Effect of captopril on serum lipid levels and cardiac mitochondrial oxygen consumption in experimentally-induced hypercholesterolemia in rabbits

Angiotensin converting enzyme inhibitors are widely used in therapy of cardiovascular diseases. However, the consensus on effects of these inhibitors in control of myocardial oxygen consumption during the process of experimental hypercholesterolemia and under the condition of endothelial dysfunction has not been reached. Here we examined effects of captopril, an angiotensin converting enzyme inhibitor, on serum lipid levels and oxygen consumption rate in mitochondria isolated from heart of rabbits treated by hypercholesterolemic diet. During the twelve-week period, the Chinchilla male rabbits were daily treated by saline (controls); 1 % cholesterol diet; 5 mg/kg/day captopril or 1 % cholesterol + 5 mg/kg/day captopril. Total- and high-density lipoprotein cholesterol and triglyceride in serum were measured spectrophotometricly. The left ventricle mitochondrial fraction was isolated and myocardial oxygen consumption was measured by Biological Oxygen Monitor. Mitochondria isolated from hearts of rabbits exposed to hypercholesterolemic diet showed significantly reduced respiration rates (state 3 and state 4) with altering adenosine diphosphate/oxygen ratio, whereas the respiratory control ratio was not affected when compared to controls. Mitochondria from cholesterol/captopril-treated animals showed significantly reduced respiration rates without altering adenosine diphosphate/oxygen ratio index or respiratory control ratio. Although captopril did not exert the favorable effect on serum lipid levels in cholesterol-treated animals, it restored the mitochondrial oxygen consumption. Further studies should be performed to define the underlying physiological and/or pathophysiological mechanisms and clinical implications

Alcohol abuse and alcohol depen

Abstract Alcoholism results from an interplay between genetic and environmental factors, and is linked to brain defects and associated cognitive, emotional, and behavioral impairments. A confluence of findings from neuroimaging, physiological, neuropathological, and neuropsychological studies of alcoholics indicate that the frontal lobes, limbic system, and cerebellum are particularly vulnerable to damage and dysfunction. An integrative approach employing a variety of neuroscientific technologies is essential for recognizing the interconnectivity of the different functional systems affected by alcoholism. In that way, relevant experimental techniques can be applied to assist in determining the degree to which abstinence and treatment contribute to the reversal of atrophy and dysfunction. Keywords Alcoholism . Frontal lobes . Limbic system . Cerebellum . Right hemisphere Alcoholic beverages contain ethanol, a psychoactive drug with relaxant and euphoric effects, consumed by people throughout the world. In general, the effects of alcohol intoxication follow a biphasic time course as the initial feelings of relaxation and exuberance give way to hangover, exhaustion, and depression, or vomiting and loss of consciousness in cases of higher doses (Nagoshi and Wilson 1989). Criteria for classifying someone as an alcoholic vary Risky drinking patterns for men are defined as consuming more than 14 drinks per week, or more than four drinks in a single day at least once a month; for women, the limits are more than seven drinks per week and three drinks per da

CD22 regulates early B cell development in BOB.1/OBF.1-deficient mice

BOB.1/OBF1 (also called OCA-B), a B lymphocyte-specific transcriptional coactivator, is recruited to octamer-containing promoters by interacting with the Oct-1 or Oct-2 proteins. BOB.1/OBF.1-deficient mice show impaired secondary immunoglobulin isotype secretion and complete absence of germinal centers. Furthermore, numbers of splenic B cells are reduced due to a developmental block at the transitional B cell stage in the bone marrow. We found that surface expression of CD22 is selectively increased on B lineage cells in the bone marrow of BOB.1/OBF.1-deficient mice. CD22 is known as a negative regulator of B cell receptor signaling. We therefore investigated whether defects in B cell development in the BOB.1/OBF1-deficient mice might be due to CD22 up-regulation. Mice were generated lacking both genes. In BOB.1/OBF.1 xCD22 double-deficient mice, numbers of transitional B cells in the bone marrow were normal. Consequently, double-deficient mice also had normal B to T cell ratios in the spleen. We show that BOB.1/OBF.1(-/-) B cells were incapable to induce BCR-triggered Ca2+ mobilization. This Ca2+-signalling defect was restored in BOBA/ OBF1 xCD22 double-deficient B cells. Nevertheless, double-deficient animals were unable to mount humoral immune responses and to form germinal centers. Finally, we demonstrate that CD22(-/-) splenic B cells proliferate independently of BOB.1/OBF1 upon stimulation with LPS. These studies suggest that the B cell differentiation defect observed in BOB.1/OBF.1(-/-) mice is BCR-signal dependent. However, the impairment in germinal center formation is caused by a different mechanism

