune responses. Molecular docking studies showed strong binding affinities of compounds such as cynaroside and 5,7,2,3,4-Pentahydroxy-3,6-dimethoxyflavone 7-glucoside to TNF, and molecular dynamics simulations confirmed these interactions’ stability. The findings suggest that Tridax procumbens exerts its therapeutic effects by modulating the TNF signaling pathway, offering significant anti-viral and anti-bacterial properties. This integrative approach provides insights into the Tridax procumbens’s mechanisms of action, supporting its potential as a source of novel therapeutic agents against infectious and bacterial diseases. There is still a need for further experimental research to define the full spectrum of Tridax procumbens’ therapeutic application.

Rheumatoid arthritis (RA) is a progressive and chronic systemic autoimmune disease. However, currently treatment is often carried out using NSAIDs and corticosteroids. Although it reduces symptoms, this treatment has a high rate of side effects. This study aims to determine the anti-inflammatory property of Curcuma heyneana so that it can be used as an alternative treatment for RA. Based on author knowledge, this study on C. heyneana from the Indonesian region for the treatment of RA is still limited. C. heyneana’s rhizome was extracted by maceration with ethanol followed by fractionation process using n-hexane, ethyl acetate, and n-butanol. The anti-inflammatory invitro activities were determined by heat-induced hemolysis, effect on protein denaturation, and cyclooxygenases (COX) inhibition assay. Molecular docking of major predictive compounds was performed by AutoDock Vina. The results showed that some fractions of C. heyneana contained terpenoids, flavonoids, and alkaloids. The ethyl acetate fraction exhibited the highest anti-inflammatory activity, which was attributed to the presence of curcuminoids. Molecular docking studies further confirmed the potential of demethoxycurcumin, a curcuminoid identified in the ethyl acetate fraction, to inhibit COX-2. These findings suggest that C. heyneana, particularly its previously unreported curcuminoid-rich fractions, holds promise as a natural anti-inflammatory agent. Further research is warranted to explore the therapeutic potential of this plant in the management of RA and other inflammatory disorders.

The purpose of this study is to formulate and evaluate amphiphilic cream with meloxicam indicated for topical relief of pain, particularly because there are currently no available topical dosage forms on the market. Thus, the present research is focused on characterization of the capacity of the amphiphilic base, composed of glycerol monostearate, cetyl alcohol, Tagat® S2, Myritol® 318, propylene glycol, and white petrolatum, to be loaded with drug model meloxicam dissolved in propylene glycol. To enhance the solubility and penetration of meloxicam, menthol as a rubefacient was added to the meloxicam solution. The series of three formulations were prepared with variable content of added menthol. Obtained creams were characterized by drug content, pH, spreadability, viscosity, microbial purity, drug release, and stability. Results showed stable cream formulations with good spreadability and viscosity, suitable for topical application.

Abstract Background Lung cancer (LC) remains a predominant global health concern, especially with escalating tobacco-smoking rates. Present study provides computational screening, molecular dynamics, DFT and simulation analysis of phytoconstituents on EGFR receptors (2ITY and W2O), followed by selection of highest docking score phytoconstituents among 45 for further analysis. The formulation was optimized by Central composite design. Nanostructured-lipid carriers were prepared by high-speed homogenization, combining a 1:1 ratio of liquid lipid (Castor oil) and melted solid lipid (glyceryl monostearate) with 4% surfactant (tween 80) in a water phase containing Glycyrrhizin. The resulting mixture underwent high-speed homogenization at 8000 rpm for 40 min, followed by sonication for 15 min to achieve formulation development of GNLC. The anticancer potential of GNLC have been proved by experimental analysis through MTT assay using A549 Cell lines. Results Glycyrrhizin was found to possess maximum docking score − 8.863 and − 8.837 on both 2ITY and W2O respectively. The study unveils Glycyrrhizin’s interactions with EGFR pivotal in cancer progression and treatment. Molecular dynamics simulations highlighted the structural and dynamic interactions within a protein–ligand complex, indicating both stability and flexibility characteristics. DFT analysis of Glycyrrhizin revealed its molecular properties, suggesting stability and potential reactivity. Glycyrrhizin loaded nanostructured lipid carriers (GNLC) have been developed and analysed by various parameters like particle size and drug release zeta potential, SEM analysis, and solubility analysis reveals critical insights into their optimization for effective drug delivery. Both GNLC and Doxorubicin (0.78–50 µg/ml) were used for the activity. The anticancer potential at 12.50, 25 and 50 µg/ml pf GNLC was found to be statistically significant and was comparable with that of standard group Doxorubicin. The observed structural transformations in Glycyrrhizin into a lipid matrix indicate potential enhancements in its drug release. Conclusions GNLC shows promising anti-cancer potential in lung cancer, further pre-clinical and clinical studies, is crucial to validate its efficacy, safety, and integration into standard therapeutic regimens. Graphical abstract

