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    The role of 3D printing in the development of dosage forms with tailored drug release

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    In recent years, there has been growing interest in the application of 3D printing technology in the production of drug delivery systems. The particular advantages of using 3D printing lie in the production of drug delivery systems with dose, appearance (size, shape, colour, etc.) and drug release pattern tailored to the characteristics of each patient. This enables more efficient therapy, improved patient compliance, reduced costs, and fewer side effects. Due to simple fabrication of very complex architectures, 3D printing offers far greater opportunities to achieve the desired drug release patterns compared to conventional methods of manufacturing dosage forms. Numerous studies describe the successful application of 3D printing in the development of drug delivery systems with different release patterns, from simple immediate and prolonged release to more complex multiphasic release systems and trigger-induced drug release systems. Tailored drug release from 3D-printed drugs can be achieved in two ways: by fabrication of dosage forms of appropriate design or fabrication of device that controls the release of drugs from inserted dosage form prepared by conventional techniques. This article provides a brief overview of different 3D printing approaches used in the development of dosage forms with tailored drug release

    Women in science and equity in Serbia – so near, yet so far

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    The concept of diversity, equity, inclusion and belonging is essential for research and academic programs and institutions worldwide, but although women do not lag behind men at entry and graduation from Serbian universities, equitable leadership does and it further hinders outcomes in every way: from translational science via healthcare up to legislative efforts to protect children, women and elderly. Although all these may seem as l’art-pour-l’art issues when compared to mere survival in war zones on two continents and all issues women face under circumstances of displacement and bans on rights to education, healthcare and sounds of their own voices in public, still it is the ongoing fight for rights lost in silence and where one least expects it that has to push every human being to fight for the oppressed and underprivileged

    Morphological and Magnetic Properties of CuO Nanopowders Doped With Ag

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    CuO je dopiran sa Ag da bi se dodatno poboljšala njegova multiferoična svojstva jer je pokazano da poremećaj u vidu nečistoća može stabilizovati feroelektričnu fazu. Samopropagirajuća sinteza na sobnoj temperaturi primenjena je za sintezu nanočestica čvrstih rastvora oksida bakra i srebra sastava Cu1−xAgxO (x=0,01–0,05). Uspešna reakcija se odvija između metalnog nitrata i natrijum hidroksida. Sintetizovani prahovi su dalje kalcinisani dva puta na 700 °C. Difrakcioni obrazac je snimljen na sobnoj temperaturi i atmosferskom pritisku bez ikakvog ponovnog zagrevanja uzorka. Urađena je Ritveldova metoda za proces rafinacije fitinga, koja je pokazala ugradnju Ag3+ jona u kristalnu rešetku CuO, gde oni zamenjuju Cu2+ jone. SQUID magnetometar je korišćen za ispitivanje magnetnog ponašanja sintetizovanih materijala u temperaturnom opsegu 2-400 К. Uočene su male promene u magnetnim svojstvima Cu1−xAgxO u poređenju sa CuO. Veličina i morfologija čestica su određene transmisijskom elektronskom mikroskopijom (TEM) i skenirajućom elektronskom mikroskopijom (SEM).CuO is doped with Ag to further improve its multiferroic properties since it has been shown that disorder in the form of impurities can stabilize the ferroelectric phase. Self-propagating synthesis at room temperature was applied for the synthesis of nanoparticles of solid solutions of copper and silver oxides with the composition Cu1−xAgxO (x=0.01–0.05). A successful reaction took place be- tween metal nitrate and sodium hydroxide. The synthesized powders were further calcined twice at 700 °C. The diffraction pattern was recorded at room temperature and atmospheric pressure without any reheating of the sample. The Rietveld method for the fitting refining process was performed, which showed the incorporation of Ag3+ ions into the CuO crystal lattice, where they replace Cu2+ ions. The SQUID magnetometer was used to examine the magnetic behavior of the synthesized ma- terials in the temperature range 2-400 K. Small changes in the magnetic properties of Cu1−xAgxO compared to CuO were observed. The size and morphology of the particles were determined by trans- mission electron microscopy (TEM) and scanning electron microscopy (SEM).Procesing '24 : 37. Međunarodni kongres o procesnoj industriji : zbornik radova - Proceedings, 29-31. maj 2024, Beogra

