Search

The cytochrome P450 superfamily consists of hemeproteins involved in the detoxication of different xenobiotics, including drugs. The CYP2 gene family is responsible for the metabolism of 80% of the drugs in clinical use. There are considerable interindividual and interethnic variabilities in the rate of drug metabolism as a result of genetic polymorphisms. The goal of our study was to determine the frequency of 10 genetic polymorphisms in CYP2 family genes to give light on the pharmacogenetic defects of the main CYPs, involved in drug metabolism, in Bulgarian individuals. We detected high allele frequency for CYP2D6*10 (0.27), CYP2D6*4 (0.22), and CYP2B6*9 (0.24), followed by CYP2C19*2 (0.14), CYP2C9*3 (0.11) and CYP2C9*2 (0.09). The genotype frequencies were also determined for all investigated variants. In total 47.2% of the analyzed individuals carried CYP2D6 genetic polymorphisms – 5.6% carried a single variant and 41.6% were found to have two or more such variants. Homozygotes for CYP2D6 variants were established among 14% of Bulgarian individuals. Determination of the prevailing pharmacogenetic polymorphisms of the CYPs, most responsible for drug metabolism, will lead to a lower risk of drug toxicity, increased drug efficacy, and drug dose optimization. more...

Background: Probiotics have been used to prevent antibiotic-associated diarrhea (AAD), but practical guidelines are sparse. This trial evaluated the efficacy and safety of a high-dose, multistrain probiotic mix (Sinquanon), specially designed for prevention of AAD in adults., Methods: A phase IV, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted over 5 months. Participants receiving broad-spectrum antibiotics were administered the specialized probiotic mix or placebo from the first dose of antibiotics until 14 days after the last antibiotic dose. The primary outcome measure was the incidence of AAD., Results: In total, 564 participants were randomized (probiotic mix: 285; placebo: 279), of which 9 participants discontinued the trial early (probiotic mix: 3; placebo: 6), had no efficacy data, and were excluded from the efficacy analysis. The 555 remaining participants completed the trial and were included in the efficacy analysis (probiotic mix: 282; placebo: 273). AAD occurred less frequently in the studied probiotic mix versus placebo group (9.2% vs 25.3%, P < .001), resulting in an absolute risk reduction of 16% and a number needed to treat of 6 (95% confidence interval, 4.55-10.49). A significant improvement in the average gastrointestinal quality of life in the studied probiotic mix versus placebo group was also observed. There were no clinically relevant differences in the incidence of adverse events between the studied probiotic mix and the placebo group., Conclusions: The specially designed high-dose, multistrain probiotic mix (Sinquanon) demonstrated to be beneficial compared with placebo in the prevention of AAD in adults who received broad-spectrum antibiotics., Clinicaltrialsgov Identifier and Url: NCT05607056; https://classic.clinicaltrials.gov/ct2/show/NCT05607056., Competing Interests: Potential conflicts of interest. All authors have delivered scientific lectures on a given problem for various pharmaceutical companies, including Neopharm Bulgaria., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.) more...

Introduction: The current understanding of the biological impacts of a static magnetic field (SMF) is restricted to the direct interactions of the magnetic field with biological membranes. The electrokinetic (zeta) potential is an electrochemical property of erythrocyte surfaces which was negatively charged in physiological media after SMF exposure (0.1‒2.0 T). Methods: The novel data about electrokinetic parameters of the erythrocytes is determined by microelectrophoresis after SMF-exposure in norm and heterozygous β-thalassemia. The methods of light scattering, lipid peroxidation, fluorescence microscopy are used. Results: The electrokinetic potential of erythrocytes in norm is increased after SMF intensities due to enhanced negatively exposed charges on the outer surface of the membrane accompanied by an increase in light scattering where changes in cell morphology are observed. Conversely, a decrease in the zeta potential of β-thalassemia erythrocytes upon SMF-treatment was determined because of the reduction in the surface electrical charge of the membranes, where a significant decrease in light scattering at 1.5 T and 2.0 T was recorded. Exposure to SMF (0.5-2.0 T) was associated with an increase in the malondialdehyde content in erythrocytes. Biophysical studies regarding the influence of SMF on the electrostatic free energy of cells shows an increase in negative values in healthy erythrocytes, which corresponds to the implementation of a spontaneous process. This is also the process in β-thalassemia cells after SMF exposure with lower negative values of free electrostatic energy than erythrocytes in norm. Discussion: The effect of static magnetic field (SMF 0.1-2.0 T) on the electrokinetic and morphological characteristics of erythrocytes in norm and β-thalassemia is determined and correlated with the increase/reduction in surface charge and shrinkage/swelling of the cells, respectively. Lipid peroxidation of healthy and β-thalassemia erythrocytes caused an enhancement of lipid peroxidation because of the higher concentrations of TBARS products in cellular suspension. SMF (0.1‒2.0 T) altered the spontaneous chemical processes with negative values of electrostatic free energy of erythrocytes in norm and β-thalassemia accompanied by a lower FITC-Concanavalin A binding affinity to membrane receptors (SMF 2.0 T). The electrokinetic properties of human erythrocytes in norm and β-thalassemia upon SMF treatment and their interrelationship with the structural-functional state of the membrane were reported. The presented work would have future fundamental applications in biomedicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Doltchinkova, Lozanova, Rukova, Nikolov, Ivanova and Roumenin.) more...