Abstract Background Lung cancer remains a leading cancer type, but current chemotherapy is limited by issues including poor drug delivery, toxicity, and resistance. To address these challenges, we developed a novel PLGA-PEG-LHRH (PPL) nanoconjugate system for improved drug delivery. Curcumin, known for its anticancer and P-gp inhibition properties, was co-loaded with bcl2siRNA (bclsR) to inhibit the bcl2 protein, thus overcoming both resistance mechanisms. Results The PPL conjugate was successfully synthesized and characterized using FTIR, 1H NMR, XRD, XPS and BCA assay. Curcumin and bclsR-loaded PLGA nanoemulsions were prepared by double emulsion solvent evaporation method and characterized. The optimized nanoconjugate had size of 179 ± 16 nm, favorable zeta potential, high drug entrapment, and was confirmed via TEM. Controlled release studies indicated 83% drug release within 24 h. In vitro studies revealed significant cytotoxicity against A549 lung cancer cells, with the nanoconjugate showing IC50 of 8.24 µg/mL compared to 21.26 µg/mL for plain curcumin. Enhanced cellular uptake and effective targeting of A549 cells were observed. Molecular analyses demonstrated significant downregulation of MDR1 and Bcl2 RNA and protein expression, highlighting the nanoconjugates' ability to suppress resistance mechanisms. Pharmacokinetic studies in Wistar rats showed superior plasma drug concentrations, half-life, and AUC for the nanoconjugate versus pure drug suspension. Biodistribution studies showed increased drug accumulation in the lungs. In vivo efficacy studies in Balb/c mice demonstrated higher tumor inhibition ratios for CUR-siRNA PPL NPs (66.89%) and CUR-PPL NPs (59.84%) which was further confirmed with TNFα and p53 levels in blood. Histopathological studies showed good healing in the CUR-siRNA PPL NP- and CUR-PPL NP-treated mice compared to suspension. Conclusion From the study, it may be concluded that the PPL nanoconjugate system, loaded with curcumin and bcsR, can be potentially effective, multifunctional targeted approach for lung cancer therapy. Graphical Abstract

Abstract Background Curcumin (CUR) is a natural polyphenol and one of the key phytoconstituents found in the rhizomes of Curcuma Longa. It exhibits various pharmacological properties, encompassing antioxidant, anticancer effects, antiseptic, and anti-inflammatory, among several others. A significant drawback of using CUR is its limited bioavailability, which primarily depends on gut microorganisms responsible for converting it into its bioavailable form. Therefore, the contemporary study intended to formulate a novel PLAROsomal vesicular delivery of CUR, i.e., CUR-PLAROsomes employing a design of experiments approach to examine the influence of various process parameters, such as particle size and drug percentage release. Result The prepared CUR-PLAROsomes were characterized for their physicochemical properties using various hyphenated tools. The CUR-PLAROsomes exhibited sizes ranging from 40 to 300 nm, and the optimized batch demonstrated a drug entrapment of 86.38 ± 0.22%. In-vitro anticancer studies were conducted using human colorectal adenocarcinoma cells (COLO320DM) and human breast adenocarcinoma (MCF-7). CUR-PLAROsomes exhibited significant in-vivo anti-inflammatory potential against carrageenan-induced paw edema. CUR-PLAROsomes were more potent against COLO320DM and MCF-7 cell lines, even at lower concentrations, than pure CUR. Conclusion Furthermore, based on the observations, it exhibits potential as an anti-inflammatory agent, suggesting that PLAROsomes are an effective vesicular drug delivery system. Highlights Newly introduced PLARosome is a next generation of Liposomes which have gain popularity owing to its better adaptability to overcome leakage problem of vesicular drug delivery system. This is the pioneer attempt to prepare Curcumin-loaded PLARosome as an anti-cancer and anti-inflammatory activity. Nano size of the PLAROsomes may contribute to enhance the efficacy of Curcumin as a target specific drug delivery system. Site specific delivery of phytoconstituents is possible by use of PLAROsomes as a novel drug delivery system. Graphical abstract

Abstract Background As the leading form of non-melanoma skin cancer, basal cell carcinoma (BCC) presents a considerable challenge to healthcare systems, owing to its widespread occurrence. Current treatment options, such as surgical excision, cryotherapy, and localized therapies like imiquimod or 5-fluorouracil, face challenges, especially in designing drug delivery systems that provide prolonged therapeutic effects. This study aims to develop bio-composite polymeric films for localized drug delivery using natural polymers, lignin, and chitosan, to enhance the delivery of the TLR7 agonist imiquimod for BCC treatment. Results The optimized biofilms were prepared by adjusting the polymer ratio and drying techniques to achieve a balanced composition for localized imiquimod delivery. FTIR and DSC characterization confirmed successful drug incorporation into the biofilms, while microscopic studies revealed the biofilms homogeneity and fibrous nature. Drug release studies demonstrated pH-dependent kinetics, with higher release rates at neutral pH. The biofilms exhibited slow and sustained drug release, promising prolonged therapeutic effects. Additionally, the biofilms were non-hemolytic, showed significant antioxidant activity, and demonstrated selective cytotoxicity against B16–F10 mouse skin melanoma cells. Conclusions This study suggests that lignin-chitosan-based imiquimod-loaded biofilms hold potential as an effective topical treatment for BCC. The biofilm’s ability to provide sustained drug release, along with their biocompatibility and selective cytotoxicity, indicates a promising approach to enhancing BCC therapy. Graphical abstract

Abstract Background Quercetin has well-proven anticancer potential through various mechanisms, but its applications in drug delivery are limited due to poor biopharmaceutical properties. The present study was aimed to formulate quercetin nanocochleates (QNC) in order to overcome these limitations. QNC formulation was fabricated by a trapping method, optimized and evaluated for various formulation aspects, in vitro cytotoxicity and pharmacokinetic parameters. Result Developed nanocochleates possess particle size and encapsulation efficiency of 205.6 ± 2.55 nm and 76.36 ± 0.88%, respectively. In vitro cytotoxicity study performed using MCF-7 cell lines revealed the comparative efficiency of QNC over pure quercetin. Total growth inhibition concentration (TGI) for pure quercetin was 96.73 μg/ml, while for QNC it was 83.29 μg/ml. Pharmacokinetic study results showed improvement in Cmax and AUC after QNC formulation with increased Tmax showing sustained release. Conclusion Overall, the developed QNC formulation markedly improved cytotoxic potential and biopharmaceutical aspects.

