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Inflammatory markers and qualitative and quantitave high density lipoprotein particle characterization in preeclampsia risk assessment
Hipertenzivne komplikacije u trudnoći, uključujući i preeklampsiju, predstavljaju najčešćeuzročnike morbiditeta i mortaliteta, kako majke, tako i fetusa. Prema preporukama Američkog društvaza ginekologiju i akušerstvo (engl. American College of Obstetricians and Gynecologists – ACOG)dijagnoza hipertenzije u trudnoći postavlja se ukoliko je sistolni pritisak ≥140mmHg i/ili dijastolnipritisak ≥90mmHg kod trudnica koje nisu do tada imale dijagnozu hipertenzije. Preeklampsija (PE) sedijagnostikuje sa pojavom de novo hipertenzije (≥140/90 mmHg) nakon 20. nedelje gestacije, sa ili bezproteinurije (≥300 mg/24 h), ali uz kliničke znake edema, hematoloških poremećaja, renalne,pulmonarne ili hepatične disfunkcije. Prosečna globalna incidenca PE iznosi oko 4,6%.Prema Internacionalnom udruženju za ispitivanje hipertenzivnih oboljenja u trudnoći (engl.International Society for the Study of Hypertension in Pregnancy ISSHP), rana PE nastupa pre 34.nedelje gestacije i karakteriše je teža klinička slika češće udružena sa intrauterusnim zastojem u rastuploda (engl. Intrauterine growth restriction, IURG) i prevremenim porođajem, dok se dijagnoza kasnePE postavlja nakon 34. nedelje gestacije, karakteriše je blaža klinička slika i u ređem broju slučajeva jepraćena prevremenim porođajem. PE je multisistemska bolest čija etiologija i patogeneza još uvekintrigira kako stručnu, tako i naučnu javnost.Prema NICE (The National Institute for Health and Care Excellence) preporukama, trudnica je uriziku da razvije PE ukoliko ima više umerenih ili jedan faktor visokog rizika za razvoj PE, pri čemu sufaktori visokog rizika: hipertenzija ili PE u prethodnoj trudnoći, hronična hipertenzija, bolesti bubrega,dijabetes mellitus tip 1 ili 2, autoimune bolesti i višeplodne trudnoće. Faktori umerenog rizika su : prvatrudnoća, starost preko 40 godina, ITM ≥ 35 kg/m2, pozitivna porodična anamneza i period izmeđutrudnoća duži od 10 godina.Skrining koji NICE i ACOG vodiči preporučuju za ranu selekciju i tretman trudnica koje su uriziku ima nisku stopu detekcije, međutim u kombinaciji sa merenjem srednjeg arterijskog pritiska ipulsatilnog indeksa krvnih sudova materice, poboljšava se stepen predikcije. FMF (The Fetal MedicineFoundation) jedini preporučuje pristup procene rizika u prvom trimestru na osnovu faktora rizika majke,ultrazvučnih merenja, merenja protoka kroz arterije materice (UtA-Pi) i merenja biohemijskih markeraangiogenze (placentalnog faktora rasta-PlGF, plazma proteina A udruženog sa trudnoćom-PAPP-A)...Hypertensive complications during pregnancy, including preeclampsia (PE), are among the mostcommon causes of morbidity and mortality for both the mother and fetus. According to the guidelinesfrom the American College of Obstetricians and Gynecologists (ACOG), the diagnosis of pregnancyinducedhypertension is made when the systolic blood pressure reaches ≥140 mmHg and/or diastolicblood pressure ≥90 mmHg in women who had not previously been diagnosed with hypertension.Preeclampsia is diagnosed when de novo hypertension (≥140/90 mmHg) arises after 20 weeks ofgestation, with or without proteinuria (≥300 mg/24 h), accompanied by clinical signs such as edema,hematological disorders, and dysfunction in renal, pulmonary, or hepatic systems. The global averageincidence of PE is around 4.6%.According to the International Society for the Study of Hypertension in Pregnancy (ISSHP),early-onset preeclampsia occurs before 34 weeks of gestation and is characterized by more severeclinical manifestations, often associated with intrauterine growth restriction (IUGR) and preterm birth.Late-onset preeclampsia, diagnosed after 34 weeks of gestation, typically presents with milder symptomsand is less frequently linked to preterm delivery. Preeclampsia is a multisystemic disorder, and itsetiology and pathogenesis remain a subject of ongoing interest within both clinical and scientificcommunities.The National Institute for Health and Care