Procter & Gamble (United Kingdom)
FarFar - Repository of the Faculty of Pharmacy, University of BelgradeNot a member yet
6247 research outputs found
Sort by
The Effects of Pregestational Overweight and Obesity on Maternal Lipidome in Pregnancy: Implications for Newborns’ Characteristics
Get PDFObesity is an important risk factor for the development of pregnancy complications. We investigated the effects of pregestational overweight and obesity on maternal lipidome during pregnancy and on newborns’ characteristics. The study encompassed 131 pregnant women, 99 with pre-pregnancy body mass index (BMI) < 25 kg/m2 and 32 with BMI ≥ 25 kg/m2. Maternal lipid status parameters, plasma markers of cholesterol synthesis and absorption and sphingolipids were determined in each trimester. Data on neonatal height, weight and APGAR scores were assessed. The results showed a higher prevalence (p < 0.05) of pregnancy and childbirth complications among the participants with elevated pregestational BMI. Levels of total cholesterol, HDL-cholesterol (p < 0.05) and LDL-cholesterol (p < 0.01) were significantly lower, and concentrations of triglycerides were higher (p < 0.05) in women with increased pre-gestational BMI. Lower concentrations of the cholesterol synthesis marker, desmosterol, in the 2nd trimester (p < 0.01) and the cholesterol absorption marker, campesterol, in each trimester (p < 0.01, p < 0.05, p < 0.01, respectively) were also found in this group. Markers of maternal cholesterol synthesis were in positive correlation with neonatal APGAR scores in the group of mothers with healthy pre-pregnancy weight but in negative correlation in the overweight/obese group. Our results indicate that gestational adaptations of maternal lipidome depend on her pregestational nutritional status and that such changes may affect neonatal outcomes
Услови синхронизациjе у ланчаном моделу клизишта са шумом и кашњењем у вези
No full textWe examine the conditions for synchronization of landslide stochastic chain model with delayed coupling. Firstly, a new chain model for landslide dynamics is proposed, with the included effect of delayed coupling and background noise. The model is of the microscopic type, where the state of each block in the chain is influenced by the previous state of the same block and its neighbors as well as by noise. Secondly, we examine the stochastic synchronization of such a system of stochastic delay-differential equations. A sufficient condition for the exponential mean square stability of the synchronization is obtained. The sufficient condition indicates that the uni-directional asymmetric coupling induces the synchronization much more efficiently than the bi-directionally symmetric one. From the practical viewpoint, the results obtained confirm that different parts of the large unstable slope could exhibit synchronized activity under certain conditions, which indicates their possible larger influence on the structures (and generation of corresponding deformation) compared to the individual effect of unsynchronized activities.Резиме. У раду испитуjемо услове за синхронизациjу ланачног модела клизи- шта са шумом и кашњењем у вези. Као прво, предлаже се нови ланчани модел динамике клизишта, са укљученим ефектом кашњења у вези и позадинског шума. Модел jе микроскопског типа, где на стање сваког блока у ланцу утиче претходно стање истог блока, као и и суседних блокова, укључуjући и утицаj шума. Као друго, испитуjемо стохастичку синхронизациjу таквог система сто- хастичких диференциjалних jедначина са кашњењем. Као резултат, добиjа се довољан услов за експоненциjалну средње квадратну стабилност синхрониза- циjе, коjи указуjе на то да jедносмерно асиметрично повезивање блокова доводи до синхронизациjе много ефикасниjе од двосмерно симетричног. Са практичне тачке гледишта, добиjени резултати потврђуjу да би различити делови велике нестабилне падине могли да испољаваjу синхронизовану активност под одре- ђеним условима, што указуjе на њихов могући већи утицаj на конструкциjе (и генерисање одговараjућих деформациjа) у односу на индивидуални ефекат несинхронизованих активности различитих делова падине
Beneficial effects of a new probiotic formulation on adipocytokines, appetite-regulating hormones, and metabolic parameters in obese women