Abstract Background A simple suspension method, where solid formulations are disintegrated and suspended by being soaked in warm water followed by tube administration, is widely used, especially for elderly patients with dysphagia in Japanese clinical settings. However, there is insufficient information on drug stability in the simple co-suspension of multiple formulations especially including acidic or alkaline ones. The influence of occasional prolonged soakage on drug stability is also of concern. In this study, the chemical stability of typical β-lactam antibiotics, amoxicillin, and cefcapene pivoxil hydrochloride, was investigated in simple co-suspensions with magnesium oxide (MgO), which is frequently used as an alkaline laxative for the elderly. Methods Amoxicillin (capsule) or cefcapene pivoxil hydrochloride (tablet) was placed with or without MgO (tablet) in a centrifuge tube containing warm water (55 °C). The tube was allowed to stand for 10 min or 5 h at room temperature and simple suspensions were prepared. The suspensions were then treated with large amounts of solvents and neutralized using a weakly acidic cation exchange resin. The resulting solutions were analyzed by high-performance liquid chromatography. The degradation products were identified by mass spectrometry and nuclear magnetic resonance spectroscopy. Results Amoxicillin was found to be partially degraded to amoxicilloic acid and amoxicillin diketopiperazine by the co-suspension with MgO. The degree of degradation increased with the prolonged soaking. The recovery rates of cefcapene pivoxil decreased due to the poor solubility in the co-suspensions with MgO and no degradation product of the drug was observed. Conclusions Amoxicillin and MgO should be independently suspended because of the chemical instability of amoxicillin. This study has also indicated there is a degradation risk after prolonged soaking. It should be noted that the poor water solubility of cefcapene pivoxil under alkaline conditions may affect the absorption process as well as tube passability.

Abstract Background Pain and inflammation are the major medical condition commonly addressed with traditional remedies. Acacia seyal is a traditional herb widely used in Ethiopian folk medicine for pain management. However, its effectiveness has yet to be validated through scientific or experimental research. Therefore, the current study aims at evaluating the in vivo analgesic and anti-inflammatory effects of 80% methanolic stem bark extract of Acacia seyal in rodent models. Methods After successful extractions of the stem barks of Acacia seyal with 80% methanol, the pain relieving effects of 100, 200 and 400 mg/kg extract were evaluated using acetic acid-induced writhing test and hot plate method whereas the anti-inflammatory profile was determined by carrageenan induced paw-edema model and cotton pellet induced granuloma technique. Results The 80% methanol Acacia seyal stem bark extract exhibited substantial (p

Abstract Background Post-stroke delirium affects between 24% and 43% of patients, and negatively impacts patient outcomes. Recently, research attention has been on preventive interventions for delirium, with melatonin receptor agonists and orexin receptor antagonists reported to be effective in preventing delirium in intensive care unit patients. However, the efficacy of these agents in preventing post-stroke delirium remain unclear. This study examined the efficacy of ramelteon, suvorexant, and lemborexant in preventing post-stroke delirium symptoms in patients with stroke. Methods A retrospective survey of medical records was conducted for patients with stroke aged > 75 years at Kyoto University Hospital from October 2021 to March 2023. Patients who received ramelteon, suvorexant, or lemborexant on admission and the following day were classified into the consecutive administration group, whereas those who did not were classified into the non-consecutive administration group. The primary outcome was an increase in the number of positive items in the delirium screening tool over 7 days. Results Of the 104 patients, 33 and 71 were in the consecutive and non-consecutive administration groups, respectively. Fewer patients in the consecutive administration group had an increase in the number of positive items than in the other group (6% vs. 21%). Patients in the consecutive administration group significantly less often had an increase in the number of positive items in the delirium screening tool (P = 0.05; hazard ratio, 0.27; 95% confidence interval, 0.10–0.75). Conclusions This study revealed that early administration of a melatonin receptor agonist or orexin receptor antagonists may effectively prevent post-stroke delirium in older patients.

The aim of the study is to analyze reports of adverse drug reactions published in the scientific literature occurring during and after the use of kinase inhibitors for the treatment of rheumatologic diseases to determine their type, frequency, and severity. The search was conducted in the MEDLINE and PubMed databases from January 2005 to May 2022. We found a total of 291 publications, from which we selected suitable ones for data extraction. We conducted descriptive and variation analyses as the main statistical analyses. We determined mean values, standard deviation, minimum, maximum, and 95% confidence intervals. The PICOS tool was used to evaluate the results. The analyzed population includes patients with rheumatologic and oncologic diseases. There is a significant interest in the drug safety of kinase inhibitors, as they represent a rapidly evolving and reliable pharmacological class. Clarifying the safety profile of their representatives remains important. In-depth review of full-text publications shows that the high frequency of reported serious ADRs is rather due to increased interest in reporting and publishing these cases than to their high frequency of occurrence.

This study presents the computational prediction of acute toxicity for new derivatives of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenols and their alkylated analogues. The aim of the work was to evaluate the impact of structural changes, particularly alkylation and chain length extension, on the toxicity levels of new derivatives of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenols and their alkylated analogues. Materials and methods. QSAR methodologies were used to predict toxicity, allowing the evaluation of toxicological properties based on molecular descriptors. Toxicity modeling was performed using computer software, enabling the estimation of toxicity without the need for in vivo experimental studies. Results. The results showed, that alkylation of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenol derivatives does not lead to a significant toxicity reduction. Moreover, an increase in toxicity was observed with the prolongation of the carbon chain in the synthesized compounds. It was also found, that acid derivatives, particularly 2,2’-(((5-hydroxy-1,3-phenylene)bis(4-R-4H-1,2,4-triazol-5,3-diyl))bis(sulfanyl))diacetate acids and 3,3’-((((5-hydroxy-1,3-phenylene)bis(4-R-4H-1,2,4-triazol-5,3-diyl))bis(sulfanyl))bis(methylene))dibenzoyl acids, exhibit toxicity ranging from 521.9 mg/kg to 2232.2 mg/kg, corresponding to toxicity class IV (low toxicity) on the OECD scale. It was found, that molecular structure and hydrophobic properties play a crucial role in determining compound toxicity. This study helps to establish a structure-toxicity relationship and to optimize compound structures for reduced toxicity. Conclusions. These results provide a foundation for further development of potential drug candidates with predicted toxicological properties.