Excellence (NICE) recommends that pregnant womenat risk of developing PE should be identified based on the presence of multiple moderate risk factors ora single high-risk factor. High-risk factors include previous hypertension or preeclampsia, chronichypertension, kidney disease, type 1 or type 2 diabetes, autoimmune diseases, and multiple pregnancies.Moderate risk factors include primigravida status, age over 40 years, body mass index (BMI) ≥35 kg/m²,a positive family history, and a gap of more than 10 years between pregnancies.Although individual screenings are available, both NICE and ACOG guidelines continue torecommend screening for early selection and management of pregnant women at risk. Such screeningshave a low detection rate, but when combined with measurements of mean arterial pressure and theuterine artery pulsatility index (UtA-PI), the detection rate improves. The Fetal Medicine Foundation(FMF) advocates for a first-trimester risk assessment approach based on maternal factors, ultrasoundmeasurements, uterine artery blood flow (UtA-PI), and biochemical markers of angiogenesis (placentalgrowth factor - PlGF and pregnancy-associated plasma protein A - PAPP-A)..
Phenolic Composition in Native and Defatted Nuts and Seeds from the Serbian Market: Analytical Insights and Functional Potential
In this study the phenolic profile of 25 different commercially available edible nuts and seeds from the Serbian market and their defatted by-products were analyzed and compared. Results showed that both native and defatted nuts and seeds are rich sources of various phenolics. Of all the samples analyzed, walnuts, pecan nuts and sunflower seeds (raw and roasted) showed the highest total phenolic content. Sunflower seeds, especially the raw ones, proved to be an exceptionally rich source of chlorogenic acid (116,928.66 μg/g), exceeding the values previously reported in the literature. Similarly, walnut and pecan samples showed the highest levels of protocatechuic and gallic acids, while high flavonoid concentrations in different peanut samples and chia seeds suggest that these commonly consumed foods may have greater bioactive potential than previously thought. The present research confirmed the fact that certain edible nuts and seeds as well as their defatted by-products, already valued for their nutritive values, are affordable, sustainable and rich natural sources of various bioactive phenolics, especially phenolic acids. This work substantiates data on phenolic profiles of edible nuts and seeds, strengthening the foundation for the development of functional foods and contributing to the valorization of agro-industrial residues in line with the principles of circular economy and functional food innovation. Our results also highlight some important and relatively constant characteristics of phenolic composition and content in certain nuts and seeds. These characteristics could potentially serve as quality parameters for the respective samples, enabling the development of products with uniform and standardized composition, one of the prerequisites for high-quality products with pronounced activity
Metode za evaluaciju usluge telefarmacije - sistemski pregled radova
The purpose of this systematic review was to analyze and summarize telepharmacy
evaluation methods. A systematic review of articles was conducted in accordance with the
PRISMA guidelines, using proper inclusion criteria. After the initial keyword search, duplicate
check and screening for titles and abstracts, 22 papers entered the next phase, which was deep
analysis. Most of the studies included in the in-depth analysis were classified as retrospective and
were mainly focused on drug dispensing and pharmacotherapeutics monitoring and management.
According to the Donabedian model, in 16 cases researchers analyzed processes, while 9 times
the focus was set on the outcome. Using the ECHO model, it was found that 13 analyses were
focused on clinical outcomes, 11 on humanistic, while economic outcome issues were explored
in 2 papers. Risk of bias assessment showed that the highest risk of bias came from attrition bias.
