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Pneumokokna vakcinacija kod odraslih osoba – korisno, ali nedovoljno upotrebljeno oružje
No full textStreptococcus pneumoniae is a Gram-positive coccus with a characteristic oval shape,
microscopically most often grouped in pairs (diplococci). It is encapsulated microorganism
responsible for a variety of infections in humans, which can be categorized into non-invasive and
invasive forms. Although pneumococcal conjugate vaccines (PCVs) and the 23-valent
pneumococcal polysaccharide vaccine (PPSV23) are widely recommended for routine use in
older adults and adults with underlying conditions across many countries, infections caused by S.
pneumoniae continue to impose a major burden on patients and healthcare systems, and invasive
diseases can leave neurological consequences and have a fatal outcome. Key challenges include
infections caused by serotypes not present within vaccines and suboptimal vaccination coverage
among older adults, even in developed countries. PCVs differ from PPSV23 as capsular
polysaccharides are conjugated with a carrier protein, while PPSV23 contains 23 purified capsular
polysaccharides. In addition, an important difference between PPSV23 and PCVs is that PPSV23
induces T-cell independent humoral immune response, while, in contrast, conjugate vaccines
induce T-cell dependent immune response leading to the formation of specific antibodies and
memory B-cells. The pneumococcal vaccination schedule recommended for adults aged between
19 and 64 and those over the age of 65 depends on chronic medical conditions. In 2021, the United
States approved two new vaccines, PCV15 and PCV20, while in 2024, the Food and Drug
Administration approved PCV21 for adult use. Despite available vaccines, vaccination coverage
in adults remains low, indicating that vaccination, as the most crucial preventive measure, is not
being applied sufficiently. To raise awareness of adult vaccination, educational campaigns
providing evidence-based information addressing misinformation about vaccines and actively
involving healthcare workers in primary care settings to promote vaccination are also essential.Streptococcus pneumoniae je Gram-pozitivna koka karakterističnog ovalnog oblika,
mikroskopski najčešće grupisana u parove (diplokoke). Virulentni sojevi produkuju kapsulu i
mogu uzrokovati širok spektar bolesti kod ljudi, koje se klasifikuju u neinvazivne i invazivne
forme. Iako su dva tipa vakcina protiv pneumokoka – konjugovane pneumokokne vakcine (PCV)
i 23-valentna pneumokokna polisaharidna vakcina (PPSV23) – preporučene za rutinsku primenu
kod odraslih u mnogim zemljama, pneumokokne infekcije i dalje značajno opterećuju zdravstveni
sistem, a invazivna oboljenja mogu ostaviti neurološke posledice i imati fatalan ishod. Glavni
izazovi uključuju infekcije uzrokovane serotipovima koji nisu obuhvaćeni vakcinama i nizak
obuhvat vakcinacijom među starijim odraslim osobama, čak i u razvijenim zemljama. PCV
vakcine se razlikuju od PPSV23 jer su kapsularni polisaharidi konjugovani sa proteinskim
nosačem, dok PPSV23 sadrži 23 prečišćena kapsularna polisaharida. Takođe, važna razlika
između PPSV23 i PCV vakcina je ta što PPSV23 izaziva T-ćelijski nezavisnu aktivaciju B
limfocita, dok, s druge strane, konjugovane vakcine izazivaju T-celijski zavisnu aktivaciju B
limfocita, što može dovesti do imunološke memorije B-ćelija. Preporučeni raspored vakcinacije
protiv pneumokoka za odrasle osobe starosti 19 – 64 godine ili starije od 65 godina zavisi od
pratećih hroničnih bolesti. Sjedinjene Američke Države su 2021. godine odobrile dve nove
vakcine, PCV15 i PCV20, a 2024. godine, Američka agencija za hranu i lekove odobrila je PCV21
za primenu kod odraslih. Uprkos dostupnim vakcinama, obuhvat vakcinacijom kod odraslih je i
dalje nizak, što ukazuje na to da vakcinacija, kao najvažnija preventivna mera, nije dovoljno
primenjena. Da bi se povećala svest o vakcinaciji odraslih, neophodne su edukativne kampanje
