Dissolution of water-insoluble drugs is an important challenge in drug delivery. Adsorbing water-insoluble drugs onto nanoporous carriers such as zeolites can improve drug dissolution.  The drug molecules adsorbed in a thin layer onto nanoporous carriers are fully exposed to the solvent, enhancing the dissolution process. This presentation will give new insights into the adsorption of water-insoluble letrozole drug onto the nanoporous clinoptilolite zeolite from a nanoscale-science point of view based on experimental and theoretical considerations. Adsorption of the letrozole drug on clinoptilolite zeolite will be conducted from the colloidal dispersion state. The amount of letrozole adsorbed in a monolayer will be evidenced by thermogravimetric measurements, while optical spectroscopy techniques will reveal the interactions of the letrozole drug on the nanoporous zeolite framework. Positive adsorption energy at the letrozole-clinoptilolite interface calculated using density functional theory models suggests a small affinity for letrozole adsorption, suggesting the letrozole release is more favorable than the adsorption process. Thus, this presentation will show new possibilities in adsorption and dissolution of water-insoluble drugs.

Background/Objectives: Improper use of systemic antibiotics remains a significant concern in hospital settings, contributing to increased antimicrobial resistance and suboptimal clinical outcomes. The COVID-19 pandemic exacerbated this issue. This study aimed to evaluate long-term trends in antibiotic utilization in low-resource settings at a tertiary care teaching hospital, focusing specifically on the changes before, during, and after the COVID-19 pandemic. Methods: This retrospective observational study analyzed antibiotic utilization data from the University Clinical Centre of the Republic of Srpska over ten years (2015–2024). Antibiotic consumption was expressed in defined daily doses (DDD) per 100 bed-days, and compared across three periods: pre-COVID-19 (2015–2019), COVID-19 (2020–2022), and post-COVID-19 (2023–2024). Additionally, antibiotic use was categorized according to the WHO AWaRe classification. Results: Antibiotic utilization peaked during the COVID-19 period, with the highest rate observed in 2021 (91.5 DDD/100 bed-days), despite a decrease in hospital admissions. The most frequently used antibiotics were cephalosporins, penicillins, and metronidazole. A significant increase in the use of azithromycin, meropenem, piperacillin/tazobactam, vancomycin, and colistin was noted during the COVID-19 and post-COVID-19 periods (p < 0.05), along with a notable decline in penicillin use. Watch and Reserve antibiotic use rose significantly (p < 0.05), while Access group use fell from 67% to 49.2%. Conclusions: These findings underscore the lasting impact of the COVID-19 pandemic on antibiotic prescribing patterns and emphasize the urgent need for strengthened antimicrobial stewardship efforts to ensure rational antibiotic use and combat antimicrobial resistance.

Background: The process of prenatal hematopoiesis occurs in various anatomical locations, including the placenta. The placenta is not merely a temporary hematopoietic reservoir, but it is one of the key sites for the synthesis of hematopoietic stem cells (HSCs). This study aimed to investigate the presence, distribution, and immunoprofiles of HSCs in the human placenta during different gestational periods. Materials and Methods: Placental samples of different gestational ages (first, second, and third trimesters) were analyzed using classical hematoxylin and eosin staining and immunohistochemical staining for CD34, CD117, and CD41 markers, with HSC quantification through numerical areal density (NA). Results: Highly immunoreactive CD34 HSCs were present in placentas throughout gestation, while highly immunoreactive CD117 and CD41 HSCs were observed during the first two trimesters. In the first trimester, HSCs were found within the lumen of blood vessels and as individual cells in the mesenchyme of chorionic villi. With advancing gestation, the number of HSCs in the mesenchyme of chorionic villi increased. Conclusions: Immunoreactive CD34, CD117, and CD41 cells are present in significant proportions in various parts of the placenta throughout gestation, indicating that the placenta provides a substantial proportion of HSCs for hematopoiesis.