No full textObesity is often accompanied by low-grade chronic inflammation and metabolic syndrome. It has been established that microbiota influences many physiological processes, including the development of obesity, and dysbiosis has been observed in obese individuals. In this study, we aimed to evaluate the impact of a new probiotic formulation, containing two probiotic strains and the bioactive compound octacosanol, on body weight, metabolic parameters, and concentrations of certain adipocytokines and appetite-regulating hormones in obese women. This double blind placebo-controlled supplementary intervention study included twenty-five women in the intervention group and twenty-three in the placebo group, and it lasted 12 weeks. Daily oral supplementation included 7 × 1010 CFU of Lactiplantibacillus plantarum 299v (DSM9843), 5 × 109 CFU of Saccharomyces cerevisiae var. boulardii (DBVPG6763), and 40 mg of octacosanol or placebo. Body weight, metabolic parameters, adipocytokines, and appetite-regulating hormones were assessed before (T0) and after the intervention (T1). After the intervention, significantly lower median concentrations of CRP (p = 0.005) and IL-6 (p = 0.012) were measured in the intervention group than the baseline, while the median concentrations of ghrelin (p = 0.026) and HDL-cholesterol (p = 0.03) were significantly increased. The intervention group had lower CRP levels (p = 0.023) and higher ghrelin levels (p = 0.006) than the placebo group. Significant changes in BMI between groups were not observed. In summary, although the new probiotic formulation showed beneficial effects on IL-6, CRP, HDL, and ghrelin levels, its potential effects on regulating triglyceride, insulin, and glucose levels require further studies before the novel dietary intervention could be considered a useful adjuvant therapy and an effective strategy for the management of obesity and obesity-associated comorbidities. © 2024 The Royal Society of Chemistry
Drugs with a negative impact on cognitive functions (part 3): antibacterial agents in patients with chronic kidney disease
Get PDFThe relationship between chronic kidney disease (CKD) and cognitive function has received increased attention in recent years. Antibacterial agents (ABs) represent a critical component of therapy regimens in patients with CKD due to increased susceptibility to infections. Following our reviewing work on the neurocognitive impact of long-term medications in patients with CKD, we propose to focus on AB-induced direct and indirect consequences on cognitive function. Patients with CKD are predisposed to adverse drug reactions (ADRs) due to altered drug pharmacokinetics, glomerular filtration decline, and the potential disruption of the blood–brain barrier. ABs have been identified as a major cause of ADRs in vulnerable patient populations. This review examines the direct neurotoxic effects of AB classes (e.g. beta-lactams, fluoroquinolones, aminoglycosides, and metronidazole) on the central nervous system (CNS) in patients with CKD. We will mainly focus on the acute effects on the CNS associated with AB since they are the most extensively studied effects in CKD patients. Moreover, the review describes the modulation of the gut microbiota by ABs, potentially influencing CNS symptoms. The intricate brain–gut–kidney axis emerges as a pivotal focus, revealing the interplay between microbiota alterations induced by ABs and CNS manifestations in patients with CKD. The prevalence of antibiotic-associated encephalopathy in patients with CKD undergoing intravenous AB therapy supports the use of therapeutic drug monitoring for ABs to reduce the number and seriousness of ADRs in this patient population. In conclusion, elucidating AB-induced cognitive effects in patients with CKD demands a comprehensive understanding and tailored therapeutic strategies that account for altered pharmacokinetics and the brain–gut–kidney axis
Zn0-Induced Cytotoxicity and Mitochondrial Stress in Microglia: Implications of the Protective Role of Immunoglobulin G In Vitro