    Pseudomonas aeruginosa mannose-sensitive-hemagglutinin (PA-MSHA) causes anemia in rats after subacute exposure

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    Pseudomonas aeruginosa mannose-sensitive-hemagglutinin (PA-MSHA) is adjuvant cancer therapy with immune-modulating properties. Clinical studies indicate its ability to enhance chemotherapy efficacy and stimulate the immune system against cancer, with mild-to-moderate immune-related side effects such as fever and skin irritation. However, the safety profile of PA-MSHA is not well understood and requires further investigation. Hence, the current study aimed to explore the effects of PA-MSHA on parameters of anaemia in a rat model after 28 days of exposure. Moreover, the study intended to explain gender-specific differences when animals were exposed to three increasing concentrations of PA-MSHA (PA-MSHA 1 (0.09 x 1011 CFU/ml), PA-MSHA 2 (1.8 x 1011 CFU/ml), and PA-MSHA 3 (3.6 x 1011 CFU/ml)), administered intraperitoneally once a week on the 1st, 7th, 14th, and 21st day. At the end of the study period, blood samples were obtained through cardiac puncture and further used for subsequent haematological analysis. The results revealed PA-MSHA’s potential to cause anaemia in a dose- and gender-dependent manner. In females, both PA-MSHA 1 and PA-MSHA 2 significantly decreased the level of erythrocytes and haematocrit, while in males the drop of these parameters was seen only in PA-MSHA 3 group. The PA-MSHA treatment did not impact haemoglobin levels in both genders. However, while male rats experienced a significant dose-dependent decrease in iron blood levels in all investigated groups, the iron levels in female rats did not differ from the control. Mean Corpuscular Volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) parameters were also measured. Male rats showed a dose-dependent increase only in MCHC, while female rats experienced an increase of MCH in the PA-MSHA 2 group and MCHC in all investigated groups. Finally, conducted Benchmark analysis (PROAST Web, version 70.1; https://proastweb.rivm.nl/) revealed that lower concentrations of PA-MSHA can cause a 5% change in effects level related to anaemia in female rats compared to male animals. Calculated BMDL concentration for erythrocytes and haematocrit levels were, respectively: 2.5e05 x 1011 CFU/ml, 7.06e-6 x 1011 CFU/ml for female rats and 0,000858 x 1011 CFU/ml and 9.39e-05 x 1011 CFU/ml for male, while BMDL for MCHC was 0.00947 x 1011 CFU/ml in female animals and 0.0234 x 1011 CFU/ml in males. These findings suggest gender-specific responses to varying doses of PA-MSHA and further underscore the significance of taking gender-specific factors into account when designing and analysing therapeutic approaches that involve PA-MSHA.Abstracts of the 58th Congress of the European Societies of Toxicology (EUROTOX 2024), "Toxicology – A Quest for safe Chemicals and Medicines.", 8-11 September 2024 • Copenhagen, Denmar

    Real-life exposure to toxic metals: impact on thyroid gland function and male reproductive system in rats

