Enzimski i lipidni markeri u proceni rizika za nastanak kardiovaskularnih bolesti kod žena u menopauzi

Postmenopausal women are at an increased risk of cardiovascular disease (CVD), the leading cause of death worldwide, compared with younger women. Gamma-glutamyl transferase (GGT) and high-density lipoprotein cholesterol (HDL-c) are linked with oxidative stress, inflammation, insulin resistance, and CVD risk factors. However, there have been no studies that examined the relationship between GGT/HDL-c and CVD exclusively in women who are not of reproductive age. Therefore, we aimed to examine this potential relationship in a cohort of CVD- free postmenopausal women. A total of 150 disease-free postmenopausal women were consecutively included. CVD risk was defined according to high sensitivity C-reactive protein (hsCRP) concentration (hsCRP < 1 mg/L defines low risk and hsCRP ≥ 1 mg/L defines intermediate and high risk). The GGT/HDL-c was independently associated with intermediate and high CVD risk in postmenopausal women. As this enzyme/lipid index increased by 1 unit, the probability of intermediate and high CVD risk rose by 10.3% (OR = 1.103, p = 0.024). The GGT/HDL-c ratio was independently associated with higher CVD risk, as measured with hsCRP in postmenopausal women. This cost-effective, easily measured, and widely available index could be used in everyday clinical practice for estimating CVD risk in postmenopausal women.Žene u postmenopauzi su pod povećanim rizikom od kardiovaskularnih bolesti (KVB), vodećeg uzroka smrti širom sveta, u poređenju sa mlađim ženama. Gama-glutamil transferaza (GGT) i koncentracija holesterola u lipoproteinima visoke gustine (HDL-c) povezani su sa oksidativnim stresom, upalom, insulinskom rezistencijom i faktorima rizika za KVB. Međutim, ne postoje studije koje su ispitivale odnos između GGT/HDL-c i KVB isključivo kod žena koje nisu u reproduktivnom dobu. Stoga smo imali za cilj da ispitamo pomenuti potencijalni odnos u kohorti žena u postmenopauzi bez KVB. Ukupno je uključeno 150 zdravih žena u postmenopauzi. Rizik od KVB je definisan prema koncentraciji visokosenzitivnog C-reaktivnog proteina (hsCRP) (hsCRP < 1 mg/L definiše nizak rizik, a hsCRP ≥ 1 mg/L definiše srednji i visoki rizik). GGT/HDL-c je bio nezavisno povezan sa srednjim i visokim rizikom od KVB kod žena u postmenopauzi. S povećanjem ovog enzimskog/lipidnog indeksa za 1 jedinicu, verovatnoća srednjeg i visokog rizika od KVB porasla je za 10,3% (OR = 1,103, p = 0,024). Odnos GGT/HDL- c je nezavisno povezan sa većim rizikom od KVB, merenim pomoću hsCRP kod žena u postmenopauzi. Ovaj isplativ, lako merljiv i široko dostupan indeks mogao bi se koristiti u svakodnevnoj kliničkoj praksi za procenu rizika od KVB kod žena u postmenopauzi

Comparison of Drug-Related Problems Identified During a Pharmaceutical Care Model and Physician Consultations in the Geriatric Department

Background/Purpose: The study aimed to identify common drug-related problems (DRP), their causes and pharmacists' interventions during the pharmaceutical care (PC) model and physician consultations, and to explore the gap between physicians and pharmacists to achieve a better understanding and to provide better cooperation. Methods: We conducted a single-center prospective study at the geriatric department of a tertiary academic hospital. A PC model was implemented and defined a list of pharmacy services, high-risk patients and medications. Data were collected during pharmacist's medication reviews according to the PC model and physician consultations. DRPs, causes and interventions frequency during PC model and physician consultations were compared. Results: Pharmacists identified 197 DRPs during the PC model with primarily adverse drug events (possibly) occurring, followed by untreated indication and unnecessary drug treatment. In line with that, more than half of pharmacists’ interventions were initiation or discontinuation of the drugs, followed by dosage changes. During 107 physician consultations, the most reported DRP was treatement efficacy, which demanded drug or dosage changes. Antibiotics were the top medicines related to DRPs during the PC model and physician consultations. The level of acceptance of pharmacists’ interventions was higher for physician consultations (98.1%) compared to the PC model (68.5%). Conclusion: Physicians consulted pharmacists more on questions related to treatment effectiveness, while pharmacists paid attention to medication safety. The presented results might help physicians better understand the principles of pharmacy care services and guide pharmacists during their daily practice, achieve better cooperation in multidisciplinary teams, and improve the quality of patient care

