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Antiplatelet Drugs Use in Pregnancy—Review of the Current Practice and Future Implications
Get PDFWhen clinicians opt for antithrombotic therapy to manage or prevent thrombotic complications during pregnancy, it is imperative to consider the unique physiological state of the pregnant woman’s body, which can influence the pharmacokinetics of the drug, its ability to traverse the placental barrier, and its potential teratogenic effects on the fetus. While the efficacy and safety of aspirin during pregnancy have been relatively well-established through numerous clinical studies, understanding the effects of newer, more potent antiplatelet agents has primarily stemmed from individual clinical case reports necessitating immediate administration of potent antiplatelet therapy during pregnancy. This review consolidates the collective experiences of clinicians confronting novel thrombotic complications during pregnancy, often requiring the use of dual antiplatelet therapy. The utilization of potent antiplatelet therapy carries inherent risks of bleeding, posing threats to both the pregnant woman and the fetus, as well as the potential for teratogenic effects on the fetus. In the absence of official guidelines regarding the use of potent antiplatelet drugs in pregnancy, a plethora of cases have demonstrated the feasibility of preventing recurrent thrombotic complications, mitigating bleeding risks, and successfully managing pregnancies, frequently culminating in cesarean deliveries, through meticulous selection and dosing of antiplatelet medications
Quantification of oxidative stress markers in the blood sera following subacute administration of different oximes in rats
No full textOxidative stress status, as a disruption of redox homeostasis, in the blood sera of Wistar rats caused by repeated application of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, K074, and K075 were evaluated. Throughout this study, each oxime in a dose of 0.1 of LD50/kg im was given 2x/week for 4 weeks. Then, seven days after the last oximes' application, markers of lipid peroxidation (malondialdehyde, MDA), and protein oxidation (advanced oxidation protein products, AOPP), as well as the activity of antioxidant enzymes (catalase, CAT, superoxide dismutase, SOD, reduced glutathione, GSH, and oxidized glutathione, GSSG), were determined. Oxidative stress parameters, MDA and AOPP were significantly highest in the K048-, K074- and K075-treated groups (p < 0.001). The activity of CAT was significantly elevated in the obidoxime-treated group (p < 0.05), while treatment with K027, K048, and K074 induced high elevation in SOD levels (p < 0.01, p < 0.001). Interestingly, the activity of GSH in each oxime-treated group was significantly elevated. Unlike, treatment with obidoxime caused elevation in GSSG levels (p < 0.01). As a continuation of our previously published data, these results assure that applied oximes following subacute treatment ameliorated the oxidative status and further adverse systemic toxic effects in rats
Corrigendum to “Cadmium sulfide-induced toxicity in the cortex and cerebellum: In vitro and in vivo studies” [Toxicol. Rep. 7 (2020) 637–648, (S2214750019304202), (10.1016/j.toxrep.2020.04.011)]
Get PDFThe author regrets, that the manuscript made an inadvertent error in the layout of composite Fig. 10 (the corners of Fig. 10B and 10C for different experimental conditions overlapped). After investigating the causes of the error and carefully checking the source data, the error noted by the interested Reader (https://www.pubpeer.com/publications/8C7547CE40467671FA999B10747399) was corrected. The authors express their gratitude to the Reader who discovered this error. Corrected Fig. 10 is shown below. The authors would like to apologize for any inconvenience caused. DOI of original article: 10.1016/j.toxrep.2020.04.011Link to the corrected article: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/3593
COVID-19 increases mortality in hemodialysis patients: exploring links with inflammation and telomere attrition
No full textBackground and objective: An increased risk of mortality and hospitalization was consistently demonstrated in hemodialysis (HD) patients affected by pandemic coronavirus infection (COVID-19). In this study, we analyzed parameters that may impact mortality in COVID-19 HD patients, including neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP), COVID-19 disease status and telomere length in peripheral blood cells (TL). Materials and methods: A total of 130 chronic hemodialysis patients were enrolled and followed up for 18 months. Patients were categorized into groups based on their COVID-19 disease history and subsequent data about their survival status at the end of the study. Routine laboratory parameters were assessed using standard automated methods and TL was determined using the modified Cawthon method. Survival predictors were analyzed using Kaplan-Meier analysis. Results: Deceased patients (30%) were older with higher body mass index (BMI), higher levels of LDH, NLR index, CRP and lower TL and lymphocytes count compared to survivors. Kaplan-Meier survival analysis showed six parameters were significant mortality predictors in the following order of significance: COVID-19 history, 2-years cardiovascular mortality risk score, NLR, TL, CRP, LDH. Using binary logistic regression analysis Summary risk score, a combination of these six parameters revealed as the best predictor of patient’s survival in this group of parameters (log rank 25.4, p < 0.001). Conclusion: Compared to the general population, the mortality rate among HD patients persists at a higher level despite advancements in HD technology and patient care. The situation has been exacerbated by COVID-19, by significant increase in mortality rate among these patients