There are no unique recommendations on how telepharmacy evaluation should be performed.
Interestingly, ECHO telepharmacy evaluation marginalized economic outcome issues, even
though these outcomes are often a decision factor when it comes to the implementation. Our
results confirm that stronger study designs and more rigorous evaluation methods are recognized
as necessary so that new trends could be identifiedSvrha ovog sistematskog pregleda bila je analiza i sumiranje metoda evaluacije telefarmacije. Sistematski pregled radova sproveden je u skladu sa PRISMA smernicama, uz odgovarajuće kriterijume za uključivanje. Nakon inicijalne pretrage po ključnim rečima, kao i provere duplikata i skrininga naslova i sažetaka, 22 rada su ušla u sledeću fazu dublje analize. Većina studija je klasifikovana kao retrospektivna i uglavnom su bile fokusirane na izdavanje lekova i farmakoterapijsko praćenje i upravljanje lekovima. Prema Donabedijanovom modelu, u 16 slučajeva istraživači su analizirali procese, dok je 9 puta fokus bio postavljen na ishod. Koristeći ECHO model, utvrđeno je da je 13 radova fokusirano na kliničke ishode, 11 na humanističke, dok su pitanja ekonomskog ishoda istražena u 2 rada. Procena rizika od pristrasnosti pokazala je da najveći rizik potiče od pristrasnosti zbog iscrpljivanja. Ne postoje jedinstvene preporuke o tome kako bi trebalo da se uradi evaluacija usluge telefarmacije. Zanimljivo je da je evaluacija telefarmacije ECHO metodom marginalizovala pitanja ekonomskog ishoda, iako su ovi ishodi često faktor odluke kada je u pitanju implementacija ove usluge. Naši rezultati potvrđuju da je prepoznata potreba za jačim dizajnom studija i rigoroznijim metodama evaluacije kako bi se identifikovali novi trendovi
Goat’s Milk Powder Enriched with Red (Lycium barbarum L.) and Black (Lycium ruthenicum Murray) Goji Berry Extracts: Chemical Characterization, Antioxidant Properties, and Prebiotic Activity
The current trend in food innovations includes developing products containing plant ingredients or extracts rich in bioactive compounds. This study aimed to prepare and characterize skimmed thermally treated goat’s milk powders enriched with lyophilized fruit extracts of Lycium ruthenicum Murray (GMLR) and Lycium barbarum L. (GMLB). Proximate analysis, ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), Fourier transform infrared spectroscopy using attenuated total reflection (FTIR-ATR), and electrophoretic analysis were assessed. Total phenolic content (TPC), total protein content, and antioxidant properties of enriched goat milk powders were determined spectrophotometrically, and prebiotic potential was evaluated by the broth microdilution method. A total of 25 phenolic compounds and 18 phenylamides were detected in the enriched goat milk powders. Electrophoretic analysis showed the absence of proteolysis in the prepared powders. The GMLR showed the highest TPC and displayed a ferric ion-reducing power, probably contributed by anthocyanins and some phenylamides. GMLR and GMLB had higher ABTS radical scavenging activity but lower ferrous ion-chelating capacity than control goat′s milk powder. GMLB and GMLR in a dose-dependent manner (0.3–5 mg/mL) showed a growth-promoting effect on probiotic strains. In summary, prepared goji/goat milk powders, primarily GMLR, might be used as prebiotic supplements or functional food additives
Discovery of (3-Phenylcarbamoyl-3,4-dihydro-2H-pyrrol-2-yl)phosphonates as Imidazoline I2 Receptor Ligands with Anti-Alzheimer and Analgesic Properties