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    Toxic metals can disrupt the endocrine system, harming the thyroid and male reproductive function, as indicated by epidemiological and experimental studies. A human biomonitoring study in Serbia determined the levels of toxic metals (Cd, Pb, As, Hg, Cr, and Ni) in the blood to identify real life scenario of exposure. On the basis of the metal measured levels, the doses for the oral 90 days treatment of male Wistar rats were calculated. The experiment included a control group and treatment groups that received doses reflecting the lower confidence limit of the Benchmark dose for effects on hormone levels (M1), median concentrations (M2) and 95th percentiles concentration of each metal (M3). Serum levels of the hormones TSH, fT4, fT3, T4, T3, testosterone, FSH and LH were determined. A histological analysis of the thyroid gland tissue was performed, while the redox status parameters (IMA, MDA, SH groups, GSH and SOD) were determined in the testicular tissue. Additionally, SPINA-GT and SPINA-GD were calculated with the SPINA Thyr software. In group M2 there was a statistically significant decrease in TSH levels and an increase in fT4 levels, while in group M3 a decrease in fT3 levels was observed. The levels of T4 and T3 remained relatively stable in all groups, although a decreasing trend of T3 in M3 and an increasing trend of T4 in M2 were observed. A significant decrease in SPINAGD in all treated groups indicates a decreased activity of peripheral deiodinases, while the secretory activity of the gland was not significantly changed in any of the treated groups. Histological analysis of the thyroid tissue showed changes in all treated groups, despite the fact that in some of the treated groups no changes were observed in the levels of TSH and thyroid hormones, which can be explained by the activation of compensatory mechanisms. The analysis of reproductive hormones in the serum showed that only in the group that was exposed to the highest doses of the tested metals (M3), there was a significant decrease in the level of LH. In the M1 group, group treated with the lowest doses of metals, a decrease in the levels SH groups, GSH, and SOD was observed. This outcome may be a consequence of depletion of antioxidant protection reserves. It can be concluded that environmentally relevant doses of metals mixtures can affect the function and structure of the thyroid gland and the male reproductive system

    Arsenic-contaminated groundwater of the Western Banat (Pannonian basin): Hydrogeochemical appraisal, pollution source apportionment, and Monte Carlo simulation of source-specific health risks

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    Due to rapid urbanization and industrial growth, groundwater globally is continuously deteriorating, posing significant health risks to humans. This study employed a comprehensive methodology to analyze groundwater in the Western Banat Plain (Serbia). Using Piper and Gibbs plots, hydrogeochemistry was assessed, while the entropy-weighted water quality index (EWQI) was used to evaluate groundwater quality. Pollution sources were identified using positive matrix factorization (PMF) accompanied by Pearson correlation and hierarchical cluster analysis, while Monte Carlo simulation assessed health risks associated with groundwater consumption. Results showed that groundwater, mainly Ca–Mg–HCO3 type, is mostly suitable for drinking. Geogenic pollution, agricultural activities, and sewage were major pollution sources. Consumption of contaminated groundwater poses serious non-carcinogenic and carcinogenic health risks. Additionally, arsenic from geogenic source was found to be the main health risks contributor, considering its worryingly elevated concentration, ranging up to 364 μg/L. These findings will be valuable for decision-makers and researchers in managing groundwater vulnerability. Practitioner Points: Groundwater is severely contaminated with As in the northern part of the study area. The predominant hydrochemical type of groundwater in the area is Ca–Mg–HCO3. The PMF method apportioned three groundwater pollution sources. Monte Carlo identified rock dissolution as the primary health risk contributor. Health risks and mortality in the study area are positively correlated

    Sex-Specific Associations between Thyroid Status, Inflammation and Hemostasis Biomarkers in Patients with Subacute Thyroiditis

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    Background: Subacute thyroiditis (SAT) is characterized by profound inflammation and fluctuations in thyroid hormones which may affect the hemostasis balance. This study investigates sex-specific associations between thyroid status, inflammation and hemostasis biomarkers in SAT. Methods: We included 52 patients (40 women and 12 men) treated with non-steroidal anti-inflammatory drugs (NSAID) or methylprednisolone (MPS). Free thyroxine (fT4), thyroid stimulating hormone, C-reactive protein, complete blood count and routine hemostasis parameters were assessed. Results: Both men and women were in hyperthyroid state and had comparable levels of inflammatory biomarkers. A shortened activated partial thromboplastin time (aPTT) was observed in 16.7% of the men and 10% of the women (p = 0.562), and a shortened prothrombin time (PT) was observed in 33% of the men and 12.5% of the women (p = 0.094). In men, aPTT positively correlated with fT4 (r = 0.627; p < 0.05), while PT positively correlated with leukocyte-based inflammatory indices in women (p < 0.05). NSAID-treated patients had lower aPTTs and platelet counts than those treated with MPS (p < 0.05). Principal component analysis extracted “proinflammatory”, “prothrombotic” and “antithrombotic” factors, but the “proinflammatory” factor was the independent predictor of elevated fT4 in women (OR = 2.705; p = 0.036). Conclusions: Our data demonstrated sex-specific associations of thyroid status and inflammatory biomarkers with hemostasis parameters in SAT. Routine hemostasis screening tests may help in monitoring the changes in the hemostasis system over the course of SAT