Expression Analysis of Circulating miR-21, miR-34a and miR-122 and Redox Status Markers in Metabolic Dysfunction-Associated Steatotic Liver Disease Patients with and Without Type 2 Diabetes

Metabolic dysfunction-associated steatotic liver disease (MASLD), a hepatic form of metabolic syndrome, often co-occurs with type 2 diabetes (T2D) and now affects approximately 30% of the global population. MASLD encompasses conditions from simple steatosis to metabolic dysfunction-associated steatohepatitis, with oxidative stress (OS) driving progression through inflammation. This study analyzes the expression levels of circulating miRNAs and redox status markers in MASLD patients with and without T2D, exploring their potential as disease biomarkers. The expressions of miR-21, miR-34a, and miR-122 were analyzed in the platelet-poor plasma of 147 participants, divided into three groups: MASLD + T2D (48), MASLD (50), and a control group (49). Total oxidant status (TOS), total antioxidant status (TAS), ischemia-modified albumin (IMA), and superoxide anion radical (O2•−) were measured in serum and plasma. Logistic regression showed that miR-21, miR-34a, TOS, TAS, O2•−, and IMA were positive predictors of MASLD, while miR-21 and TAS were negative predictors of T2D in MASLD. Although miR-122 did not show a significant association with either condition, in combination with miR-34a and other markers such as lipid status and liver enzymes, a new significant predictor of MASLD was identified. Circulating miRNAs in combination with redox status markers, lipid status and liver enzymes show potential as MASLD biomarkers

Development and validation of a method for the separation and determination of the Z-isomer and N-demethyltamoxifen by thin-layer chromatography

Tamoxifen is a nonsteroidal selective estrogen receptor modulator (SERM), meaning that it acts as an anti-estrogen at estrogen receptors in certain tissues (breast tissue), while acting as an estrogen in other tissues (bone tissue and endometrium). The aim of this work was to establish thin-layer chromatography (TLC) conditions for the separation of Z-isomer of tamoxifen from its impurity F (N-demethyltamoxifen) and to validate the TLC method for the assay determination of impurity F in dosage forms. The method was validated according to the International Council for Harmonisation (ICH) Q2(R2) guidelines. Samples were spotted onto the TLC silica gel G F254 plate and developed in the saturated twin-trough chamber. The selected mobile phase was toluene‒cyclohexane‒triethylamine (65:25:20, V/V). The migration distances (28 mm and 64 mm for N-demethyltamoxifen and tamoxifen, respectively) with low relative standard deviation (RSD) values (2.59%) showed satisfactory reproducibility of the chromatographic system. The TLC Scanner was used for direct evaluation of the chromatograms in reflectance/absorbance mode. The calibration curves were generated (r = 0.998). The precision and detection limits as well as the recovery values (99.16‒101.02%) were validated and found to be satisfactory. On the basis of these results, it can be concluded that the developed TLC method is a rapid and efficient method for testing the purity of tamoxifen in bulk and pharmaceutical dosage forms

Assessing potentially inappropriate medication use among older adults in Central and Eastern Europe

Objective: The aim of this study was to examine the prevalence of potentially inappropriate medication (PIM) use and its associated risk factors in community-dwelling older adults from five Central and Eastern European (CEE) countries. Materials and methods: This secondary analysis of a cross-sectional survey, which was part of the Horizon 2020 EuroAgeism ESR7 project, was conducted between February 2019 and March 2020 in Bulgaria, Croatia, Czechia, Estonia, and Serbia. We enrolled older adults aged ≥65 years who visited community pharmacies to acquire medications. The prevalence of PIM use was determined by applying all 282 criteria from the EU(7)-PIM list. Risk and protective factors for PIM use were evaluated using multiple logistic regression. R software version 4.3.2 was used in statistical analysis. Results: Most of the 2,155 participants were women (63.3%) and aged 65–74 years (64.8%). The overall PIM prevalence was 56.0% (95% confidence interval 53.8%–58.1%), ranging from 29.5% in Czechia to 70.0% in Croatia. The most commonly used PIMs were benzodiazepines (16.7% of all PIMs), followed by nonsteroidal anti-inflammatory drugs (14.3%), and proton pump inhibitors taken for more than 8 weeks (14.1%). Multiple logistic regression revealed that residence, increasing comorbidity burden, and polypharmacy were significant risk factors associated with PIM use in older adults. Conclusions: Our findings demonstrate a high prevalence of PIM use among older patients from CEE countries and considerable cross-country differences, underscoring the need to improve medication prescribing for older adults to improve healthcare quality and patient outcomes