Introduction This study aimed to investigate the anti-inflammatory, antioxidant, and anti-apoptotic properties of ursodeoxycholic (UDCA) and chenodeoxycholic (CDCA) bile acids in a rat model of endotoxin (lipopolysaccharide, LPS)-induced acute lung injury (ALI). Methods The study included six groups of Wistar rats exposed to different pretreatments. The control and endotoxin groups were pretreated with propylene glycol, a solvent for bile acids, while the other groups received UDCA or CDCA for 10 days. On the 10th day, an endotoxin injection was given to evaluate the impact of these pretreatments. Lung tissue sections were analyzed by immunohistochemistry, targeting the pro-inflammatory marker nuclear factor kappa B (NF-κB), the anti-apoptotic marker B-cell lymphoma 2 (BCL-2), pro-apoptotic markers BCL-2-associated X protein (BAX) and caspase 3, as well as the aquaporins 1 and 5 (AQP1 and AQP5). Oxidative stress was assessed in bronchoalveolar lavage fluid (BALF). Results and discussion This study demonstrates that UDCA and CDCA can mitigate endotoxin-induced lung injury in rats. These effects are achieved through modulation of AQP1 and AQP5 expression, reduction of oxidative stress, regulation of apoptotic pathways (BAX, caspase 3, BCL-2), and attenuation of pro-inflammatory activity of NF-κB. Although the results indicate a significant association between the expression of these proteins and histopathological changes, the potential influence of additional factors cannot be excluded. These findings suggest that UDCA and CDCA provide lung protection by acting through complex mechanisms involving inflammatory, oxidative, and apoptotic pathways.

Background: Myocardial injury (MI) is characterized by an increased level of at least one cardiac troponin. Experimental MI can be induced by isoprenaline, a β-adrenergic agonist, and it can lead to heart failure (HF). Liraglutide is glucagon-like 1 peptide receptor agonist used in diabetes management, but it has anti-inflammatory and antioxidative effects, which can be beneficial in treatment of HF. The aim of this study was to investigate the effects of liraglutide on isoprenaline-induced MI and prevention of HF. Methods: Male Wistar albino rats were divided into four groups: Con—received saline the first 2 days + saline the next 7 days; Iso—isoprenaline the first 2 days + saline the next 7 days; Lir—saline the first 2 days + liraglutide the next 7 days; Iso + Lir—isoprenaline the first 2 days + liraglutide the next 7 days. On day 10, blood samples were taken for biochemical analysis and oxidative stress marker evaluation, and hearts were isolated for pathohistological analysis. Cardiac function was assessed by electrocardiography (ECG) and echocardiography (ECHO). Results: Liraglutide treatment significantly attenuated oxidative stress, repaired ECG and ECHO parameters, and mitigated myocardial morphological changes induced by isoprenaline. Conclusions: Liraglutide restores cardiac function in isoprenaline-induced HF.

The aim of this study was to determine the antidotal potential of the chlorinated oxime K870 compared to obidoxime, as a monotherapy and in combination with atropine, in paraoxon (POX)-poisoned rats. The treatment doses of oximes were chosen as 20% of their LD50 values. The protective ratio (PR) of oxime K870 with atropine was significantly higher than that of obidoxime with atropine (68.8 and 125.0, respectively). In the biochemical part of the experiment POX subcutaneously (s.c.) (0.75% LD50) was administered and followed by oxime K870 or obidoxime i.m. 1 min later. Acetylcholinesterase (AChE) activity was determined spectrophotometrically in cerebrum, cerebellum, brainstem, diaphragm, and erythrocytes. Carboxylesterase activity was determined in plasma and liver. Both oximes successfully reactivated AChE in brain (cerebrum, cerebellum, and brainstem), diaphragm and erythrocytes, but the oxime K870 performed better than obidoxime. Both oximes reactivated carboxylesterase, obidoxime better in plasma and oxime K870 better in liver. In conclusion, the oxime K870, when co-administered with atropine, is a more effective antidote than the obidoxime-atropine combination in POX-poisoned rats.

The aim of the study was to assess the seroprevalence of SARS‐CoV‐2 in the Republika Srpska, Bosnia and Herzegovina, after five waves of COVID‐19 and 1 year after introduction of vaccination to better understand the true extent of the COVID‐19 pandemic in the population of the Republika Srpska and role of vaccination in achieving herd immunity.

Psoriasis is a chronic inflammatory skin disease with relapsing nature. Estimates are that approximately 2–3% of the world’s population suffers from this disease. More severe forms of psoriasis are conditions of high inflammation, which is confirmed by the clinical picture and numerous inflammatory parameters such as C-reactive protein (CRP), cytokines and homocysteine, which vary with disease activity. The objective of this clinical study was to investigate the effect of GLP-1 receptor agonist semaglutide therapy on pro-inflammatory factors in the serum and the severity of the clinical picture of psoriasis in obese patients with type 2 diabetes mellitus (T2DM) on chronic metformin therapy. This randomized clinical study was conducted on 31 psoriatic patients with T2DM that were randomized into two groups: one that received semaglutide during the 12-week trial (n = 15), while the second was control (n = 16). The results demonstrated that the severity of the clinical picture of psoriasis, determined by the Psoriasis Area and Severity Index (PASI) score, was significantly better after the administration of semaglutide (the median baseline PASI score in patients treated with semaglutide was 21 (IQR = 19.8), while after 12 weeks of therapy the score was 10 (IQR = 6; p = 0.002). Also, the quality of life in the group of patients who received the drug, measured by the Dermatology Life Quality Index (DLQI), improved significantly after 3 months (a median baseline DLQI score in the semaglutide group was 14 (IQR = 5) at the beginning of the study, and after 12 weeks of treatment the median DLQI score was 4 (IQR = 4; p = 0.002)). The use of semaglutide led to a significant decrease in pro-inflammatory cytokines in the serum (IL6), as well as a significant decrease in CRP values (p < 0.05). A significant decrease in the body mass index (BMI) value in the semaglutide-treated group was also identified, as well as a significant decrease in the level of low-density cholesterol (LDL) (p < 0.05). In conclusion, semaglutide, based on its systemic anti-inflammatory characteristics, could contribute to the treatment of psoriatic obese patients with T2DM.