Uticaj supstituenata na IR, 1H- i 13C-NMR spektralne podatke N-(supstituisanih fenil)-2-cijanoacetamida - korelaciona analiza

Linear free energy relationships (LFER) were applied to the IR, H-1- and C-13-NMR spectral data of N-(substituted phenyl)-2-cyanoacetamides. A variety of substituents were employed for phenyl substitution and fairly good correlations were obtained using the simple Hammett and the Hammett-Taft dual substituent parameter equations. The correlation results of the substituent induced C-13-NMR chemical shifts (SCS) of the Cl, C=O and N-H atom indicated different sensitivity with respect to electronic substituent effects. A better correlation of the SCSc=O with a combination of electrophllic and nucleophilic substituent constants indicated a significant contribution of extended resonance interaction (pi-delocalization) within the pi(1)-unit. The conformations of the investigated compounds were studied using the OFT B3LYP/6-311G** method and, together with the results of C-13-NMR and IR spectroscopic studies, a better insight into the influence of such a structure on the transmission of electronic substituent effects was obtained.Principi linearnih korelacija slobodnih energija (LFER) su primenjeni na IR, 1H- i 13C-NMR spektralne podatke N-(supstituisanih fenil)-2-cijanoacetamida. Pri sintezi N-(supstituisanih fenil)-2-cijanoacetamida izvršen je zadovoljavajući izbor supstituenata u pogledu elektronskih svojstava kako bi se adekvatno sagledao uticaj elektronskih efekata supstituenata na pomeranja u IR, 1H- i 13C-NMR spektralnim podacima. Primenom proste Hametove jednačine dobijene su zadovoljavajuće korelacije. Na osnovu korelacionih rezultata uočen je primaran uticaj elektronskih efekata na SCS (supstituentom indukovana hemijska pomeranja) vrednosti N-H vodonika, C1 i C=O ugljenika ispitivanih jedinjenja. Korelacioni rezultati za C=O ugljenik se značajno popravljaju ako se koristi kombinacija Ϭ+ i Ϭ- konstanti supstituenata, takozvane elektrofilne i nukleofilne konstante supstituenata, što ukazuje na postojanje značajne proširene rezonancione interakcije supstituenata i elektronske gustine karbonilne grupe. Vrednosti konstanti proporcionalnosti pF i pR za sve atome, ukazuju na približno isti doprinos efekta polja i rezonancionog efekta supstituenata. Efekat polja je nešto izraženji na N-H vodoniku, i za sve atome pokazuje značajne razlike u odnosu na njihov položaj u molekulskoj strukturi ispitivanih jedinjenja. Uticaj efekata supstituenata na IR vibracije istezanja N-H (simetrične i antisimetrične), C=O i CN veze je prevashodno elektronske prirode što se može zaključiti na osnovu dobrih korelacija dobijenih primenom Hametove jednačine i Ϭ parametara supstituenata. Osim toga izvršena je optimizacija geometrije ispitivanih jedinjenja primenom DFT B3LYP/ 6-311G**metode, pri čemu je nađeno da je trans-izomer nešto stabilnji, izuzev u slučaju jedinjenja 3. Supstituisana fenil-grupa i amidna grupa, kod trans-izomera, su približno koplanarne, dok se kod cis- izomera uočava značajna devijacija koja je značajno određena elektronskim efektima prisutnog supstituenta. Takođe je ispitivan položaj cis/trans ravnoteže u ugjen-tetrahloridu, i na osnovu rezultata FT/R analize, kada je prisutan H, CH3, OCH3, Br, i COOH supstituent, nađeno je da je cis izomer u velikom višku, a za ostala jedinjenja utvrđeno je postojanje ravnoteže cis- i trans-izomera