Anatomical characterization of the aerial parts of Capsella bursa-pastoris (L.) Medik (Brassicaceae)

Contemporary studies on the composition and biological activity of the aerial parts of Capsella bursa-pastoris (Brassicaceae) support the traditional confidence in this medicinal plant, widely used in folk medicine, particularly for the treatment of various types of bleeding. Bursae pastoris herba is listed within Community herbal monographs of European medicines agency (EMA), but it is not official in any modern Pharmacopoeia. Due to the increasing interest in this species, commonly harvested from wild populations, there is a growing need for the evaluation of its pharmacognostic attributes as a medicinal raw material. The aim of this study was to contribute to the characterization of C. bursa-pastoris herb by conducting a comparative anatomical analysis of five samples collected from natural habitats in Serbia. Anatomical features of stems, leaves, and fruits were examined in detail. Among the most prominent microanatomical traits, potentially useful as diagnostic markers of the herbal drug, are branched unicellular trichomes covered with warty cuticular outgrowths on the surface of stems and leaves, a papillose epidermis of the petals, and a striated endocarp of the silicle

Immunomodulatory effects of Pelargonium sidoides extract (EPs7630) in the treatment of acute rhinosinusitis

In this short narrative review, we would like to discuss the immunomodulatory effects of South African geranium (Pelargonium sidoides) root extract EPs7630 in treating acute rhinosinusitis. The plant has been used for centuries to treat respiratory tract inflammation, such as sinusitis, pharyngitis, and bronchitis. South African geranium is rich in polyphenols, flavonoids, tannins, diterpenes, and proanthocyanidins, but the main constituent is a type of coumarin called’umckalin’ (6–hydroxy–5,5–dimethoxy–coumarin). The substance is standardized as an aqueous-ethanolic extract from the root of this plant under the code name EPs7630. The article presents the results of in vitro and in vivo studies of administering this herbal drug in acute viral, post-viral, and bacterial rhinosinusitis. The focus is on the immunomodulatory effects of EPs7630 during the therapy of this acute inflammation of the nasal mucosa. According to the results of some studies, EPs7630 stimulates monocyte-dependent activity and inhibits neutrophil-dependent chemokine activity. However, given the small number of studies, the level of evidence is low, implying the need for new research. Particular attention should be paid to the effect of EPs7630 on bradykinin, the mediator that triggers most inflammatory processes in acute rhinosinusitis

Sustainable Analysis of Diclofenac Salts: A Chemometric Approach to Mixed-Mode Liquid Chromatography With Charged Aerosol Detection

Active pharmaceutical ingredients (APIs) are often used in salt form because of enhanced bioavailability. This study aims to propose a new environmentally friendly method for the analysis of raw diclofenac substance, achieving simultaneous analysis of diclofenac and its counterions (Na+ and K+), utilizing mixed-mode liquid chromatography (MMLC) and charged aerosol detector (CAD). To optimize the critical method characteristic—the mobile phase composition—a 32 full factorial design of experiments and multiobjective decision making using Derringer's desirability function were employed. Two optimized methods with acceptable run times and satisfactory peak separation were developed. The methods compared the use of acetonitrile (ACN) and acetone (ACE) in terms of method sustainability. The mobile phase composition in the first method (MMLC–ACN) was 40% ACN and 60% ammonium acetate buffer (48.00 mM, pH 4.82), whereas in the second, improved method (MMLC–ACE), it was 50% ACE and 50% ammonium acetate buffer (40.00 mM, pH 4.62). The eco-friendliness of the developed methods was assessed using the GAPI, the Analytical GREEnness (AGREE) score, and the Greenness Index. The method with ACE as the mobile phase modifier demonstrated a better environmental profile, achieving an AGREE score of 0.69, compared to the ACN-based method, which scored 0.60. Method performance characteristics of the MMLC–ACE method used for the quantitative analysis of diclofenac salt raw materials were evaluated according to ICH Q2(R2) guidelines: precision—repeatability (RSD from 1.07% to 2.41% and recovery >97%), selectivity between critical peak pair (αNa/K > 1) and obtained linear response within concentration range of 50%–150% (r > 0.99)