The development of new drug-like molecules based on 7-R-8-hydrazine derivatives of 1,3-dimethylxanthine is promising in view of the known pharmacological effect of theophylline and functional hydrazine derivatives. In silico methods make it possible to rationalize the synthesis and reduce the number of chemical compounds at the stage of virtual screening by eliminating potentially ineffective molecules. The aim of the work was to carry out а virtual design and predictive evaluation of pharmacological activity of new 7-alkyl-8-hydrazine derivatives of 1,3-dimethylxanthine by in silico methods. Materials and methods. To perform in silico prediction of the pharmacological potential of several new 7-alkyl-8-hydrazine derivatives of 1,3-dimethylxanthine, we used the online services. As 12 model compounds, we chose 12 derivatives of 5-(2-(1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)hydrazine)-5-phenylpentanoic acid with linear and branched alkyl substituents at the 7th position of the basic heterocycle: methyl-, ethyl-, n-propyl-, n-butyl, i-butyl, n-amyl, i-amyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl. The use of the freely available web tool SwissADME made it possible to calculate physicochemical parameters and to determine the drug-likeness properties of molecules. And other Internet platforms allowed to predict the spectrum of biological activity of the target compounds. Results. In silico analysis of the pharmacological potential of model compounds was performed. Three biological actions (peripheral vasodilator, kidney function stimulant, lipoprotein lipase inhibitor) with high Pa values are predicted for all derivatives of the series. The ADME parameters of the molecules were evaluated and their potential drug-like properties were determined. Conclusions. It was established that the extension of the alkyl substituent at the 7th position of the basic heterocycle should lead to a deterioration of the ADME parameters of the molecules, potentially reduce their oral bioavailability, but should not radically affect their biological activity profile. Compounds 1–3 and 5 are predicted to be orally bioavailable. They should be characterized by a wide spectrum of biological activity with the highest probability of vasodilator effect on peripheral vessels. In the future, it is advisable to carry out targeted synthesis of hit compounds and thorough in vitro, in vivo studies, and for compounds with violated physicochemical criteria – structural optimization of molecules in order to find a lead compound.

1,2,4-Triazole derivatives are of researchers’ significant interest due to their diverse biological properties, such as antimicrobial, anti-inflammatory, anticancer, and antioxidant activities. The integration of a 2-bromo-4-fluorophenyl fragment into the triazole structure can significantly enhance these activities. However, the evaluation of the toxicity of such compounds remains a critically important aspect for their practical application. To reduce the time and cost of experimental studies, QSAR (Quantitative Structure-Activity Relationship) methods are actively used, allowing the prediction of toxicity based on the molecular structure of compounds. Aim of the study. To assess the toxicity of new S-derivatives of 5-(2-bromo-4-fluorophenyl)-4-R-1,2,4-triazol-3-thiols using the QSAR method, specifically to predict acute toxicity parameters (LD50), and to determine the influence of different (length) radicals on the toxicity of these compounds. Materials and methods. The objects of the virtual study were derivatives of 5-(2-bromo-4-fluorophenyl)-4-ethyl-1,2,4-triazol-3-thiols. They were evaluated at the Department of Toxicological and Inorganic Chemistry of the Zaporizhzhia State Medical and Pharmaceutical University. The toxicity assessment was conducted using the nearest neighbor method via the Toxicity Estimation Software Tool (TEST). The prediction of the lethal dose (LD50) for rats was based on the structural similarity of the studied compounds with known substances, for which experimental toxicity data are available. Results. The conducted QSAR analysis demonstrated that structural changes in S-derivatives of 5-(2-bromo-4-fluorophenyl)-4-ethyl-1,2,4-triazol-3-thiols significantly affect the predicted toxicity. The primary factor influencing the changes in LD50 values is the variation of radicals at the 5th position of the triazole ring. Conclusions. The results of the study showed, that the toxicity of new S-alkyl derivatives of triazol-3-thiols depends on the type of alkyl substituent. Compounds with propyl to heptyl fragments exhibit increased toxicity, while derivatives with thiol, octyl, nonyl, and decyl residues are characterized by lower toxicity.

The aim of the work is to determine the prevalence of self-medication among young people and their attitude to it, with the further development of recommendations for pharmacists regarding the prevention of negative consequences of self-medication and the improvement of pharmaceutical assistance (educational activities) in matters of responsible self-medication. Materials and methods. The work used methods of information search, survey, critical analysis, generalization, and interpretation of results. The survey took place online from January to May 2024, using the developed questionnaire (the electronic version was created using Google Forms). A total of 207 questionnaires were received from people aged 20–25. Results. Mostly, it is difficult for young people to determine their attitude toward self-medication. During treatment, a large number of research participants use the advice of doctors and pharmacists. 75.8 % of respondents always study the instructions for the medical use of drugs before using them. Basically, young people do not increase the dose of drugs arbitrarily to speed up their recovery. Almost half of them do not change the prescribed medications by the doctor to cheaper analogs. According to the research participants, half of them consider an adequate amount of drugs in the form of two names, and this is confirmed by the fact that 83.6 % of them had cases of simultaneous administration of more than one drug. After undergoing self-treatment, 75.8 % of respondents consider it not always practical, among which 13.5 % indicate that it was necessary to consult a doctor. Conclusions. The prevalence and attitude toward self-medication among young people were studied. The main reasons for self-medication are the difficulty of getting to a doctor’s appointment and lack of time, as well as the reduction of disease symptoms after self-diagnosis and the use of drugs and preventive measures. It should be noted, that 23.2 % of young people nevertheless turned to a doctor after receiving negative manifestations of self-medication, and half of the respondents shared their experience of self-medication. The obtained information can be useful for pharmacy institutions, which can use it to create a comprehensive model of a program for the prevention of negative consequences of self-medication, especially among young people, and increase patients’ commitment to the pharmaceutical enterprise.