Extracts from Wheat, Maize, and Sunflower Waste as Natural Raw Materials for Cosmetics: Value-Added Products Reaching Sustainability Goals
Get PDFAgricultural waste is underutilized, and sometimes burning them has a negative impact on the environment and human health. This research investigates the untapped potential of extracts from maize, wheat and sunflower waste as natural materials for cutaneous, specifically, cosmetic application. The possibility of incorporating lipid and ethanol extracts from wheat, maize, and sunflower into creams was investigated together with their potential contribution to the structural and functional properties of the topical formulations. Results of the physicochemical characterization show that investigated extracts can be successfully incorporated into creams with satisfactory stability. All extracts showed a desirable safety profile and good antimicrobial activity against various microorganisms. Lipid extracts have proven to be promising structural ingredients of the oil phase, contributing to the spreadability, occlusivity, and emollient effect. Ethanol extracts influenced washability and stickiness of the formulation and could be considered as prospective ingredients in self-preserving formulations. The extracts affected the sensory properties of the creams, mainly the smell and color. These results suggest that the extracts from wheat, maize, and sunflower waste could be used as multifunctional natural ingredients for cosmetic formulations which can replace less sustainable raw materials. This also represents a valorization of waste and is in line with broader sustainability goals
Exploring serum trace element shifts: Implications for cervical intraepithelial neoplasia
No full textBackground: Cervical intraepithelial neoplasia (CIN) represents a premalignant state presumably related to perturbations in circulating levels of trace elements. Materials and methods: Employing inductively coupled plasma mass spectrometry (ICP-MS), we quantified essential and toxic trace elements in the sera of 60 women diagnosed with CIN and 60 age-matched healthy counterparts. Results: Our investigation revealed a noteworthy higher levels in serum of Mn, Zn, and Pb, as well as lower levels in Ni, Se, Rb, and Mo levels within the CIN cohort. Levels of Mn, Zn, and Pb were higher by approximately 5.5-fold, 3.0-fold, and 7.5-fold, respectively, while Mo levels exhibited an approximate 4.5-fold reduction in CIN sera compared to the control group. While the study provided valuable insights into trace element variations, it's important to note that the adult Serbian population is considered Zn-deficient, so the Zn data should be interpreted with caution. Age stratification (30–40 vs. 40–50 vs. 50–60 years), smoking status (smokers vs. nonsmokers), and CIN severity (CIN 2 vs. CIN 3) yielded no significant disparities in elemental profiles. Among the 10 proposed ratios, 5 demonstrated a significant surge in CIN sera relative to controls: Mn/Se, Mn/Mo, Zn/Se, Zn/Mo, and Se/Mo. Correlation analysis of trace element levels revealed a predominantly consistent pattern between CIN cases and healthy subjects, except for Zn and its negative correlations (antagonistic interactions) with other analyzed trace elements. Conclusion: Our findings underscore differences in serum levels of specific trace elements in CIN cases versus controls, implicating their potential involvement in the underlying pathophysiological cascades culminating in cervical neoplasms
Neuropharmacokinetic profiles of GL-II-73, a positive allosteric modulator of α5GABAA receptors, and its metabolite MP-III-022: nanoemulsion vs solution formulation comparison
No full textComparison of the blood and plasma pharmacokinetic parameters obtained after intraperitoneal administration of GL-II-73-loaded nanoemulsion and
solution formulation to the ratsRelated to poster: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/5787
Chitosan–Clay Mineral Nanocomposites with Antibacterial Activity for Biomedical Application: Advantages and Future Perspectives
