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Overcoming the low solubility of novel pyrazoloquinolinone ligand (CW-02-79) by combination of drug-phospholipid complex and nanoemulsion technology: design and physicochemical evaluation
No full textThe low aqueous and oil solubility of the novel
pyrazoloquinolinone ligand (CW-02-79) with significant
binding affinity for sigma-2 receptors in the brain hinders
the development of conventional parenteral formulations
and thus a comprehensive evaluation of its efficacy and
safety. ...Poster presentation: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/5578
Overcoming the low solubility of novel pyrazoloquinolinone ligand (CW-02-79) by combination of drug-phospholipid complex and nanoemulsion technology: design and physicochemical evaluation
No full textThe low aqueous and oil solubility of the novelpyrazoloquinolinone ligand (CW-02-79) with significantbinding affinity for sigma-2 receptors in the brain hindersthe development of conventional parenteral formulationsand thus a comprehensive evaluation of its efficacy andsafety. ...Abstract: [https://farfar.pharmacy.bg.ac.rs/handle/123456789/5577
Fundamentals of 3D printing of pharmaceuticals
No full textWith the progress in medicine during the last several decades, it became clear
that the course of the disease and response to applied therapy differ to a great
extent between patients due to differences in genetic, anatomical, and physiological
characteristics of the patients. This brought into question the current
concept of therapy, so-called one size fits all, where similar drug doses have
been prescribed to a huge number of patients, with neglect of interindividual
differences between patients
Antioxidative and anti-inflammatory effects of taxifolin in H2O2-induced oxidative stress in HTR-8/SVneo trophoblast cell line
No full textOxidative stress has been implicated in numerous pregnancy-related disorders. Biologically active plant sec-
ondary metabolites, which are present in everyday diet, could prove effective therapeutic agents in preventing
these disorders. This study evaluated effects of taxifolin (dihydroquercetin) on ROS production, markers of
oxidative damage to lipids and proteins, activity of antioxidant enzymes and production of pro-inflammatory
cytokines in H2O2-induced oxidative stress in trophoblast HTR-8/SVneo cells. Taxifolin in 10 μM and 100 μM
concentrations attenuated oxidative damage to lipids and proteins, as evidenced by a decrease in MDA content,
extracellular LDH activity, carbonyl groups and nitrite contents. A reduction in the activity of antioxidant en-
zymes SOD, CAT and GPx in cells pre-treated with taxifolin, prior to H2O2 exposure, was also observed, along
with a reduction in intracellular ROS production. Both evaluated concentrations of taxifolin showed anti-
inflammatory activity in trophoblast cells, by reducing production of pro-inflammatory cytokines IL-1β and IL-
6. In this model of H2O2-induced oxidative stress, taxifolin showed marked antioxidative and anti-
inflammatory activities in trophoblast cells, adding further evidence of its protective effects and showing po-
tential as a therapeutic agent in preventing adverse pregnancy outcomes
Expression of miRNAs and proinflammatory cytokines in pregnant women with gestational diabetes mellitus
No full textAltered microRNAs (miRNAs1) and cytokines expression levels are associated with several pregnancy-induced complications. We evaluated the profile of circulating miRNAs (miR-17, miR-29a and miR-181a) and proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-17) in women with gestational diabetes mellitus (GDM2), as well as their potential use as GDM biomarkers. The case-control study included 65 pregnant women divided into 2 groups - GDM and control. Expression levels of miRNAs in plasma samples and cytokines mRNA isolated from peripheral blood buffy coat were analyzed by quantitative real-time PCR (qPCR3). Significant miR-29a downregulation was found in GDM compared to the control group, and was even more significant after adjustments for covariates. miR-17 and miR-181a expression levels did not differ between the examined groups. Expression levels of IL-1β were significantly higher in GDM group compared to controls, while TNF-α, IL-6 and IL-17 did not show significant changes in expression between the two groups. As jugded from the ROC curve analysis, miR-29a and IL-1β had a significant capacity to discriminate between CG and GDM. Additionally, a positive correlation was established between IL-1β and TNF-α in the GDM group. GDM appeared to be associated with altered levels of miR-29a and IL-1β making them markers of this condition
Bio-activity of Chaga mushroom: determining cytotoxicity and antioxidant potential in human cell lines in vitro