Aim. Тo assess the frequency of extragenital pathology, features of obstetric and gynecological history and the course of pregnancy in women with a history of reproductive loss. Materials and methods. The study was conducted on the basis of the Municipal non-profit enterprise “Maternity house No. 9” of the Zaporizhzhia City Council with the involvement of 75 pregnant women with one reproductive loss in history. The control group consisted of 30 women without a history of reproductive loss. Women who had reproductive losses were divided into 2 groups. Group I (main group) includes 38 pregnant women who registered for pregnancy and began their participation in this study after the start of a full-scale war on the territory of Ukraine. II (comparison) group included 37 women who were registered for pregnancy before the start of the full-scale war. It should be noted that 17 pregnant women (44.7 %) had the status of an internally displaced person. The average age of women in group I was 30.10 ± 5.86 years, in group II – 28.80 ± 6.07 years, and 26.50 ± 4.95 years in the control group. The anamnesis data and features of the course of gestation were studied in all patients. Management of pregnancy and childbirth of women was carried out in accordance with the current Orders of the Ministry of Health of Ukraine. Variational and statistical processing of the results was carried out using the Statistica 13 program. Results. According to the results of the study, it was established that the frequency of extragenital pathology in women with one reproductive loss was higher, compared to women who had no such experience. Diseases of the cardiovascular and urinary systems occupy a leading place in this category of women. According to obstetric and gynecological anamnesis, a significant predominance among women of I and II groups of diseases of the reproductive system, compared to women of the control group, was established. Also, in the corresponding groups, a high frequency of miscarriage was established both in the period up to 12 weeks (28.95 % in the I group, 43.2 % in the II group against 6.67 % in the control group), and in the period of 12–22 weeks (34.20 % in the I group, 29.73 % in the II group vs. 13.33 % in the control group). Conclusions. Based on the conducted analysis, a high frequency of pregnancy complications was established for pregnant women who had a history of one reproductive loss. This contingent of women also has a high frequency of extragenital and gynecological concomitant pathology. Such results make it possible to assume a connection between the presence of one reproductive loss in women in the anamnesis and gestational complications of the next pregnancy.

Type 2 diabetes is one of the most common and serious chronic diseases today, which has become a global health care problem. Type 2 diabetes accounts for about 90–95 % of all cases of diabetes and significantly affects patients’ quality life due to the development of numerous complications, such as cardiovascular diseases, chronic renal failure, retinopathy, neuropathy. Modern research in the field of diabetology pays considerable attention to the understanding of the genetic mechanisms of the pathogenesis of type 2 diabetes, which makes it possible to develop new approaches to its diagnosis and treatment. Individualization of laboratory diagnostics and treatment, which considers the genetic, metabolic and clinical characteristics of each patient, is a key direction in improving the effectiveness of the treatment of type 2 diabetes. Type 2 diabetes is a complex polygenic disease, that develops under the influence of both genetic and external factors, which requires an integrated approach to its diagnosis, treatment and prevention. Taking into account the constant increase in the prevalence of this disease, the relevance of scientific research in this area is beyond doubt. The development of new pharmacological agents, improvement of laboratory diagnostic strategies and individualization of treatment are key directions for overcoming the problem of type 2 diabetes and improving the quality of life of patients. The aim of the work: identification and analysis of genes panel, involved in glucose metabolism under the conditions of the development of experimental type 2 diabetes. Materials and methods. Analysis of the gene expression, involved in glucose metabolism was performed using the real-time reverse transcription polymerase chain reaction method CFX-96 Touch™ (Bio-Rad, USA) using the RT2Profiler™ PCR Array Rat Diabetes kit (QIAGEN, Germany). Results. Based on the results of the PCR study, the activity of the studied genes involved in glucose metabolism can be divided as follows: G6pc, Gpd1 – genes with high expression compared to the control group of animals; Ace, Acly, Foxg1, Foxp3, Gcgr, Gck, Gsk3b, Hmox1, Pygl, Snap23, Snap25 – genes with low expression compared to the control group of animals; Cebpa, Dpp4, Sell – genes in which no changes were detected in the samples in relation to the control group of animals; Ccr2, Fbp1, Gcg – genes, whose expression was not detected. Conclusions. The development of dexamethasone type 2 diabetes significantly (where ∆∆Ct

WHO indicates that the purpose of actions aimed at strengthening public health protection is to ensure conditions under which people can remain healthy, able to strengthen health and well-being, and prevent deterioration of health. However, in the basic documents, there is no place for health-preserving physical culture and health-improving competencies of a person in the system of general efforts. The aim of the work is to reveal the need and place of health-preserving physical culture and wellness competencies of a person as a condition for ensuring and spreading a high level of public health in Ukraine. Material and methods. The study was organized at the Dnipro State Academy of Physical Culture and Sports, the Ukrainian State University of Science and Technology, the National Technical University “Dnipro Polytechnic” (all in Dnipro) and the Zaporizhzhia State Medical and Pharmaceutical University. The used methods of theoretical research were: study and generalization of data from domestic and foreign official and literary sources, as well as abstraction, analysis and synthesis, induction and deduction. Results. Conceptual principles and didactic technology of physical education of a non-professional physical education (NpPhE), with an emphasis on strengthening the general cultural component of the educational component “Physical education” in higher education, aimed at eliminating existing shortcomings. Provided with pedagogical technology, NpPhE contributes to the formation of the building blocks of one’s own health. And the system of effective pedagogical mechanisms of NpPhE is significantly different from the provision of information about health, which is the subject of modern valeology. In this context, the development of conceptual directions of creative valeology is relevant, as a means of supporting a person’s creativity in a safe effect on health. Namely, the formation in institutions of higher education of the builders of their own health. Conclusions. A system of pedagogical mechanisms is proposed, which is significantly different from just providing information about human health as a benefit/harm of influences and actions, which is what valeology is focused on. This is a prerequisite for the formation and development of creative concepts of modern valeology based on the improvement of cultural and practical components of the educational component “Physical education” in the conditions of a higher education institution for specialists who take care of building their own health from specialties related to civilians. In conditions where the majority of their graduates are engaged not in physical, but intellectual work, the further implementation of approaches related to professional-applied physical training for professional activities is something that it is time to abandon.