Get PDFBackground: Zinc (Zn), an essential micronutrient, regulates and maintains neurological functions. However, both Zn deficiency and excess can cause oxidative stress and neurodegenerative diseases. As previously reported, immunoglobulin G (IgG) can modulate oxidative stress in various disorders. Aims: To investigate whether IgG treatment can alleviate oxidative stress caused by Zn0 on microglia in vitro. Study Design: In vitro study. Methods: The feasibility of Zn0 treatment was evaluated using the MTS assay. Oxidative stress following treatment with Zn0, either alone or with IgG supplementation, was determined with dihydrorhodamine 123 staining. Flow cytometry was employed to ascertain the intracellular protein levels of TRIM21, PINK, PARKIN, MFN2, Beclin-1, and active LC3B. Methods: The feasibility of Zn0 treatment was evaluated using the MTS assay. Oxidative stress following treatment with Zn0, either alone or with IgG supplementation, was determined with dihydrorhodamine 123 staining. Flow cytometry was employed to ascertain the intracellular protein levels of TRIM21, PINK, PARKIN, MFN2, Beclin-1, and active LC3B. Results: In silico screening confirmed the association between Zn0 cytotoxicity and apoptosis. Furthermore, oxidative stress was identified as a critical mechanism that underlies Zn0 neurotoxicity. The in silico analysis revealed that Zn can interact with the constant region of the Ig heavy chain, suggesting a potential role for IgG in alleviating Zn0-induced cytotoxicity. Experimental findings supported this hypothesis, as IgG administration significantly reduced Zn0-induced mitochondrial stress in a dose-dependent manner. The upregulation of PINK1 levels by Zn0 exposure suggests that mitochondrial injury promotes mitophagy. Interestingly, Zn0 decreased TRIM21 levels, which is reversed by IgG administration. Conclusion: These findings elucidate the cellular responses to Zn0 and highlight the potential use of intravenous immunoglobulin in mitigating the adverse effects of acute Zn0 exposure
Targeting noncoding RNAs to treat atherosclerosis
Get PDFNoncoding RNAs (ncRNAs) are pivotal for various pathological processes, impacting disease progression. The potential for leveraging ncRNAs to prevent or treat atherosclerosis and associated cardiovascular diseases is of great significance, especially given the increasing prevalence of atherosclerosis in an ageing and sedentary population. Together, these diseases impose a substantial socio-economic burden, demanding innovative therapeutic solutions. This review explores the potential of ncRNAs in atherosclerosis treatment. We commence by examining approaches for identifying and characterizing atherosclerosis-associated ncRNAs. We then delve into the functional aspects of ncRNAs in atherosclerosis development and progression. Additionally, we review current RNA and RNA-targeting molecules in development or under approval for clinical use, offering insights into their pharmacological potential. The importance of improved ncRNA delivery strategies is highlighted. Finally, we suggest avenues for advanced research to accelerate the use of ncRNAs in treating atherosclerosis and mitigating its societal impact
Chitosan-clay composite films: investigation of functional and antibacterial properties for potential biomedical application
No full textThe preparation of polymer-clay composites is gaining increasing attention as these functionalizedmaterials can be used in biomedical fields (Dong et al., 2021). Chitosan is the most abundant natural cationicpolysaccharide polymer, frequently used because of its special properties such as non-toxicity, biocompatibility,biodegradability, antibacterial activity, and film-forming ability (Jagdale et al., 2024). In this study, chitosanbasedcomposite films with or without natural clay were prepared, and their functional properties (mass,thickness, and swelling), as well as their antibacterial activity, were investigated. The natural bentonite fromthe Beretnica deposit in the Republic of Serbia (BB) (CEC = 120 meq/100 g), commercial low molecularweight chitosan (Sigma-Aldrich, USA), glycerol (as plasticizer) and a 1% acetic acid solution were used forthe preparation of composite films by casting and solvent evaporation, at polymer/clay ratios: 1.5:0.0 and1.5:1.0. The samples were designated as F0 and FBB, respectively. The average mass and thickness of the FBBcomposite film (24±2 mg, i.e., 140±6 μm) were increased compared to the parameters of the film preparedwithout clay (F0) (12±1 mg, i.e., 75±8 μm). The swelling capacity of the