No full textThe Chaga mushroom (Inonotus obliquus (Ach. ex Pers.) Pilat), a parasitic mushroom with broad spectrum of metabolites, such as polysaccharides, minerals, carbohydrates and polyphenols, has previously exhibited anti-inflammatory, antioxidant, antigenotoxic and immunomodulatory properties. Although Chaga is a promising natural resource for various applications, there is insufficient data about its biological activity and safety. Thus, it is necessary to investigate how its properties affect the functions of human cells to determine the safety of its use. The cytotoxic effect of Chaga at range of concentrations 25, 50, 75, 100 and 200 μg/mL was investigated in human extravillous trophoblasts HTR-8/SVneo, lung fibroblasts MRC-5 and cervical cancer HeLa cell lines using the MTT and cristal violet (CV) assays. The ability of Chaga to decrease oxidative stress-induced ROS production in MRC-5 cells at 25, 50 and 75 μg/mL was investigated with H2DCFDA assay. The MTT results showed an significant increase in percentage of viable cells at concentrations of 25, 50 and 75 μg/mL in HTR-8/SVneo and of MRC-5 cells, while a significant reduction in cell viability was observed for cancer cells HeLa at concentrations of 100 and 200 μg/mL following the 24h incubation with Chaga. The CV method showed no significant change in the number of adherent cells of HTR-8/SVneo and HeLa cells. The number of adherent MRC-5 cells increased at a Chaga concentration 25 μg/mL, and decreased after 200 μg/mL treatment. Analysis of ROS levels in MRC-5 cells co-incubated with Chaga and 100 μM H2O2 showed that Chaga reduces ROS production at 50 and 75 μg/mL. Overall, the exhibited antioxidant ability of Chaga together with its stimulatory effect on cell viability in normal cells, while having a moderate cytotoxic effect in cancer cells, provides evidence of its biological potential
Secondary findings in 443 exome sequencing data
No full textExome sequencing (ES) may identify and report secondary findings that are unrelated to the primary disease for which the patient underwent genetic testing, but are of potential value in patient care. In this study, we evaluated 81 American College of Medical Genetics (ACMG) medically actionable genes in 443 patients with various neurological disorders. The variants identified were classified and reported following the 2015 ACMG Standards and Guidelines for the interpretation of sequence variants and the ACMG recommendations for reporting secondary findings (v3.2). We detected a total of 17 variants in 17 patients across 9 different genes as secondary findings. Seven heterozygous variants were found in BRCA1, MSH2, and PALB2 which are part of the cancer phenotype category. Nine heterozygous variants were found in MYH7, TTN, LDLR, DSC2, and DSP which are part of the cardiovascular phenotype category. Finally, one heterozygous variant was found in TTR which is part of the miscellaneous phenotype category. Thirteen of above mentioned variants were classified as known pathogenic and four as expected pathogenic. The information collected in our study may lead to the prevention of severe morbidity and mortality and provides additional insight into the genetic background of the Serbian population
The evolution and impact of the PHOENIX Group in European pharmaceutical distribution
No full textIntroduction: Founded by Adolf Merckle in 1994, the PHOENIX group has roots tracing
back over a century. From its inception, PHOENIX Pharmahandel Aktiengesellschaft & Co
quickly established itself as a market leader in Germany. Over the past three decades, the
group has grown significantly, both in size and scope, impacting the pharmaceutical
distribution industry across Europe. This work explores the historical milestones, strategic
expansions, and contributions of the PHOENIX group to the pharmaceutical sector.
Development and Milestones: The initial foundation of the PHOENIX group was marked
by the amalgamation of several regional wholesalers in Germany, positioning the company as
a dominant player from the start. In 1995, the establishment of PHOENIX International
Beteiligungs GmbH set the stage for international expansion. Significant acquisitions in Italy,
Hungary, and the Netherlands marked the beginning of the group's footprint across Europe.
Notable achievements include:
1996-1997: Restructuring in Germany, the introduction of the PHOENIX
International Network (PIN), and the establishment of the Pharmaceutical Science
Award.
1998-2004: Expansion into the UK, France, Austria, and Switzerland. The acquisition
of regional wholesalers and the entry into new markets, such as Croatia and the Czech
Republic, further solidified PHOENIX’s presence.
2005-2010: Strategic acquisitions in Bulgaria, the Netherlands, and Slovakia, and the
launch of the BENU retail brand. Acquisition of the Bulgarian pharmaceutical
wholesaler Libra AG and its subsidiaries in Macedonia, Serbia, and Montenegro.
Beginning of operations under the PHOENIX name in Bosnia and Herzegovina /
Serbia in 2009.
2011-2020: Continued growth with major acquisitions in Italy, the Netherlands, and
the UK. The launch of digital initiatives like the "deine Apotheke" app and the
"gesund.de" health platform demonstrated PHOENIX’s commitment to innovation.
PHOENIX group invests in Serbia in the opening of a new logistics centre near
Belgrade. With the acquisition of the pharmacy chain Goodwill Apoteka, PHOENIX
becomes market leader in Serbian pharmacy retail in 2017.
2022-2024: The largest acquisition in the company's history, incorporating parts of
McKesson Europe, expanded PHOENIX's reach to 29 countries, reinforcing its
position as a European leader in pharmaceutical wholesale and retail.