The implementation of the National Recovery Plan of Ukraine in the field of “Health Care”, namely the restoration of the pharmaceutical sector, improving the population’s access to medicines and their proper use, taking into account the regulatory and legal field harmonized with European legislation, in the context of providing the qualified pharmaceutical care and pharmaceutical services requires application of modern approaches based on evidence-based medicine and implementation in pharmaceutical practice. Patients with cardiovascular diseases, who are provided with medication under the Reimbursement Program and prescriptions from doctors, must be accompanied by pharmaceutical care based on evidence-based medicine to ensure proper use of drugs and rational pharmacotherapy. The aim of the study was to investigate Ukrainian information and scientific databases, scientometric databases, i. e.: Embase, Web of Science, PubMed, and Cochrane Library to identify, generalize, and systematize scientific sources of medical and pharmaceutical data on providing patient-oriented pharmaceutical care to patients with coronary heart disease and predict the future vector of research on the specified topic. Results. The analysis of the main strategies of providing pharmaceutical care to patients with cardiovascular diseases, in particular, coronary heart disease in pharmaceutical practice was carried out; the most researched clusters of providing pharmaceutical care were identified; modern trends and tendencies in the provision of pharmaceutical care to patients with coronary heart disease were summarized. Conclusions. The development of providing qualified pharmaceutical care to patients with cardiovascular diseases is based on the principles of patient-oriented pharmacy and evidence-based medicine, which requires the design and implementation into the pharmaceutical practice of a sustainable conceptual model of providing patient-oriented pharmaceutical care by clinical pharmacists and pharmacists of pharmacy institutions with the expansion of the main roles, respectively the standards of Good Pharmacy Practice.

Aim. The purpose of this work is to emphasize the importance and practical benefits of pharmacogenetics in medicine, demonstrating how the integration of pharmacogenetics into clinical practice can improve treatment outcomes and enhance the safety of therapies. Pharmacogenetics is a rapidly developing branch of pharmacology that studies how genetic variation affects an individual’s response to drugs. By understanding these genetic differences, healthcare providers can tailor drug therapy to maximize efficacy and minimize adverse drug reactions. The field aims to move away from the traditional one-size-fits-all approach and instead personalize medical treatment based on a person’s genetic makeup. The ability to predict a person’s response to medication based on their genetic profile has profound implications. For example, pharmacogenetic testing can identify patients at risk for life-threatening adverse drug reactions, such as drug-induced liver injury. This proactive approach can prevent adverse events, improving patient safety and the overall quality of care. In addition, pharmacogenetics aids in the development of new drugs by identifying genetic markers associated with drug responses, optimizing the drug development process, and reducing the time and costs associated with bringing new drugs to market. Key advances in pharmacogenetics include the identification of genetic polymorphisms in enzymes, such as cytochrome P450, that affect drug metabolism, thereby influencing both safety and efficacy. Pharmacogenetic testing allows doctors to predict the best drug and dosage for a patient, improving treatment outcomes and reducing the risk of adverse drug events. Despite its potential, the integration of pharmacogenetics into clinical practice faces challenges, including a lack of reliable clinical evidence, inadequate physician education, and the need for a comprehensive health IT infrastructure to support the use of genetic data. Ethical and legal issues, such as patient privacy and the risk of genetic discrimination, also present significant obstacles. However, continued research, the development of genetic testing technologies, and interdisciplinary collaborations are paving the way for more widespread adoption of pharmacogenetics, which promises to significantly improve patient care and healthcare efficiency. Key resources such as PharmGKB, CPIC, and the NIH provide valuable information and guidance for clinicians, researchers, and students, helping bridge the gap between genetics research and clinical application. Conclusions. Pharmacogenetics represents a significant advancement in personalized medicine, offering the potential to tailor drug therapies to individual genetic profiles. Although the field has made substantial progress, challenges remain in the form of insufficient clinical evidence, implementation barriers, and ethical concerns. Continued research and collaboration among stakeholders are essential to fully realize the benefits of pharmacogenetic testing in clinical practice.