koje pružaju informacije zasnovane na naučnim dokazima, razrešavanje dezinformacija u vezi sa
vakcinama, kao i aktivno angažovanje zdravstvenih radnika u primarnoj zdravstvenoj zaštiti u
promociji vakcinacije
Interfacial Molecular Interactions as Determinants of Nanostructural Preservation in Ibuprofen-Loaded Nanoemulsions and Nanoemulsion Gels
No full textBackground/Objectives: Nanoemulsions (NEs) are highly promising drug delivery systems that can be made user-friendlier by thickening to nanoemulsion gels (NEGs). However, in order to be regulatory accepted, such a transformation requires systematic understanding of the underlying interactions and stabilization mechanisms, especially when the incorporated active pharmaceutical ingredient may infiltrate the stabilizer layer. Methods: NEs with/without ibuprofen were submitted through direct vs. indirect gelation using three different gelling agents (carbomer 980, xanthan gum, or polyacrylate crosspolymer-6). Multi-technique characterization was employed to demonstrate nanoparticle preservation within the gel networks, a point often neglected when studying nanogels. Results: The nanoemulsion with the most favorable properties (55.07 ± 0.82 nm, PDI 0.075 ± 0.022) was successfully transformed into nanoemulgels with all three gelling agents, both by an indirect and direct approach. The combination of Fourier-transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) revealed complex interactions and electron paramagnetic resonance spectroscopy (EPR)-discerned localization of the small-molecule model drug within the surfactants/co-solvents’ microenvironment, while atomic force microscopy (AFM) successfully visualized nanodroplets, with or without the presence of aggregates originating from the applied gelling agent. Conclusions: A series of complementary techniques confirmed the preservation of nanodroplets after transformation while highlighting the potential of novel polyacrylate crosspolymer-6 to produce robust gel network while effectively increasing zeta potential from −11.07 to −30.5 mV and allowing for satisfactory ibuprofen release from nanoparticles
In memoriam - prof. emeritus dr Danica Agbaba (1953-2024)
No full textUpravo smo ove subote (29. novembra 2025. godine) prigodnim pomenom na
Zemunskom groblju obeležili godišnjicu smrti (4. decembra 2024. godine) naše prerano
preminule prof. emeritus dr Danice Agbabe (1953–2024). ...In memoriam (Springer): [https://farfar.pharmacy.bg.ac.rs/handle/123456789/6409
Semisolid 3D printing of thin films: influence of layer configuration and polymer composition on film performances
No full textSemisolid 3D printing offers a versatile
approach for preparing thin films with tailored
drug loading and microstructural design. While
such films are typically developed for
immediate release to ensure rapid onset of
action, especially in pediatric and geriatric
populations, prolonged drug release is often
preferred to maintain therapeutic levels and
reduce dosing frequency [1]. This study
investigates the influence of polymer
composition and layer configuration on the
mechanical and drug release performance of 3D
printed thin films containing paracetamol as a
model drug
In Memoriam of Professor Emeritus Dr. Danica Agbaba (1953 − 2024)
No full textProfessor Emeritus Danica Agbaba, PhD, full professor at the Faculty of Pharmacy, University of Belgrade, passed away on December 4, 2024. ...In memoriam (Arhiv za farmaciju): [https://farfar.pharmacy.bg.ac.rs/handle/123456789/6410
Povezanost između sistemske inflamacije i metabolizma lipida u razvoju preeklampsije
No full textPreeclampsia (PE) is a pregnancy complication marked by hypertension (≥ 140/90 mmHg)
and proteinuria (≥ 300 mg/24 h), with an unclear pathogenesis involving inflammation and
dyslipidemia. This study aimed to longitudinally examine changes in lipid status parameters and
inflammatory markers in pregnant women at high risk for PE and those who developed PE.