films after 4 h (pH phosphate buffer5.8 at 37°C) was 536±54% for F0 and 302±43% for FBB. Although the FBB sample showed slightly lowerswelling, the obtained results indicated that the composite film could absorb a considerable amount of water,which is very important in the case of its application as a wound dressing (Morgado et al., 2015).The antibacterial activity of the prepared films was tested against Enterococcus faecalis and Escherichiacoli using the log-reduction method. Both F0 and FBB inhibited the growth of E. coli, by 0.64 log10 CFU/mL for F0 and 1.60 log10 CFU/mL for FBB, compared to the 100% cellulose film used as control, althoughthe inhibition of F0 was not significant. On the other hand, sample F0 showed pronounced inhibitory activity(by 1.56 log10 CFU/mL) against E. faecalis, while the sample FBB showed bactericidal activity inhibiting thechosen Gram+ bacteria growth by 4.0 log10 CFU/mL, compared to the control sample. The results indicatethat the addition of BB significantly increases the antibacterial activity of chitosan films.Considering the wide distribution of natural bentonite (such as BB in this study), which significantly improvesthe properties of chitosan film in terms of antimicrobial potential, these results have a future perspective in theproduction of affordable and effective dressings, with still high swelling capacity, for the topical treatment ofdamaged and/or infected skin
Chemical composition and antimicrobial activity of essential oil of helichrysum italicum from mediterranean coast
No full textGas chromatography-mass spectrometry has been used in the analysis of the chemical characteristics of the essential oil of
Helichrysum italicum, cultivated in Montenegro, complete with its antimicrobial activity, the evaluation of which has been
done against 7 microorganisms, involving Gram-positive and Gram-negative bacteria as well. The evaluation led to thirtyseven compounds being identified in the essential oil, with the following components: α-pinene (16.62%), -curcumene
(14.06%), -selinene (7.39%) and neryl acetate (6.04%). In addition, the importance of the following minor compounds found
in the essential oil has been confirmed: -caryophyllene (5.02%), bisabolane (4.28%), italicene (4.16%). The results of the
antimicrobial activity tests have revealed that the essential oil of Helichrysum italicum, has rather strong antimicrobial activity,
especially against Enterococcus faecalis (MIC is 0,008 mg/mL) and activity against Staphylococcus epidermidis (MIC is
0,016mg/mL) and Staphylococcus aureus (MIC is 0,062 mg/mL). The MIC value according to Escherichia coli, Klebsiella
pneumoniae, Salmonella abony and Pseudomonas aeruginosa is greater than 4 mg/mL. Results have shown that the immortelle
essential oil exhibited significant antibacterial activity against Gram-positive bacteria, and less against Gram-negative bacteria.In cadrul studiului a fost determinată compoziția chimică a uleiului esențial de Helichrysum italicum, cultivat în Muntenegru,
și evaluată activitatea sa antimicrobiană. În uleiul esențial au fost identificați 37 de compuși, dintre care: α-pinen (16,62%), ℽ-
curcumen (14,06%), β-selinen (7,39%) și acetat de neril (6,04%). S-a demonstrat activitatea antimicrobiană a uleiului volatil
de Helichrysum italicum, în special împotriva Enterococcus faecalis (CMI este 0,008 mg/mL), Staphylococcus epidermidis
(CMI este 0,016mg/mL) și Staphylococcus aureus (CMI este 0,062 mg/mL). Rezultatele au arătat o activitate antibacteriană
semnificativă a uleiului împotriva bacteriilor Gram-pozitive și mai puțin împotriva bacteriilor Gram-negative
Effects of Specially Designed Energy-Restricted Diet on Anthropometric Parameters and Cardiometabolic Risk in Overweight and Obese Adults: Pilot Study
