Antiproliferative and antibacterial activity of some glutarimide derivatives

Antiproliferative and antibacterial activities of nine glutarimide derivatives (1–9) were reported. Cytotoxicity of compounds was tested toward three human cancer cell lines, HeLa, K562 and MDA-MB-453 by MTT assay. Compound 7 (2-benzyl-2-azaspiro[5.11]heptadecane-1,3,7-trione), containing 12-membered ketone ring, was found to be the most potent toward all tested cell lines (IC50 = 9–27 μM). Preliminary screening of antibacterial activity by a disk diffusion method showed that Gram-positive bacteria were more susceptible to the tested compounds than Gram-negative bacteria. Minimum inhibitory concentration (MIC) determined by a broth microdilution method confirmed that compounds 1, 2, 4, 6–8 and 9 inhibited the growth of all tested Gram-positive and some of the Gram-negative bacteria. The best antibacterial potential was achieved with compound 9 (ethyl 4-(1-benzyl-2,6-dioxopiperidin-3-yl)butanoate) against Bacillus cereus (MIC 0.625 mg/mL; 1.97 × 10−3 mol/L). Distinction between more and less active/inactive compounds was assessed from the pharmacophoric patterns obtained by molecular interaction fields

Titanium(IV) oxide nanoparticles surface-modified with salicylic and 5-aminosalicylic acid affect lipid and protein oxidation in the brain of Wistar rats

13th Neuronus 2024 Neuroscience Forum Krakow, 25-27 April 2024

Estradiol receptors mediate estradiol-induced inhibition of mitochondrial Ca2+ efflux in rat caudate nucleus and brain stem

Our earlier studies found that in vitro estradiol modulates mitochondrial Ca2+ transport in discrete brain regions. The present study examined the role of estradiol receptors (ERs) in estradiol-induced inhibition of Ca2+ efflux from synaptosomal mitochondria isolated from rat caudate nuclei and brain stems. Radioactively labeled CaCl2 (0.6-0.75 mu Ci (CaCl2)-Ca-45) was used for Ca2+ transport monitoring. The results revealed that in the presence of ER antagonist 7 alpha, 17 beta-[9[(4,4,5,5,5-pentafluoropentyl) sulfinyl] nonyl] estra-1,3,5( 10)-triene-3,17-diol (ICI 182,780) (1 mu mol/L), the inhibitory effect of estradiol on mitochondrial Ca2+ efflux was more than 60% decreased, suggesting the involvement of ER in this mode of estradiol neuromodulatory action. When particular contributions of ER alpha and ER beta were tested, it was found that ER beta agonist 2,3-bis(4-hydroxy phenyl)-propionitrile (10 nmol/L) inhibited Ca2+ efflux more than 20%, while the inhibition with ER alpha agonist 4,4', 4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (10 nmol/L) was about 10%, both compared to the control. Both agonists demonstrated attenuation of Ca2+ efflux decrease in the presence of mitochondrial Na+/Ca2+ exchanger antagonist 7-chloro-5-(2-chlorophenyl)-1,5-dihyhdro-4,1-benzothiazepin-2(3H)-one (10 mu mol/L), showing interference with the inhibitory action of that agent. Our results strongly indicate ERs as the mediators of estradiol-induced mitochondrial Ca2+ efflux inhibition in rat caudate nucleus and brain stem synaptosomes

Cytogenetic findings in Serbian patients with Turner's syndrome stigmata

Cytogenetic findings are reported for 31 female patients with Turner's syndrome. Chromosome studies were made from lymphocyte cultures. Non-mosaicism 45, X was demonstrated in 15 of these patients, whereas only three were apparently mosaic. Eight patients showed non-mosaic and four patients showed mosaic structural aberrations of the X-chromosome. One non-mosaic case displayed a karyotype containing a small marker chromosome. Conventional cytogenetics was supplemented by fluorescence in situ hybridization (FISH) with an X-specific probe to identify the chromosomal origin of the ring and a 1q12-specific DNA probe to identify de novo balanced translocation (1;9) in one patient. To our knowledge, this is the first finding of karyotype 45,X,t(1;9) (cen;cen)/46,X,r(X),t(1;9)(cen;cen) in Turner's syndrome. The same X-specific probe was also used to identify a derivative chromosome in one patient

Effect of Sex Hormones on Plasma Phospholipid Fatty Acid Composition in Intact Rats and Rats With Bilaterally Occluded Carotid Arteries

The effects of 8-days treatment with 17 alpha-estradiol (33.3 mu g/kg) and progesterone (1.7 mg/kg) on plasma lipids and fatty acid composition of plasma phospholipids were examined in intact (INT) and bilaterally common carotid arteries occluded (BCO) male Wistar rats. Significant decrease of triglyceride level was found in BCO rats after the estradiol treatment. Both hormones elevated proportion of 18:1n-7 fatty acid in INT, but they failed to have such an effect in BCO. Estradiol increased 22:5n-3 and total n-3 polyunsaturated fatty acids (PUFA) in intact, and decreased 18:2n-6 in BCO rats. Significantly lower level of total n-3 was found in progesterone-treated than in estradiol-treated BCO rats. Given that n-3 PUFA have many beneficial effects on cell and tissue function, while n-6 PUFA have mostly the opposite effects, estradiol, rather than progesterone, was seen to improve plasma lipids and phospholipids FA profiles in INT and BCO animals. Estradiol significantly elevated the estimated activity of Delta 9-desaturases and progesterone of Delta 5-desaturase in BCO group, with no effects in INT rats