Among 91 women, 20 developed PE (PE group), and 71 were high-risk (HR group). Both groups
were monitored at four points: T1-first, T2-, T3-third trimester, and T4-pre-delivery. Lipid
markers (triglycerides (TG), total cholesterol (TC), HDL-C, LDL-C, apolipoproteins A-I and B-
100) and inflammatory markers (high-sensitivity C-reactive protein (hsCRP), resistin, serum
amyloid A (SAA), and macrophage chemotactic protein-1 (MCP-1)) were assessed. Results
showed significantly higher TG, resistin, and MCP-1 concentrations in the PE group compared
to the HR group at T1 (p < 0.05, p < 0.01, p < 0.01, respectively). During pregnancy, both groups
exhibited increases in TG, TC, LDL-C, SAA, and MCP-1 (p < 0.001), while HDL-C and resistin
increased only in the HR group (p < 0.001). PE development is associated with atherogenic lipid
changes, characterized by hypertriglyceridemia and no increase in HDL-C, with elevated SAA
potentially diminishing HDL’s protective role.Preeklampsija (PE) je komplikacija trudnoće koju karakterišu hipertenzija (≥ 140/90
mmHg) i proteinurija (≥ 300 mg/24 h), sa nejasnom patogenezom koja uključuje inflamaciju i
dislipidemiju. Cilj ove studije bio je longitudinalno ispitivanje promena u koncentracijama
parametara lipidnog statusa i inflamatornim markerima kod trudnica sa visokim rizikom za razvoj
PE i onih koje su razvile PE. Od 91 žene, 20 je razvilo PE (PE grupa), a 71 je bila visokorizična
(HR grupa). Obe grupe su praćene u četiri vremenske tačke: T1-prvi, T2-drugi, T3-treći trimestar,
i T4-predporođaj. Kvantifikovani su lipidni parametri (trigliceridi (TG), ukupni holesterol (TC),
HDL-C, LDL-C, apolipoproteini A-I i B-100) i inflamatorni markeri (visokoosetljivi C-reaktivni
protein (hsCRP), rezistin, serumski amiloid A (SAA) i monocitni hemoatraktantni protein-1
(MCP-1)). Rezultati su pokazali značajno veće koncentracije TG, resistina i MCP-1 u PE grupi u
odnosu na HR grupu u T1 (p < 0.05, p < 0.01, p < 0.01, respektivno). Tokom trudnoće, obe grupe
su pokazale porast koncentracija TC, LDL-C, TG, SAA i MCP-1 (p < 0.001), dok su koncentracije
HDL-C i resistina značajno porasle samo u HR grupi (p < 0.001). Razvoj PE je povezan sa
aterogenim promenama lipidnog statusa, okarakterisanim hipertrigliceridemijom, bez promena u
HDL-C koncentracijama, pri čemu povećanje SAA potencijalno smanjuje zaštitnu ulogu HDL-a
Dual activity of newly synthesized Zn(II) and Cu(II) schiff base complexes as a potential solution for global challenges in the fight against priority microorganisms
No full textThe increasing prevalence of antimicrobial resistance (AMR) poses a significant global challenge, necessitating the development of novel and improved therapeutic strategies. Oxidative stress is a major factor in various diseases, emphasizing the need for compounds with dual antimicrobial and antioxidant properties. This study aims to investigate the synthesis, structural characterization, and bioactivity of novel Zn(II) (2a-b) and Cu(II) (3a-b) complexes, derived from structurally related imines incorporating salicylic aldehyde and p-OH benzyl amine (1a) or tyramine (1b). The objective is to explore the relationship between metal coordination and biological activity, focusing on both antimicrobial and antioxidant effects. A comprehensive methodology was employed, including different spectroscopic techniques and molecular docking studies. Antimicrobial activity was assessed through minimum inhibitory concentration (MIC) assays, while antioxidant potential was evaluated via free radical scavenging assays. Molecular docking simulations provided insight into the binding affinities of the complexes with DNA gyrase (DNAg) and cytochrome P450 14-α sterol demethylase (CYP51B). While Zn(II) complexes (2a-b) demonstrated antimicrobial efficacy against priority microorganisms, Cu(II) complex (3a) exhibited notable antioxidant activity. Docking studies revealed that complexes 3a and 3b displayed strong affinity for DNAg (ΔGbind -8.81 and -8.54 kcal mol-1, Ki 0.35 μM for 3a), while complex 2a showed exceptional affinity for CYP51B (-10.22 kcal mol-1, Ki 0.03 μM). Fluorescence spectroscopy confirmed strong interactions between 2a and 3a with Bovine Serum Albumin. These findings demonstrate the promising dual properties of Zn(II) and Cu(II) Schiff base complexes, combining antimicrobial and antioxidant activities, and suggest their potential therapeutic applications in addressing AMR and oxidative stress-related diseases
Physiologically Based Pharmacokinetic Modeling for Predicting Drug Levels After Bariatric Surgery: Vardenafil Exposure Before vs. After Gastric Sleeve/Bypass