No full textBackground/Aims: This study examined the effects of a specially designed energy-restricted diet with alternate carbohydrate intake on body composition and cardiometabolic risk factors in overweight and obese adults. The aim was to assess whether the intervention could lead to significant weight loss, improve body composition, and reduce cardiometabolic risks. Methods: Sixty-five participants (34 women, 31 men) with an average BMI of 31.8 ± 9.1 kg/m2 (women) and 34.1 ± 6.4 kg/m2 (men) participated in a 14-week intervention. The diet included different days of carbohydrate intake and a 20% reduction in total daily energy consumption. Anthropometric measurements and biochemical parameters, including predictive indices of cardiometabolic risk, were determined at baseline and after the intervention. Results: The intervention resulted in a significant reduction in body weight (mean weight loss of 17%, p < 0.001), with 64.6% of participants achieving a weight loss of at least 10%. Muscle mass as a percentage of total body weight increased. Cardiometabolic improvements were observed in fasting blood glucose (from 5.4 to 4.9 mmol/L, p < 0.001) and LDL cholesterol (from 3.38 to 2.81 mmol/L, p < 0.001). Gender-specific differences were found, particularly in HDL-C, which decreased significantly in women (p = 0.013), while there was a non-significant increase in men. Cardiometabolic indices, including the Visceral Adiposity Index (VAI) and the Cardiometabolic Index (CMI), also improved significantly. Conclusions: The alternate carbohydrate diet improved body composition, cardiometabolic health, and treatment adherence through metabolic flexibility. However, the short duration of this study and the lack of a control group suggest that further research is needed to assess long-term sustainability
The importance of oxidative stress and the kynurenine pathway of tryptophan metabolsm in the onset and development of multiple sclerosis in the population of Serbia
No full textMultipla skleroza (MS) je autoimunska bolest, nepredvidivog toka, sa zonama inflamacije i demijelinizacije u centralnom nervnom sistemu. Cilj istraživanja je bio da se utvrdi klinički značaj oksidativnog stresa (OS) i kinureninskog puta (KP) metabolizma triptofana u nastanku i razvoju relapsno-remitentne multiple skleroze (RRMS) u populaciji Srbije, kao i efekti terapije koja menja prirodni tok bolesti (DMT). Dodatno, cilj je bio da se ispita uticaj sredinskih faktora (duvanski dim, izlaganje suncu i konzumiranje kravljeg mleka) na nastanak i razvoj MS.Istraživanje je obuhvatilo 175 RRMS pacijenata (76 muškaraca i 99 žena) i 254 zdravih osoba (81 muškarac i 173 žene). Za procenu progresije bolesti korišćen je Multiple Sclerosis Severity Score (MSSS). OS je procenjen na osnovu ukupnog antioksidativnog i oksidativnog statusa i oksidativnog indeksa u serumu (TAS, TOS, OSI) i 8-okso-7,8-dihidro-2´-deoksiguanozina (8-oksodG/kreatinin) u urinu. Analiziran je polimorfizam gena za enzim 8-oksoguanin-glikozilazu 1, OGG1 rs1052133 (Ser326Cys). U serumu pacijenata su praćeni laki lanci neurofilamenata (sNfL), sfingozin-1-fosfat (S1P), kinureninska (KA) i hinolinska (QA) kiselina.Rezultati ovog istraživanja su pokazali da OS utiče na nastanak i razvoj MS u populaciji Srbije. Porast OSI, porast 8-oksodG/kreatinina i pasivno pušenje su identifikovani kao nezavisni prediktori za nastanak MS. Dodatno, kod pacijenata sa težim oblikom MS, nivo OS povezanog sa pušenjem bio je veći kod žena, što ukazuje na veće potrebe uključivanja antioksidativne terapije kod žena koje su već obolele od MS, kako bi se prevenirao dalji nepovoljan tok bolesti. Primena TAS, TOS, OSI i 8-oksodG/kreatinina ima potencijalni značaj u proceni rizika od razvoja OS i praćenju efikasnosti antioksidativne terapije. Viši 8-oksodG/kreatinin kod nosilaca C alela rs1052133 u odnosu na GG homozigote bio je povezan sa pojavom MS, što ukazuje na povećanu izloženost sistemskim efektima OS kod nosioca određenog alela genetičke varijante OGG1 rs1052133, ali i na efikasnost sistema reparacije oksidativno modifikovane dezoksiribonukleinske kiseline (DNK). S druge strane, prisustvo C alela kod pacijenata-pušača je bilo povezano sa višim 8-oksodG/kreatinin indeksom u odnosu na nepušače, što ukazuje na moguću genotip-fenotip interakciju u razvoju OS. Dalje, rezultati ove studije ukazuju na zaštitni efekat DMT terapije od pojave OS, međutim, kod žena efekti terapije na prevenciju OS i pojavu teškog oblika MS su bili ograničeni, što ukazuje na neophodnost uvođenja antioksidativne terapije kod žena. Osim toga što su žene, generalno imale viši nivo sNfL, ova studija je pokazala da žene-nosioci G alela rs1052133 imaju viši sNfL u odnosu na žene-homozigote CC, kao i u odnosu na muškarce-nosioce G alela. Dodatno, žene su nakon šestomesečne DMT terapije imale značajno veći porast sNfL u