No full textPolymers of natural origin, such as representatives of various polysaccharides (e.g., cellulose, dextran, hyaluronic acid, gellan gum, etc.), and their derivatives, have a long tradition in biomedical applications. Among them, the use of chitosan as a safe, biocompatible, and environmentally friendly heteropolysaccharide has been particularly intensively researched over the last two decades. The potential of using chitosan for medical purposes is reflected in its unique cationic nature, viscosity-increasing and gel-forming ability, non-toxicity in living cells, antimicrobial activity, mucoadhesiveness, biodegradability, as well as the possibility of chemical modification. The intuitive use of clay minerals in the treatment of superficial wounds has been known in traditional medicine for thousands of years. To improve efficacy and overcome the ubiquitous bacterial resistance, the beneficial properties of chitosan have been utilized for the preparation of chitosan–clay mineral bionanocomposites. The focus of this review is on composites containing chitosan with montmorillonite and halloysite as representatives of clay minerals. This review highlights the antibacterial efficacy of chitosan–clay mineral bionanocomposites in drug delivery and in the treatment of topical skin infections and wound healing. Finally, an overview of the preparation, characterization, and possible future perspectives related to the use of these advancing composites for biomedical applications is presented
Involvement of different K+ channel subtypes in hydrogen sulfide-induced vasorelaxation of human internal mammary artery
No full textBackground
Changes in K+ channel expression/function are associated with disruption of vascular reactivity in several pathological conditions, including hypertension, diabetes, and atherosclerosis. Gasotransmitters achieve part of their effects in the organism by regulating ion channels, especially K+ channels. Their involvement in hydrogen sulfide (H2S)-mediated vasorelaxation is still unclear, and data about human vessels are limited.
Objective
To determine the role of K+ channel subtypes in the vasorelaxant mechanism of H2S donor, sodium-hydrosulfide (NaHS), on isolated human internal mammary artery (HIMA).
Results
NaHS (1 × 10−6–3 × 10−3 mol/L) induced a concentration-dependent relaxation of HIMA pre-contracted by phenylephrine and high K+. Among K+ channel blockers, iberiotoxin, glibenclamide, 4-aminopyridine (4-AP), and margatoxin significantly inhibited NaHS-induced relaxation of phenylephrine-contracted HIMA (P 0.05). In the presence of nifedipine, NaHS induced partial relaxation of HIMA (P < 0.01).
Conclusion
Our results demonstrated that H2S donor, NaHS, induced concentration-dependent relaxation of isolated HIMA. Vasorelaxant mechanisms of H2S included direct or indirect opening of different K+ channel subtypes, KATP, BKCa, SKCa/IKCa, and KV (subtype KV1.3), in addition to NO pathway activation and interference with extracellular Ca2+ influx.This is the peer-reviewed version of the article: Marinko, M., Stojanović, I., Milojević, P., Nenezić, D., Kanjuh, V., Yang, Q., He, G.,& Novaković,
A.. (2024). Involvement of different K+ channel subtypes in hydrogen sulfide-induced vasorelaxation
of human internal mammary artery. in Fundamental and Clinical Pharmacology
John Wiley and Sons Inc..
[https://doi.org/10.1111/fcp.13036
Data-driven insights into the properties of liquisolid systems based on machine learning algorithms
No full textLiquisolid systems (LS) represent a formulation approach where liquid drug or its dispersion is transformed into a powder with good flowability and compactibility, leading to enhanced drug dissolution and bioavailability. Many research groups have focused on the preparation and investigation of LS, leading to a higher need for comprehensive evaluation of factors impacting LS characteristics. The aim of this work was to investigate the applicability of machine learning algorithms in the LS evaluation, using data mined from published literature, and provide an insight into critical factors governing the liquisolid system performance. The dataset was prepared using publication search engines and relevant keywords, with a total of 425 formulations included in the database. The database focused on preparation methods, formulation parameters, and liquisolid system characteristics. Subsequently, critical properties of the liquisolid system, i.e. flowability, compact hardness, and drug dissolution, were analyzed using machine learning algorithms, including Gradient Boosting, Adaptive Boosting and Random Forest. In addition to conventional preparation methods and excipients, novel technologies (fluid bed preparation, extrusion/spheronization) and materials (Neusilin®, Fujicalin®, and Syloid®) enhanced the properties of liquisolid systems. The analysis revealed that formulation factors, such as carrier and coating agent type and content, liquid phase load, model drug type and content, as well as preparation method, significantly influenced liquisolid system characteristics. The models developed exhibited high prediction accuracy when applied on test data (higher than 80 %). This indicates that the machine learning models may provide an insight into the critical attributes affecting the LS performance and may be used as a valuable tool in the development and optimization of these samples