Antioxidant Enzymes in Blood of Women With Uterine Hyperplasia

The literature emphasizes the involvement of oxidative stress in the etiopathogenesis of many uterine diseases. Antioxidant system (AOS) represents the protective mechanism used by cells to neutralize overproduced reactive oxygen species (ROS) and prevent oxidative stress. We have previously shown that in gynecological patients with various diagnoses, the reproductive and other factors may be associated with antioxidant capacity and the ability to defend against oxidative damage. In this study, we examined the changes in expression of antioxidant enzymes (AOE): superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) in the blood of women with endometrial hyperplasia. Our results indicate that hyperplasia induces perturbance in oxidative balance, particularly in glutathione redox cycle enzymes

Comparable Toxicity of Surface-Modified TiO2 Nanoparticles: An In Vivo Experimental Study on Reproductive Toxicity in Rats

Nanoparticles (NPs), a distinct class of particles ranging in size from 1 to 100 nm, are one of the most promising technologies of the 21st century, and titanium dioxide NPs (TiO2 NPs) are among the most widely produced and used NPs globally. The increased application of TiO2 NPs raises concerns regarding their global safety and risks of exposure. Many animal studies have reported the accumulation of TiO2 NPs in female reproductive organs; however, evidence of the resultant toxicity remains ambiguous. Since the surface area and chemical modifications of NPs can significantly change their cytotoxicity, we aimed to compare the toxic effects of pristine TiO2 powder with surface-modified TiO2 powders with salicylic acid (TiO2/SA) and 5-aminosalicylic acid (TiO2/5-ASA) on the ovaries, oviducts, and uterus on the 14th day following acute oral treatment. The results, based on alterations in food and water intake, body mass, organ-to-body mass ratio, hormonal status, histological features of tissues of interest, and antioxidant parameters, suggest that the modification with 5-ASA can mitigate some of the observed toxic effects of TiO2 powder and encourage future investigations to create NPs that can potentially reduce the harmful effects of TiO2 NPs while preserving their positive impacts

TiO2 nanoparticles and TiO2 nanoparticles surface modified with salicylic acid affect neurological functions and oxidative stress markers in the eyes of adult rats

Titanium dioxide nanoparticles (TiO2NPs) are widely used in pharmaceutics, food products and cosmetics. Besides numerous beneficial outcomes, they also induce toxic effects in different organs, including the eyes. The recent findings report that some surface modifications can attenuate TiO2NPs toxicity. Thus, the aim of this study was to compare the effects of acute oral treatment with commercially available, bare TiO2NPs and TiO2NPs surface modified with salicylic acid (SA-TiO2NPs) using adult Wistar rats as model organisms. Control animals were gastrically intubated with vehicle (0.01 M HCl), while others were treated with either TiO2NPs or SA-TiO2NPs (1000mg/kg dissolved in vehicle). Afterward, the mortality rate as the acute toxicity parameter and parameters of neurological function were assessed. Animals were sacrificed on the 14th day following treatment. In the eye crude synaptosomal fraction, the effects of treatments on oxidative stress markers such as prooxidant/antioxidant balance (PAB) and lipid peroxidation (LPO) were compared. According to the obtained results, the mortality was 0 in all experimental groups. TiO2NPs and SA-TiO2NPs treatments displayed mild effects on spontaneous activity and pacing and had no impact on the visual placing reflex. Moreover, TiO2NPs and SA-TiO2NPs exposure significantly elevated PAB levels, when compared to controls. Animals treated with SA-TiO2NPs had similar LPO levels as controls, while in TiO2NPs group LPO levels were significantly increased. The presented data showed that both examined nanoparticles exerted similar outcomes referring to most of the investigated parameters, however, surface binding of SA decreased the level of LPO and thus, mitigated some of TiO2NPs toxicity in the eyes.ICCBIKG 2023 : 2nd International Conference on Chemo and Bioinformatics, September 28-29, 2023; Kragujeva

Modeling and simulation of hydraulic buffering valve for power-shift transmission

Introduction/purpose: The hydraulic buffering valve has the greatest influence on the dynamic characteristics of power-shift transmission. The hydraulic buffering valve is a transmission element that controls increase in pressure in friction assemblies during the gear shifting process. By choosing the optimal control of pressure increase during shifting, reduction of dynamic loads in gear transmissions and thermal loads in friction assemblies is achieved. Methods: The paper analyzes the principle of one of hydraulic buffering valve solutions as well as the influence of certain parameters on the control of pressure increase. After the analysis of the working principle of the hydraulic buffering valve, a simulation model was developed in the MATLAB/Simulink software package. Results: The results obtained using the simulation model were compared with the experimental results of the selected pressure modulator solution. The selected hydraulic buffering valve was developed as part of the development of a device for power-shift transmission. The simulation results showed a satisfactory match with the experimental results. Conclusion: The developed simulation model enables a relatively easy and quick change of the parameters of the hydraulic buffering valve as well as a possibility of a faster and better understanding of the influence of individual parameters on pressure increase during the gear shifting process