Nowadays, cancer remains one of the main causes of death worldwide. Statistical data from various literary sources indicate that more than 130,000 people in Ukraine receive this diagnosis as a sentence every year. Cancer can affect any organs of the human body and, over time, the entire organism. In 2024, the agency of the World Health Organization on cancer and the International Agency of Cancer Research published the latest statistical estimates of this pathology in a global format, where prostate cancer is among the five most common oncological pathologies and takes the fourth place. Oncological diseases are one of the priority areas of healthcare development in accordance with the Order of the Ministry of Health of Ukraine No. 1832 dated 07.10.2022 “On Approval of Priority Areas of Healthcare Development for 2023–2025”. It was this fact that determined the choice of the direction of this research in the matter of finding information on the provision of pharmaceutical care, namely the use of a drug – a rectal suppository for the treatment of prostate cancer. The aim of the work is to carry out a bibliometric analysis and further generalize the data of the scientific literature to study the prognostic value and features of the prescription of suppositories in the treatment of prostate cancer. Materials and methods. The data search was conducted in the PubMed electronic database using the following key terms: “prostate cancer and suppositories”, “prostate cancer”. To monitor and analyze international scientific research, with the help of visualization tools and modern SciVal citation metrics using the online platform, bibliometric analysis can be performed. Using the VOSviewer functional program, bibliometric networks were constructed and visualized. Results. A map of the relationships between the most used keywords on the topics of “prostate cancer” and “prostate cancer and suppositories”, grouped into clusters for the period from 1986 to 2024, was built. The clustering of the most used keywords on the subject of “prostate cancer” for the specified period is summarized. According to the bibliographic analysis, interest in the above topic was highest in 2014 and 2021. Conclusions. According to the bibliographic analysis, the interest in the subject of the patients’ treatment with prostate cancer disease continues to grow from 1998 up to the present. The analysis of publication activity using the visualization tool of bibliometric networks VOSviewer for the period from 2014 to 2024 for the key words “prostate cancer” has shown the presence of 14 clusters. The largest cluster is devoted to modern methods of prostate cancer treatment, studies of gene rearrangement, target therapy, carcinogenesis.

Betulinic acid (BA) is a natural pentacyclic triterpenoid with significant pharmaceutical potential. We found that converting BA into amino acid ethyl ester salts alters its cytotoxic effect on colorectal adenocarcinoma cells (HT-29). Among these salts, the estimated half-maximal inhibitory concentration (IC50) at 72 h varies by up to fifteenfold. The proline ethyl ester [ProOEt] salt, the most active compound, exhibited an IC50 value of 3.8 µM, which is 4.8 times lower than that of the parent BA. We observed that exposure to BA or [ProOEt][BA] induced apoptosis in HT-29 cells. Additionally, the proline-based salt led to a higher level of IL1B gene expression in PBMCs at a lower stimulation concentration.

Abstract Background Cancer is one of the leading causes of death worldwide, with breast and cervical cancers being the most common among women. Over 100,000 new cases of breast cancer and 510,000 new cases of cervical cancer are diagnosed annually. This study aimed to develop and evaluate an eco-friendly, low-cost method to synthesize silver nanoparticles using Hylocereus undatus (dragon fruit) peel extract for their anticancer activity. Results Silver nanoparticles loaded with Hylocereus undatus fruit peel extract were successfully developed by a green synthesis technique and were optimized by UV–vis spectroscopy. The nanoparticles had an average size of 71.66 nm, a polydispersity index of 0.3754, and a zeta potential of − 38.52, with a spherical shape and 79.5% silver content. Their maximum absorbance was at 448 nm. Further, in vitro anticancer activity via MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay was evaluated and the synthesized nanoparticles displayed IC50 values at 23.51 µg/ml and 23.66 µg/ml against Hela and MDA MB 231 cell lines, respectively. Cytocompatibility studies showed high cell viability (≥ 95%) in L929 mouse fibroblast cells, indicating low toxicity. In silico analyses, including network pharmacology and molecular docking, identified kaempferol and quercetin as key anticancer compounds, with epidermal growth factor receptor (EGFR) (PDB ID: IM17) being the most significant protein target. Docking studies performed by using the Glide module of Schrodinger’s software displayed that kaempferol and quercetin had higher binding affinities for EGFR as compared to the standard drug erlotinib, with MET 769 being a crucial binding site. Conclusion Thus, the outcomes suggest that synthesized silver nanoparticles loaded with Hylocereus undatus fruit peel extract could be a potential and promising drug carrier aiding in cancer treatment.

Abstract Background Conventional therapies in cancer treatment face challenges including drug resistance, lack of specificity, and severe adverse reactions. This study explores the potential of liposomal transdermal delivery systems as an alternative to current therapies with improved BA and PK. The objective of the study was to formulate gefitinib liposomes by thin film hydration technique (TFH) using lipoid S100. A central composite design (CCD) was used to develop and optimize GEF-LIP-TDDs and to analyze the optimum concentrations of the selected variables (phospholipid, cholesterol) in liposomal formation. The model fitting was performed using Design-Expert (Stat-Ease, Ver 13). The GEF liposomes were evaluated for %EE, mean particle size and PDI. The optimized liposomes were fabricated as a transdermal patch by mercury substrate method and evaluated for %drug content, in vitro diffusion, in vivo biodistribution (PK and BA), and skin irritation studies in female Albino Wistar rats. The stability of the optimized transdermal patch was also assessed for 3 months. Results The CCD model was significant with F-value of 37.97, P-value of 0.0500 and R 2 of 0.9644. The average vesicle size, PDI, and ZP of GEF-LIPs (F1–F13) were found to be between 112.8 to 373.7 nm, 0.186 to 0.510 and − 3.69 to − 82.2 mV, respectively. F3-GEF-LIP exhibited a mean vesicle size of 96.07 nm, ZP of − 46.06 mV, and a PDI of 0.423. F3-GEF-LIP demonstrated exceptional %EE (97.79) and sustained release effect (%CDR, 83.32) following a diffusion-controlled mechanism. TEM images confirmed liposomes of multivesicular type (MVV,