Vitamin D plays a role in regulating immune homeostasis, inflammation and has an impact on the pathogenesis of inflammatory bowel diseases (IBD). IBD has a multifactorial pathogenesis primarily associated with immune dysregulation, dysbiosis, structurally altered intestinal mucosa, and genetic factors. The immunomodulatory function of this vitamin is linked to its control over innate and adaptive immunity, facilitated through its nuclear vitamin D receptor, leading to the inhibition of nuclear factor kappa-B. This study aimed to investigate serum vitamin D levels in patients with IBD compared to healthy individuals and to evaluate the relationship between vitamin D and inflammatory markers. Cross-sectional study. The study included 106 participants divided into 2 groups: patients with IBD (92), and healthy controls (14). The diagnosis of IBD was based on clinical, laboratory, fecal, endoscopic, and histological findings, following the European guidelines for diagnosis and follow-up ECCO-ESGAR guidelines for diagnostic assessment of IBD from 2019. Serum vitamin D levels were measured along with laboratory tests, imaging, and endoscopic examinations. IBD activity was evaluated using the Montreal classification and clinical and endoscopic indices. Data analysis involved calculating the mean, minimum, and maximum values, standard deviation, and Pearson coefficient. The level of statistical significance for this study was set at P < .05. The study found a prevalence of vitamin D deficiency in 32.6% of patients with IBD, while 66.3% had insufficiency, as compared with healthy individuals. The mean levels of vitamin D in UC and CD were 16 ± 8.6 ng/mL, whereas in the control healthy group, they were 26 ± 9.73 ng/mL. A statistically significant reverse correlation was observed between lower vitamin D levels and higher levels of the inflammatory markers. The study concluded that IBD patients exhibit lower levels of vitamin D, which is associated with inflammation and may contribute to the pathogenesis of the disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.) more...

Background and Aims: We investigated the effect of WAY-163909, a novel 5-hydroxytryptamine selective 2C receptor agonist on body weight, blood glucose levels, and insulin resistance in obese and diabetic Wistar rats., Materials and Methods: We used twenty male Wistar rats with obesity and obesity-induced diabetes and twenty healthy Wistar rats as a control group. Each of these groups was separated into two subgroups: one with a daily intraperitoneal application of WAY-163909 (1 mg/kg) and one without. During the study, body weight, blood glucose levels, and immunoreactive insulin were tracked., Results: A reduction of 5.5% ( p < 0.05) in body weight was registered in the rat group with diabetes and obesity and 2.56% in the control group with a daily application of WAY-163909 (1 mg/kg) at the end of the study. Decreases of 35.4% in blood glucose levels at week four in the diabetic and obese rat group with a daily application of WAY-163909 (1 mg/kg) were registered. A reduction of insulin levels of 4.1% ( p < 0.05) in the diabetic and obese rats group using WAY-163909 was also observed., Conclusion: In our study, using WAY-163909 (1 mg/kg) led to a reduction of blood glucose levels, immunoreactive insulin, and body weight. more...

Pooled Immunoglobulin G (IgG), hematin and the membrane-disruptive amphipathic peptide melittin have received attention as powerful biomacromolecules for biomedical and pharmacology applications. Their action on surface properties, oxidation status and epifluorescence properties measured in vitro provide useful information about the functional activity of upper biomacromolecules in erythrocytes in vivo. The hemolysis of erythrocyte membranes, as well as changes in hematocrit and the morphology of erythrocytes, was investigated here via fluorescence microscopy using FITC-concanavalin A binding to cells. The effect of melittin on the membrane capacitance and resistance of model lipid bilayers was probed via electrochemical impedance spectroscopy. Lipid bilayer capacitance was higher in the presence of 0.10 g/L melittin compared to that in the control, which is likely related to bilayer thinning and alterations of the dielectric permittivity of melittin-treated membranes. The biomolecule interactions with red blood cells were probed in physiological media in which the surface of erythrocyte membranes was negatively charged. Surface parameters of erythrocytes are reported upon IgG/hematin and IgG/melittin treatment. Pooled IgG in the presence of melittin, preincubated IgG/hematin preparations promoted a significant decrease in the electrokinetic potential of erythrocytes (Rh-positive). A malondialdehyde (MDA) assay revealed a high rate of lipid peroxidation in erythrocytes treated with IgG/hematin or IgG/melittin preparations. This finding might be a result of pooled IgG interactions with the hematin molecule and the subsequent conformational changes in the protein molecule altering the electrokinetic properties of the erythrocyte membrane related to the Rh group type of erythrocytes. The pooled IgG and hematin are reported to have important consequences for the biophysical understanding of the immunopathological mechanisms of inflammatory, autoimmune and antibody-mediated pathological processes. more...

This study evaluates some of the neuromodulatory mechanisms of the memory loss preventive effect of alpha-lipoic acid (ALA) in a scopolamine (Sco)-induced rat model of Alzheimer's disease (AD) type dementia. Our results confirmed that Sco administration induces significant memory impairment, worsens exploratory behaviour and habituation, increases acetylcholinesterase (AChE) activity, and induces pathological monoamine content changes in the prefrontal cortex and hippocampus. ALA administration largely prevented Sco-induced memory impairment. It also improved exploratory behaviour and preserved habituation, and it decreased AChE activity, reversing it to control group levels, and corrected aberrant monoamine levels in the prefrontal cortex and hippocampus. According to the data available, this is the first time that ALA-induced changes in AChE and monoamine levels in the prefrontal cortex and hippocampus (brain structures related to learning and memory) have been demonstrated in a Sco-induced rat model of AD type dementia., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...