    Synthesis and Antimicrobial Activity of Newly Synthesized Nicotinamides

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    Antioxidants are promising compounds with antimicrobial activity against drug-resistant pathogens, especially when combined with conventional antimicrobials. Our study aimed to characterize the structure of nicotinamides synthesized from nicotinic acid and thiocarbohydrazones and to evaluate their antibacterial and antifungal activity. Seven nicotinic acid hydrazides (NC 1–7) were synthesized using mono-thiocarbohydrazones with hydroxyl group substituents, along with quinolone, phenolic, and pyridine rings known for their antimicrobial activity. The in vitro antimicrobial activity of NC 1–7, at concentrations ranging from 0.001 to 1 mM, was tested against Staphylococcus aureus (ATCC 6538), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), Klebsiella pneumoniae (NCIMB 9111), and Candida albicans (ATCC 24433) using the broth microdilution method per EUCAST 2024 guidelines. Microorganism survival percentages were calculated based on optical density, and target fishing using the PharmMapper database identified potential molecular targets. The results showed that P. aeruginosa was most susceptible to the compounds, while C. albicans was the least susceptible. NC 3 significantly inhibited P. aeruginosa and K. pneumoniae growth at 0.016 mM, while higher concentrations were required for S. aureus, E. faecalis, and C. albicans. NC 5 was most effective against gram-positive bacteria at 0.03 mM. Only NC 4 completely inhibited C. albicans below 1 mM. NC 3, with the lowest concentration for 50% growth inhibition (0.016–0.064 mM), showed promising antibacterial potential against specific AMR-related proteins (bleomycin resistance protein, HTH-type transcriptional regulator QacR, and streptogramin A acetyltransferase), suggesting that this class of compounds could enhance or restore the activity of established antibiotics

    Grape pomace seed and skin powder as a source of dietary fibre

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    Dietary fibre intake is associated with various health benefits, such as glucose absorption regulation, blood cholesterol level reduction, and the prevention of obesity and cardiovascular diseases. Grape pomace and its constituents (seed and skin) present a good source of dietary fibre. They can be used as gelling or binding water agents. However, they are mostly incorporated into various food products as an integral part of milled pomace flour and powder, contributing to their functional, nutritional, physicochemical, textural, and sensory properties. This study aims to determine the content of dietary fibres in the seven different unfermented pomace seed and skin flours of international (Italien Riesling, Muscat Hamburg, Merlot, Cabernet Sauvignon) and indigenous (Smederevka, Tamjanika, Prokupac) grape varieties. The content of total (TDF), soluble (SDF), and insoluble (ISDF) dietary fibres in seed and skin flours were determined by the enzyme-gravimetric method. The results showed that the content of TDF was almost three times higher in seed flour than in skin flour for all analyzed varieties. Seed flour had more ISDF (66.30–74.18%) and TDF (69.89–75.42%) and less SDF (0.89–4.27%) in comparison to the skin flour. The highest content of ISDF was confirmed in the seed and skin flour of the Cabernet Sauvignon variety. On the other hand, the highest content of SDF was determined in the skin of Italian Riesling and seeds of Smederevka varieties. Although there are differences in content, the seed and skin flour of all analyzed international and indigenous varieties represent a good source of dietary fibre and can be applied to formulate functional and nutritionally valuable food products. To the best of our knowledge, this is the first report on dietary fibre in the seed and skin flour of the autochthonous Prokupac and Tamjanika varieties.14th European Nutrition Conference FENS 2023, Belgrade, Serbia,14th – 17th November 2023