Supplementary data for article: Ajaj, I. A.; Mijin, D.; Maslak, V.; Brkovic, D.; Milčić, M. K.; Todorović, N.; Marinković, A. A Simple and Convenient Synthesis of Tautomeric (6 or 2)-Hydroxy-4-Methyl-(2 or 6)-Oxo-1-(Substituted Phenyl)-(1,2 or 1,6)-Dihydropyridine-3-Carbonitriles. Monatshefte Fur Chemie 2013, 144 (5), 665–675. https://doi.org/10.1007/s00706-012-0911-5

Supplementary material for: [https://doi.org/10.1007/s00706-012-0911-5]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1587

Supplementary data for article: Ajaj, I.; Markovski, J.; Rančić, M.; Mijin, D.; Milčić, M.; Jovanović, M.; Marinković, A. Solvent and Structural Effects in Tautomeric 2(6)-Hydroxy-4-Methyl-6(2)-Oxo-1-(Substituted Phenyl)-1,2(1,6)-Dihydropyridine-3-Carbonitriles: UV, NMR and Quantum Chemical Study. Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy 2015, 150, 575–585. https://doi.org/10.1016/j.saa.2015.05.055

Supplementary material for: [https://doi.org/10.1016/j.saa.2015.05.055]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1971

Supplementary material for the article: Rančić, M. P.; Stojiljković, I.; Milošević, M.; Prlainović, N.; Jovanović, M.; Milčić, M. K.; Marinković, A. D. Solvent and Substituent Effect on Intramolecular Charge Transfer in 5-Arylidene-3-Substituted-2,4-Thiazolidinediones: Experimental and Theoretical Study, 2016. https://doi.org/10.1016/j.arabjc.2016.12.013

Supplementary material for: [https://doi.org/10.1016/j.arabjc.2016.12.013]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/305

Supplementary data for article: Matijević, B. M.; Vaštag, T. T.; Apostolov, S. L.; Milčić, M. K.; Marinković, A. D.; Petrović, S. D. N-(Substituted Phenyl)-2-Chloroacetamides: LSER and LFER Study, 2015. https://doi.org/10.1016/j.arabjc.2015.09.008

Supplementary material for: [https://doi.org/10.1016/j.arabjc.2015.09.008]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/293

Supplementary data for the article: Marković, J. M.; Trišović, N. P.; Tóth-Katona, T.; Milčić, M. K.; Marinković, A. D.; Zhang, C.; Jákli, A. J.; Fodor-Csorba, K. A Structure-Property Relationship Study of Bent-Core Mesogens with Pyridine as the Central Unit. New Journal of Chemistry 2014, 38 (4), 1751–1760. https://doi.org/10.1039/c3nj01430d

Supplementary material for: [https://doi.org/10.1039/c3nj01430d]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1518

Supplementary data for the article: Božić, A. R.; Bjelogrlić, S. K.; Novaković, I. T.; Filipović, N. R.; Petrović, P. M.; Marinković, A. D.; Todorović, T. R.; Cvijetić, I. N. Antimicrobial Activity of Thiocarbohydrazones: Experimental Studies and Alignment-Independent 3D QSAR Models. ChemistrySelect 2018, 3 (7), 2215–2221. https://doi.org/10.1002/slct.201702691

Supplementary material for: [https://doi.org/10.1002/slct.201702691]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2094