odnosu na muškarce, što može ukazati da njihova veća osetljivost na oštećenje aksona zahteva duži vremenski period za postizanje pozitivnih efekata terapije. Povećana produkcija hinolinske kiseline bila je povezana sa rizikom od progresije MS kod žena, što ukazuje da hronična aktivacija KP povećava rizik od neurodegeneracije. Nakon šestomesečne DMT terapije, kod oba pola uočen je značajan pad indeksa QA/KA, što ukazuje na njen zaštitni efekat od nakupljanja neurotoksičnih metabolita i ovaj indeks bi mogao da bude koristan za procenu rizika od progresije MS...Multiple sclerosis (MS) is an autoimmune disease with an unpredictable course, with zones of inflammation and demyelination in the central nervous system. The aim of the research was to determine the clinical significance of oxidative stress (OS) and the kynurenine pathway (KP) of tryptophan metabolism in the onset and development of relapsing-remitting multiple sclerosis (RRMS) in the population of Serbia, as well as the effects of therapy that changes the natural course of the disease (DMT). Additionally, the aim was to examine the influence of environmental factors (tobacco smoke, sun exposure and consumption of cow's milk) on the onset and development of MS.The research included 175 RRMS patients (76 men and 99 women) and 254 healthy individuals (81 men and 173 women). The Multiple Sclerosis Severity Score (MSSS) was used to assess the severity of the disease. OS was evaluated based on total antioxidant and oxidative status and oxidative index in serum (TAS, TOS, OSI), and 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodG/creatinine) in urine. The gene polymorphism of the enzyme 8-oxoguanine-glycosylase 1, OGG1 rs1052133 (Ser326Cys) was analyzed. Neurofilament light chains (sNfL), sphingosine-1-phosphate (S1P), kynurenic (KA) and quinolinic (QA) acid were monitored in the patients' serum.The results of this research showed that OS affects the onset and development of MS in the population of Serbia. Increase in OSI, increase in 8-oxodG/creatinine and passive smoking were identified as independent predictors for the development of MS. Additionally, in patients with a more severe form of MS, the level of OS-related to smoking was higher in women, which indicates a greater need to include antioxidant therapy in women already suffering from MS, in order to prevent further adverse course of the disease. The application of TAS, TOS, OSI and 8-oxodG/creatinine has potential importance in assessing the risk of developing OS and monitoring the effectiveness of antioxidant therapy. Higher 8-oxodG/creatinine in rs1052133 C allele carriers compared to GG homozygotes was associated with the occurrence of MS, which indicates increased exposure to systemic effects of OS related to certain allele of genetic variant OGG1 rs1052133, but also the efficiency of the repair system of oxidatively modified DNA. On the other hand, the presence of the rs1052133 C allele in smoking patients was associated with higher 8-oxodG/creatinine compared to non-smokers, indicating a possible genotype-phenotype interaction in the development of OS. Furthermore, the results of this study indicate a protective effect of DMT therapy against the occurrence of OS, however, in women, the effects of the therapy on the prevention of OS and the occurrence of severe MS were limited, which indicates the necessity of introducing antioxidant therapy in women. In addition to women generally having higher sNfL, this study showed that female carriers of the rs1052133 G allele have higher sNfL compared to homozygous CC women, as well as compared to male carriers of the G allele. After six months of DMT therapy, women had a significantly greater increase in sNfL compared to men, which may indicate that their greater sensitivity to axonal damage requires a longer period of time to achieve positive effects of therapy. Increased production of quinolinic acid was associated with the risk of MS progression in women, indicating that chronic KPactivation increases the risk of neurodegeneration. After six months of DMT therapy, a significant decrease in the QA/KA index was observed in both sexes, indicating its protective effect against the accumulation of neurotoxic metabolites, and this index could be useful for assessing the risk of MS progression..