No full textBariatric surgery involves major changes in the anatomy and physiology of the gastrointestinal tract, which may alter oral drug bioavailability and efficacy. Phosphodiesterase-5 inhibitor (PDE5i) drugs are the first-line treatment of erectile dysfunction, a condition associated with a higher BMI. In this paper, we examine the PDE5i vardenafil for possible post-bariatric changes in solubility/dissolution and absorption. Vardenafil solubility was determined in vitro, as well as ex vivo using aspirated gastric contents from patients prior to vs. following bariatric procedures. Dissolution was tested in vitro under unoperated stomach vs. post-gastric sleeve/bypass conditions. Lastly, the gathered solubility/dissolution data were used to produce an in silico physiologically based pharmacokinetic (PBPK) model (GastroPlus®), where gastric volume, pH, and transit time, as well as proximal GI bypass (when relevant) were all adjusted for, evaluating vardenafil dissolution, gastrointestinal compartmental absorption, and pharmacokinetics before vs. after different bariatric procedures. pH-dependent solubility was demonstrated for vardenafil with low (pH 7) vs. high solubility (pH 1–5), which was confirmed ex vivo. The impaired dissolution of all vardenafil doses under post-gastric bypass conditions was demonstrated, contrary to complete (100%) dissolution under pre-surgery and post-sleeve gastrectomy conditions. Compared to unoperated individuals, PBPK simulations revealed altered pharmacokinetics post-gastric bypass (but not after sleeve gastrectomy), with 30% lower peak plasma concentration (Cmax) and 40% longer time to Cmax (Tmax). Complete absorption after gastric bypass is predicted for vardenafil, which is attributable to significant absorption from the large intestine. The biopharmaceutics and PBPK analysis indicate that vardenafil may be similarly effective after sleeve gastrectomy as before the procedure. However, results after gastric bypass question the effectiveness of this PDE5i. Specifically, vardenafil’s onset of action might be delayed and unpredictable, negatively affecting the practicality of the intended use
Evaluation of the effects of a diabetes type 2 rat model and semaglutide treatment on the sucrose preference test
No full textDiabetes type 2 (T2D) is the most common metabolic disorder worldwide and can be associated with eating disorders and/or depression. Recent evidence suggests that semaglutide, glucagon-like peptide 1 agonist and antidiabetic drug, may affect appetite, food preference, but also mood, although preclinical data are lacking or conflicting. We therefore investigated the effects of T2D model based on high-fat diet and streptozotocin administration in middle-aged rats and semaglutide treatment on anhedonia or binge eating. Sprague-Dawley rats of both sexes were fed high-fat or control diet and treated with streptozotocin or vehicle. When T2D model or control was developed, rats were treated or not with semaglutide/solvent. These animals were studied in separate cohorts subjected to behavioral battery including sucrose preference test. The main effects of model, sex and treatment were found to be significant for sucrose preference, with T2D rats, female rats and semaglutide-treated rats, respectively, with the former showing decreased and two latter increased levels compared to respective controls. In addition, the main effects of model and sex showed differences in sucrose intake per 100 g animal body mass (SI), with T2D and female animals, showing decreased and increased levels, respectively, compared to their respective controls. Our results showed that T2D rats had reduced sucrose intake compared to controls, which could be related to anhedonia, and SI seems to be a more appropriate parameter than sucrose preference for this model. Semaglutide treatment had no effect on this parameter, which emphasizes the importance of dietary changes in T2D and warrants further investigation
Unraveling the binding mechanism of olanzapine with human serum transferrin: a multispectroscopic and computational investigation
No full textThe interaction between olanzapine (OLZ) and human serum transferrin (Tf), both in the absence and presence of Fe3⁺, was analyzed using multispectroscopic methods, molecular docking, and molecular dynamics simulations under physiological conditions. Spectroscopic results confirmed OLZ’s strong affinity for Tf, driven by static interactions complemented by minor dynamic effects. The values of the binding constants, Ka (2.48 × 108, 4.73 × 107, 1.13 × 107 at 296, 303 and 310 K, respectively) indicate that OLZ-Tf complex is more stable at lower temperatures. Negative thermodynamic parameter values (enthalpy, ΔH0 = -168.46 kJmol−1; entropy, ΔS0 = −408.63 JK−1 mol−1; and free energy, ΔG0 = −47.50 kJmol−1) suggest an exothermic and spontaneous binding process dominated by hydrogen bonding and van der Waals forces. Structural changes in Tf upon OLZ binding confirmed by spectroscopic measurements. Results of molecular docking revealed that OLZ exhibits a stronger binding affinity for apotransferrin (Fe3+-free Tf) than for holo-transferrin (iron-bound Tf), with preferential interaction in the N-lobe. The effect of Fe3+ on OLZ-Tf interactions was examined, confirming that iron modulates the binding mechanism. Molecular dynamics (MD) simulations supported these findings, showing OLZ stabilizes Tf’s structure while maintaining its flexibility for transport. These results suggest that OLZ can bind to Tf and influence OLZ’s bioavailability and pharmacokinetics, offering potential implications for drug design and clinical applications in altered iron homeostasis