Abstract Background Cachexia, a loss of appetite and body weight as a result of systemic inflammation, considered one of the unavoidable side effects of radiation therapy. Controlling ghrelin (Ghr) levels could assist in alleviating this condition by improving appetite, promoting energy storage, and reducing cytokines’ generation. This study aimed to explore the effect of Biochanin A (BCA), a natural bioactive isoflavone, in alleviating radiation-cachexic syndrome. Results Molecular docking study of BCA demonstrated strong fitting with more binding interactions than megestrol acetate (MA), a commonly prescribed medication for cachexia, into Ghr active binding site. Accordingly, irradiated rats were treated with BCA or MA, with body weight monitoring. Force swimming test (FST) was carried out followed by gastrocnemius muscle weighting and histological examination. Biochemical assay of Ghr, TNF-α, insulin growth factor-1 (IGF-1), myostatin (Mst), lactate dehydrogenase (LDH), and brain serotonin (5-HT) level, were carried in order to estimate the possible action pathway of BCA. Results showed that BCA improved weight gain and histological muscle bundle arrangement. Although, BCA and MA significantly reduced serum TNF-α by 25.6% and 24.2%, respectively, only BCA maintained normal IGF-1and Mst levels, whose balance is necessary to avoid skeletal muscle loss, the main mark of cachexia. Moreover, BCA showed tissue injury mitigation with normal energy expenditure by significantly suppressing LDH (20.5%) and maintaining normal 5-HT level. Conclusion By preserving the appropriate IGF-1 and MST metabolic balance and keeping muscle homeostasis, BCA, with its high Ghr binding interaction and anti-inflammatory properties, could have an impact on radiation cachectic syndrome.

Abstract Background Vildagliptin (VLG), an antidiabetic agent, presents a potential solution to this widespread affliction. It exhibits notable attributes, such as a high solubility and a shorter elimination half-life. The current study uses a microreactor to fabricate sustained-release VLG-encapsulated cross-linked chitosan–dextran sulfate nanoparticles (VLG-CDNPs). The fabrication was systematically optimized using the design of experiment approach. Results The optimized VLG-CDNPs had an average particle size of 217.4 ± 12.3 nm and an encapsulation efficiency of 78.25 ± 3.0%. Scanning electron microscopy revealed that the nanoparticles had a smooth spherical shape. Spray drying was used for drying, and the reconstitution ability was close to ideal (~ 1.33). In vitro studies revealed sustained VLG release over 12 h, with ~ 58% in acidic and ~ 83% in basic conditions. Cell viability remained at 80% even at 100 μg/mL, and glucose uptake in L6 cells was significantly enhanced with VLG-CDNPs (78.34%) compared to pure VLG (60.91%). VLG-CDNPs also showed moderate inhibitory activity against α-amylase (41.57%) and α-glucosidase (63.48%) compared to pure VLG, which had higher inhibition levels. Conclusion The study’s outcome suggested that the optimized VLG-CDNPs may serve as an effective and promising nanoformulation for managing diabetes mellitus.

Abstract Background Diabetes mellitus affects millions globally, necessitating effective management strategies. Glenmark Pharmaceutical Limited introduced a fixed-dose combination of teneligliptin and dapagliflozin in 2022 to address this need. However, existing methods for their simultaneous detection are limited, lacking forced degradation studies essential for assessing drug stability. Results A stability-indicating RP-HPLC method was developed for the simultaneous determination of dapagliflozin and teneligliptin in pharmaceutical formulations. The separation was efficiently achieved employing a Zorbax Eclipse Plus C18 column (150 mm × 4.6 mm, 5 µm). The mobile phase comprised a mixture of 10 mM ammonium acetate buffer in water, methanol, and acetonitrile in a suitable proportion and delivered at a flow rate of 0.6 mL/min. Detection of the isocratic eluents was performed at 224 nm using a photodiode array (PDA) detector. Validation against various stress conditions, as per ICH guidelines, revealed significant degradation of teneligliptin primarily under acidic, basic, and oxidative stress. Moreover, liquid chromatography tandem mass spectrometry (LC-MS/MS)-based characterization was conducted for the primary degradation products of teneligliptin generated under acidic, basic, and oxidative conditions. Conclusions The developed RP-HPLC method with a stability-indicating approach provides an efficient means for the simultaneous determination of dapagliflozin and teneligliptin in pharmaceutical formulations. The significant degradation was observed under various stress conditions and also successfully separated the degradation products by this method. The proposed method directly applied for the characterization of degradation products and based on LC-MS/MS data the structure of degradation products was generated and also degradation pathways under various stress conditions were predicted. The proposed method ensured accurate and precise results in quality control process in pharmaceutical industry, and adherence to ICH validation guidelines affirms its reliability in assessing the stability of these compounds.

Abstract Background Acute coronary syndrome (ACS) patients are vulnerable to anxiety and depression. This study aimed to assess the mental health burden among Egyptian ACS patients by assessing the prevalence and associates of these conditions. This study enrolled 212 patients who underwent coronary angiogram. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Demographic, psychosocial, and clinical data were collected. Univariate and multivariate logistic regression analyses identified factors associated with anxiety and depression. Results The mean age of the participants was 54.1 years, and 80.7% were males. More than half (58.1%) exhibited anxiety, depression, or both, with depression being more prevalent than anxiety (48.1% vs 38.2%). Past major depressive disorder was strongly correlated with both anxiety and depression. Higher anxiety scores increased the odds of depression (OR = 1.234, p

Abstract Background The risks of heart disease, resistance of insulin, and diabetes mellitus type II are increased in individuals diagnosed with metabolic syndrome. Furthermore, there is an increase in the vascular and neurological effects. This study aimed to assess the isolated independent impact of hepatitis C virus (HCV) on metabolic syndrome, excluding obesity and diabetes mellitus as common risks, this impact was assessed using the metabolic syndrome Severity Z-score (MetS Z-Score) which was initially designed to assess metabolic disease severity itself. Fifty-one HCV patients non-obese and non-diabetic who visited the Tropical Medicine Department from July 2023 to June 2024 were included in our prospective cross sectional study. Results After calculation of MetS Z-Score, strong correlations were observed between MetS Z-score and the following data: HDL, fasting insulin, fasting blood sugar, HOMA-IR and hypertension (P value