BACKGROUND Limited joint mobility is the proven risk factor for diabetic foot ulceration when present in the subtalar and first metatarsophalangeal joints. Evidence shows that a foot-related exercise program, combined with a health-promoting program, can improve the signs and symptoms of diabetic polyneuropathy, enhance gait, restore mobility in the foot and ankle joints, redistribute pressure while walking, and increase foot strength and function. As a result, these exercise programs can help mitigate the risk factors for diabetic foot ulceration. AIM To determine the effect of supervised stretching, strengthening, functional and walking exercises on joint mobility and muscle strength in patients with diabetic polyneuropathy. METHODS This was a randomized controlled trial conducted in a tertiary hospital. The study included 82 participants allocated into the intervention group (alpha-lipoic acid and exercise on 15 consecutive therapeutic days, n = 42) and control group (alpha lipoic acid only, n = 40). Muscle strength included dorsal and plantar flexors dynamometry and strength score, while range of motion included ankle, subtalar and first metatarsophalangeal joint goniometry. RESULTS Change of motion range was significantly higher in the intervention group compared to the control group regarding ankle joint on day 15 (9.9 ± 7.2 vs 0.1 ± 3.3; P = 0.006) and month 6 (2.8 ± 7.3 vs -0.9 ± 4.1; P < 0.001), subtalar joint on day 15 (7.5 ± 5.1 vs -0.25 ± 2.25; P < 0.001) and month 6 (3.9 ± 6.4 vs -0.13 ± 3.49; P < 0.001). Change in dorsal flexors was significantly higher in the intervention group compared to the control group on day 15 (2.62 ± 1.69 vs 0.10 ± 1.35; P < 0.001) and month 6 (0.66 ± 2.38 vs -0.75 ± 1.94; P = 0.004) as well as plantar flexors on day 15 (3.3 ± 1.6 vs 0.3 ± 1.5; P < 0.001) and month 6 (1.8 ± 2.2 vs -0.9 ± 2.1; P < 0.001). Muscle strength score change was significantly lower in the intervention group compared to the control group on day 15 (-1.45 ± 1.42 vs -0.03 ± 0.16; P < 0.001) and month 6 (-1.17 ± 1.53 vs 0.20 ± 0.56; P < 0.001). CONCLUSION Exercise in combination with alpha-lipoic acid can improve joint mobility, as well as strength of the foot and lower leg muscles in patients with diabetic polyneuropathy.

Background/Objectives: The importance of fixed-dose combinations (FDCs) for the treatment of hypertension is well established. However, from a stability perspective, FDCs present a challenge since the degradation of one active pharmaceutical ingredient (API) can be affected by the presence of another API. The aim of this study was to compare the degradation behaviors and evaluate the degradation kinetics of three antihypertensive drugs, perindopril tert-butylamine (PER), amlodipine besylate (AML), and indapamide (IND). Methods: The degradation processes were studied using the previously developed reverse phase high-performance liquid chromatographic (RP-HPLC) method after exposing each drug individually, as well as the combinations of two/three drugs, to different stress factors, such as light, oxidation, acidic, basic, or neutral pH values at different temperatures. Results: The results show that PER is most unstable under basic conditions and that AML displays a negative, while IND displays a positive effect, on PER stability when combined. AML is most affected by basic conditions and oxidation, and its stability is affected by both drugs positively; IND undergoes extreme photolysis, which is positively affected by AML but negatively by PER. Conclusions: Great care must be taken when formulating FDCs with these three drugs, as well as solutions or oral suspensions adjusted for geriatric or pediatric populations, since the stability of all three drugs is greatly affected by pH conditions, as well as light or oxidation factors and their interactions.