    Procena dijetarnog unosa hemskog i nehemskog gvožđa u populaciji studenata farmacije

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    Iron deficiency is one of the most common nutrient deficiencies worldwide and the leading cause of anemia. Students, particularly females, are especially susceptible to anemia due to irregular diets, inadequate eating habits, and the demands of high physical and mental activity. Low iron levels can negatively impact the intellectual and cognitive abilities of students and jeopardize their overall health. Therefore, it is crucial to meet daily iron requirements primarily through diet. Due to a lack of information about students' lifestyles in Serbia, this study examined variations in iron intake among students focusing on differences by gender and year of study. Seventy students from the Faculty of Pharmacy, University of Belgrade participated in this cross-sectional study by completing an electronic structured questionnaire. The majority of participants were: female (81.4%), students of final year (61.5%), current non-smokers (91.4%), and engaged in physical activity 2 to 3 times per week (52.8%). We found that female students had an average total of 16.2±8.7 mg/day, which is below the recommended intake of 18 mg/day. Only 33.3% of female students met their daily iron requirements through food. In contrast, 69.3% of male students fulfilled their daily requirement of 8 mg/day from food, with an average total iron intake of 13.6±6.3 mg/day. Interestingly, female students consumed significantly more iron from cereals (p = 0.027) and fats (p = 0.035), which contain a non-heme form of iron that has lower bioavailability. This highlights the importance of educating students about the various forms of dietary iron and the factors influencing its absorption. Enhanced knowledge in this area can empower students to adopt healthier eating habits and effectively meet their iron intake needs.Nedostatak gvožđa je jedan od najčešćih nutritivnih deficita širom sveta i vodeći je uzrok anemije. Studenti, pre svega ženskog pola, su posebno podložni razvoju anemije usled loših navika u ishrani, neredovnih obroka praćenih vrlo intenzivnim rasporedom obaveza u toku dana. Nizak nivo gvožđa može negativno da utiče na intelektualne i kognitivne sposobnosti studenata, ali i da ugrozi njihovo sveukupno zdravlje. Stoga, jako je važno zadovoljiti dnevne potrebe za gvožđem, prvenstveno putem ishrane. Zbog nedostatka informacija o životnim stilovima studenata u Srbiji, studija je osmišljena da ispita varijacije u unosu gvožđa među studentima sa fokusom na razlike u polu i godini studija. Sedamdeset studenata Farmaceutskog fakulteta Univerziteta u Beogradu učestvovalo je u ovoj studiji preseka popunjavanjem elektronskog strukturisanog upitnika. Većina učesnika bila je: ženskog pola (81,4%), studenti završne godine (61,5%), nepušači (91,4%) i fizički aktivni 2 do 3 puta nedeljno (52,8%). Rezultati su ukazali da je prosečan ukupan unos gvožđa za studentkinje bio 6,2±8,7 mg/dan, što je ispod preporučenog dnevnog unosa od 18 mg/dan. Samo 33,3% studentkinja je svoje dnevne potrebe za gvožđem zadovoljavalo hranom. Nasuprot tome, 69,3% učenika muškog pola ispunilo je svoje dnevne potrebe od 8 mg/dan iz hrane, sa prosečnim ukupnim unosom gvožđa od 13,6±6,3 mg/dan. Pored toga, studentikinje su konzumirale znatno više gvožđa poreklom iz žitarica (p = 0.027) i masti (p = 0.035), koji sadrže nehemski oblik gvožđa sa manjom bioraspoloživošću. Dobijeni rezultati naglašavaju važnost edukacije studenata o različitim oblicima gvožđa u hrani i faktorima koji utiču na njegovu apsorpciju. Adekvatno znanje u ovoj oblasti može osnažiti studente da usvoje zdravije navike u ishrani i uz pravi izbor hrane efikasno zadovolje svoje potrebe za unosom gvožđa

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