Imidazoline I2 receptors (I2-IRs) are altered in Alzheimer’s disease (AD) patients and are associated with analgesia. I2-IRs are not structurally described, and their pharmacological characterization relies on their modulation by highly affine ligands. Herein, we describe the synthesis of (3-phenylcarbamoyl-3,4-dihydro-2H-pyrrol-2-yl)phosphonates endowed with relevant affinities for I2-IRs in human brain tissues. The optimal ADME and pharmacokinetic profile of a selected compound, 12d, secured its in vivo exploration in a senescence accelerated prone 8 mice revealing improvement in the cognitive impairment and unveiling the mechanism of action by analyzing specific AD biomarkers. The treatment of a capsaicin-induced mechanical hypersensitivity murine model with 12d revealed analgesic properties devoid of motor coordination issues. The target engagement of 12d was demonstrated by suppression of the analgesic effect by pretreatment with idazoxan. Overall, 12d is a putative candidate for advancing preclinical phases and supports the modulation of I2-IRs as an innovative approach for therapeutics
A framework for integrated safety in safety-management systems in healthcare
Purpose – Notwithstanding increased patient safety initiatives, adverse events and their impact on those involved continue. The strategic approaches adopted to manage safety by other high-intensity, high-risk and complex industries, such as aviation, have led to an increase in the systems approach for safety management in healthcare organisations. Professional expertise from members of the European Researchers’ Network for Second Victims (ERNST) highlighted that safety and the second victim phenomenon are interconnected across the healthcare ecosystem, extending beyond individual healthcare organisations. Design/methodology/approach – Evidence from different sources, mainly the literature and practitioner professional expertise, was iteratively aggregated and analysed using theoretical systems-based approaches to conceptualise a framework for integrated safety in safety management systems in health. Findings – A cross-sectional view of the healthcare organisation affected by adverse events was presented as a baseline. The whole system (system levels) approach, representing the healthcare system at the micro-, meso- and macro-level, adapting the model for integrated care, was then adopted. A safety-generating culture was considered to integrate and network across the levels of the healthcare system. The “system” (processes) approach, also considering external factors, was incorporated. This iterative conceptualisation led to a proposed framework for integrated safety. This framework was applied to systematically make recommendations for actions to support safety across the healthcare ecosystem. Originality/value – Aggregation of evidence from the literature, together with expertise from professionals and iterative conceptualisation across models adopting the systems approach, led to a comprehensive framework for integrated safety in safety-management systems
Enhancing Transcutaneous Drug Delivery: Advanced Perspectives on Skin Models
Skin acts as a dynamic interface with the environment. Pathological alterations in the skin barrier are associated with skin diseases. These conditions are characterized by specific impairments in epidermal barrier functions.
Despite its protective nature, the skin can be a relevant route of drug administration, both for topical and transdermal therapy, allowing for improved drug delivery and reducing the incidence of adverse reactions.