Constitutive androstane receptor, liver pathophysiology and chemical contaminants: current evidence and perspectives

Introduction: The Constitutive Androstane Receptor (CAR) (NR1I3), a pivotal member of the xenosensor family, plays a key role in the hepatic detoxification of xenobiotic and endobiotic chemicals through the induction of the expression of drug-metabolizing enzymes and transporters. CAR’s involvement extends beyond detoxification, influencing gluconeogenesis, lipogenesis, bile acid regulation, and cellular processes such as proliferation, tissue regeneration, and carcinogenesis. This review explores CAR regulation by various factors, highlighting its role in mediating metabolic changes induced by environmental contaminants. Methods: A literature search was conducted to identify all articles on the PubMed website in which the CAR-contaminant and CAR-hepatic steatosis relationship is analyzed in both in vitro and in vivo models. Results: Numerous contaminants, such as perfluorooctanoic acid (PFOA), Zearalenone mycotoxin, PCB, triazole fungicide propiconazole can activate hepatic nuclear receptors contributing to the development of steatosis through increased de novo lipogenesis, decreased fatty acid oxidation, increased hepatic lipid uptake, and decreased gluconeogenesis. Indirect CAR activation pathways, particularly involving PFOA, are discussed in the context of PPARα-independent mechanisms leading to hepatotoxicity, including hepatocellular hypertrophy and necrosis, and their implications in nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD). The prevalence of NAFLD, a significant component of metabolic syndrome, underscores the importance of understanding CAR’s role in its pathogenesis. Conclusions: Experimental and epidemiological data suggest that endocrine disruptors, especially pesticides, play a significant role in NAFLD’s development and progression via CAR-regulated pathways. This review advocates for the inclusion of modern toxicological risk assessment tools, such as New Approach Methodologies (NAMs), Adverse Outcome Pathways (AOPs), and Integrated Approaches to Testing and Assessment (IATA), to elucidate CAR-mediated effects and enhance regulatory frameworks

Not Just Water: Ionic Influence on the Rheology of Natural O/W Emulsions

BACKGROUND: The study investigates how different aqueous phases—purified water, two mineral waters, and one thermal mineral water—affect the physicochemical and mechanical properties of oil-in-water emulsions stabilized with two non-ionic alkyl polyglucoside (APG) emulsifiers—Montanov™68 (Cetearyl Alcohol and Cetearyl Glucoside) and Montanov™82 (Cetearyl Alcohol and Coco Glucoside). Comprehensive characterization included pH and conductivity measurements, microscopy, rheology, and texture analysis. Given the routine adjustment of topical emulsions to skin-relevant pH, rheological measurements were repeated after adjusting each formulation to pH 5.5. RESULTS: Unlike electrolyte effects typically described for ionic surfactant systems, this work demonstrates that ion identity and mineralization level of the aqueous phase significantly influence structure and mechanical properties of emulsions stabilized by non-ionic APG emulsifiers, which are generally assumed to be insensitive to electrolytes. Distinct mineral compositions produced measurable changes in viscosity, firmness, and viscoelastic behaviour, revealing that mineral waters actively modulate lamellar gel network organization. In contrast, adjusting the pH to 5.5 resulted in minor changes, confirming that aqueous ionic composition is the dominant factor shaping the final emulsion properties. CONCLUSION: These findings provide the first evidence that, in APG-stabilized emulsions, the water phase functions as an active structural component rather than an inert solvent. Different performances of structurally similar emulsifiers towards the same electrolytes profile indicate how small variations in lamellar architecture can lead to different outcomes. Consequently, the choice of mineral or thermal water can be strategically used as a formulation tool to deliberately tailor the texture, rheology, and structural organization of natural emulsions. © 2025 Society of Chemical Industry (SCI)