Conclusion: The PHOENIX group’s journey from a regional wholesaler to a major European
pharmaceutical distributor underscores its adaptability and strategic foresight. By continuously expanding its geographical footprint, investing in digital health solutions, and
maintaining a strong commitment to quality and safety, PHOENIX has played a crucial role
in shaping the pharmaceutical landscape in Europe. As the group celebrates its 30th
anniversary, it stands as a testament to successful innovation and growth in the healthcare
sector, poised to meet future challenges and opportunities
Dihydroquercetin and biochaga reduce H2 O2 -induced DNA damage in peripheral blood mononuclear cells of obese women in vitro—a pilot study
No full textSystemic oxidative stress stemming from increased free radical production and reduced antioxidant capacity are common characteristics of obese individuals. Using hydrogen peroxide (H2O2) to induce DNA damage in vitro, in peripheral blood mononuclear cells (PBMCs) from obese subjects and controls, the DNA protective ability of dihidroqercetin (DHQ) and biochaga (B) alone or in combination, were evaluated. The effects of DHQ and B were estimated under two experimental conditions: pre-treatment, where cells were pre-incubated with the substances prior to H2O2 exposure; and post-treatment when cells were first exposed to H2 H2O2, and further treated with the compounds. DNA damage was evaluated using the comet assay. The results of pre- and post-treatment showed a significant decrease in DNA damage produced by H2O2 in the obese group. This decrease was not significant in control group probably due to a small number of subjects in this pilot study. More prominent attenuation was noted in the pre-treatment with DHQ (250 μg/ml). Analysis of antioxidant properties revealed that DHQ's remarkable reducing power, 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity, and potent∙OH scavenging properties may contribute to strong attenuation of H2O2-induced DNA damage. Also, B showed strong reducing power, DPPH, and ∙OH scavenging ability, while reducing power and DPPH scavenger effects were increased in the presence of DHQ. Conclusively, DHQ and B may reduce H2O2-induced DNA damage in PBMCs from obese subjects when challenged in vitro, and could be valuable tools in future research against oxidative damage-related conditions
Спектрофотометриско определување на кверцетин со користење мицели од цетилтриметиламониум бромид во смеса со мал однос на метанол-вода
No full textA simple and achievable UV-Vis spectrophotometric method for the micro-quantitative determination of quercetin has been developed and validated. This method relies on the formation of supramolecular assemblies of quercetin (QR) and the cationic surfactant cetyltrimethylammonium bromide (CTAB) in a 5 % methanolic aqueous solution. In this solvent medium, CTAB in the presence of QR has a critical micelle concentration of 1.2·10-3 mol l-1 at 24 °C, determined through conductometry. Important analytical parameters such as wavelength, composition of methanol-water mixture, CTAB concentration (cCTAB), and pH were optimized. Under the optimum experimental conditions (λ = 397 nm, 5 % methanol as solvent, cCTAB = 2.0·10-3 mol l-1, and pH = 6.0), Beer’s law was valid for QR concentrations up to 16.9 μg ml-1. The Ringbom optimum QR concentration range was 1.0 - 16.9 μg ml-1. The method sensitivity was 2.03·104 l mol-1 cm-1 (the molar absorptivity) and 0.13 μg ml-1 (limit of detection). The applicability of the proposed method for quantifying QR in pharmaceutical formulations was demonstrated. Furthermore, the proposed UV-Vis spectrophotometric method was successfully applied to the reliably assay of QR, even in the presence of vitamin C.Развиен е и валидиран едноставен и остварлив UV-Vis спектрофотометриски метод за
микроквантитативно определување на кверцетин. Овој метод се потпира на формирање
супрамолекуларни здружувања на кверцетин (QR) и катјонски сурфактант цетилтриметиламониум
бромид (CTAB) во 5 % метанолен воден раствор. Во овој растворувач, CTAB во присуство на QR
има критична мицелна концентрација од 1,2·10–3 mol l–1 на 24 ºC, одредена преку спроводливост.
Извршена е оптимизација на важните аналитички параметри како што се брановата должина,
составот на смесата метанол-вода, концентрацијата на CTAB (cCTAB) и pH. Под оптимални
експериментални услови (
= 397 nm, 5 % метанол како растворувач, cCTAB = 2,0·10–3 mol l–1 и pH =
6,0) важи Беровиот закон за концентрации на QR до 16,9 g ml1. Оптималниот опсег на
концентрација според Ringbom на QR беше 1.0 16.9 g ml1. Чувствителноста на методот беше
2.03·104 l mol1 cm1 (моларна апсорпција) и 0.13 g ml1 (граница на детекција). Докажана е применливоста на предложениот метод за квантифицирање на QR во фармацевтските
формулации. Покрај тоа, предложениот UV-Vis спектрофотометриски метод беше успешно
применет за веродостојна анализа на QR, дури и во присуство на витамин С