This manuscript reviews transcutaneous drug delivery as a strategy for treating localized and systemic conditions, highlighting the importance of skin models in the evaluation of drug efficacy and barrier function. It explores advances in in vitro, ex vivo, in vivo, and in silico models for studying cellular uptake, wound healing, oxidative stress, anti-inflammatory and immune modulation activities. Disease-specific skin models are also discussed
Fumaria officinalis Dust as a Source of Bioactives for Potential Dermal Application: Optimization of Extraction Procedures, Phytochemical Profiling, and Effects Related to Skin Health Benefits
Fumaria officinalis (fumitory), in the form of dust, was employed as a source of bioactive extracts whose chemical profile and biological potential were investigated. According to the results of the optimization of the extraction protocol, the extract with the highest polyphenol yield was prepared using fumitory dust under the optimal conditions determined using the statistical tool, 23 full factorial design: 50% ethanol and a 30:1 mL/g ratio during 120 s of microwave extraction (22.56 mg gallic acid equivalent/g of plant material). LC-MS and spectrophotometric/gravimetric analyses quantified the polyphenol, flavonoid, tannin, alkaloid, and protein contents. Caffeoylmalic acid, quercetin dihexoside, quercetin pentoside hexoside, rutin, and methylquercetin dihexoside were the most dominant compounds. The highest total flavonoid, condensed tannin, alkaloid, and protein yields were determined in the extract prepared using microwaves. In addition to the proven antioxidant potential, in the present study, the anti-inflammatory activity of fumitory extracts is also proven in the keratinocyte model, as well as a significant reduction of H2O2-induced reactive oxygen species production in cells and the absence of keratinocyte cytotoxicity. Thus, detailed chemical profiles and investigated biological effects related to skin health benefits encourage the potential application of fumitory dust extracts in dermo-cosmetic and pharmaceutical preparations for dermatological circumstances
Pectin as the carrier for the spray drying of green tea extracts: Tailoring microencapsulation to obtain a prospective nutraceutical
In this study, microencapsulated green tea (GT) extracts, as prospective nutraceuticals, were obtained using spray drying with pectin in different pectin-to-extract (P:E) ratios. Pectin was selected as wall material based on its previously reported superiority to encapsulate phenols, low cost/sustainability of production and intrinsic hypoglycemic and antioxidant potential. A significant degradation (13.74 %) of epigallocatechin was observed in powder without pectin, in contrast to pectin-loaded samples, suggesting its role in chemical stability enhancement of stated compound. FTIR and DSC indicated GT extract bioactives to remain stable during drying. Addition of pectin significantly increased encapsulation efficiency (EE) of epigallocatechin-3-gallate (up to 8.94 %), epicatechin-3-gallate (up to 7.68 %) and caffeine (up to 12.39 %) compared to pectin-free sample. Significant EE enhancement for epigallocatechin-3-gallate was observed until the P:E ratio of 1:1 compared to pectin-free sample, while further increase of pectin share did not lead to a comparative increase in EE. Similar trend was observed for powder flowability, probably due to excess of pectin in the highest P:E ratio (2:1), preventing proper droplets formation, which was also confirmed by SEM. Sample with P:E ratio of 1:1 revealed the slowest release of bioactives, which may be important for facilitating potential GT therapeutic usage. Stated microencapsulate further revealed satisfactory antioxidant (IC50 of 23.70 μg/ml vs. 4.45 μg/ml for ascorbic acid) and hypoglycemic activities (IC50 of 39.48 μg/ml vs. 156.64 μg/ml for acarbose). These findings represent the basis for further experiments regarding usage of the developed GT microencapsulate as nutraceutical applicable in diabetes-related impairments
Associations of excessive gestational weight gain with changes in components of maternal reverse cholesterol transport and neonatal outcomes
Excessive gestational weight gain may be associated with unfavorable pregnancy outcomes. We explored the impact of excessive weight gain on components of HDL metabolism in maternal plasma: sterol composition of HDL particles, distribution of HDL subclasses and SCARB1, ABCA1 and ABCG1 genes expressions and their associations with newborns' characteristics. The study included 124 pregnant women, 58 with recommended and 66 with excessive weight gain. Concentrations of cholesterol synthesis marker, desmosterol, within HDL increased during pregnancy in both groups of participants. In women with excessive weight gain, levels of cholesterol absorption marker, campesterol, within HDL were significantly lower in the 3rd trimester compared to the 1st and 2nd trimesters. Relative proportions of large HDL 2b subclasses increased during pregnancy in women with recommended weight gain. Women with high pre-pregnancy BMI and excessive gestational weight gain had the lowest levels of β-sitosterol within HDL and the highest relative proportions of HDL 3a and HDL 3b subclasses in the 2nd trimester. Large HDL 2b particles were in positive correlation, while smaller HDL 3 subclasses and SCARB1 gene expressions were in negative correlation with APGAR scores. In conclusion, excessive weight gain could contribute to altered metabolism of HDL, and subsequently to poorer neonatal outcomes