PubMed Health⌕ Search

Biomedical subjects

F Devínsky

Publications and source records attributed to F Devínsky.

At least 19 recordsLinked to original sources
PubMed2005

Influence of N-dodecyl-N,N-dimethylamine N-oxide on the activity of sarcoplasmic reticulum Ca(2+)-transporting ATPase reconstituted into diacylphosphatidylcholine vesicles: efects of bilayer physical parameters.

Sarcoplasmic reticulum Ca-transporting ATPase (EC 3.6.1.38) was isolated from rabbit white muscle, purified and reconstituted into vesicles of synthetic diacylphosphatidylcholines with monounsaturated acyl chains using the cholate dilution method. In fluid bilayers at 37 degrees C, the specific activity of ATPase displays a maximum (31.5+/-0.8 IU/mg) for dioleoylphosphatidylcholine (diC18:1PC) and decreases progressively for both shorter and longer acyl chain lengths. Besides the hydrophobic mismatch between protein and lipid bilayer, changes in the bilayer hydration and lateral interactions detected by small angle neutron scattering (SANS) can contribute to this acyl chain length dependence. When reconstituted into dierucoylphosphatidylcholine (diC22:1PC), the zwitterionic surfactant N-dodecyl-N,N-dimethylamine N-oxide (C12NO) stimulates the ATPase activity from 14.2+/-0.6 to 32.5+/-0.8 IU/mg in the range of molar ratios C12NO:diC22:1PC=0/1.2. In dilauroylphosphatidylcholines (diC12:0PC) and diC18:1PC, the effect of C12NO is twofold-the ATPase activity is stimulated at low and inhibited at high C12NO concentrations. In diC18:1PC, it is observed an increase of activity induced by C12NO in the range of molar ratios C12NO:diC18:1PC< or =1.3 in bilayers, where the bilayer thickness estimated by SANS decreases by 0.4+/-0.1 nm. In this range, the 31P-NMR chemical shift anisotropy increases indicating an effect of C12NO on the orientation of the phosphatidylcholine dipole N(+)-P- accompanied by a variation of the local membrane dipole potential. A decrease of the ATPase activity is observed in the range of molar ratios C12NO:diC18:1PC=1.3/2.5, where mixed tubular micelles are detected by SANS in C12NO+diC18:1PC mixtures. It is concluded that besides hydrophobic thickness changes, the changes in dipole potential and curvature frustration of the bilayer could contribute as well to C12NO effects on Ca(2+)-ATPase activity.

Animals↗
PubMed2005

Effects of N-alkyl-N,N-dimethylamine-N-oxides on the activity of purified sarcoplasmic reticulum Ca(2+)-transporting ATPase.

N-alkyl-N,N-dimethylamine-N-oxides (CnNO, n = 10-20 is the number of alkyl carbon atoms) stimulate the skeletal sarcoplasmic reticulum (SR) Ca(2+)-transporting ATPase activity at low concentrations and inhibit it at high concentrations. The minimum concentration (cmin), at which CnNO inhibits the ATPase, continuously decreases up to n = 16-18 and then increases. The values of Cmin are smaller than the CnNO critical micelle concentration (cmc) for C10NO-C14NO homologs, but larger than cmc for C18NO-C20NO homologs. The ATPase inhibition is caused by the CnNO-induced lipid bilayer structural perturbation in the ATPase annular region, modulated by the partition equilibria of the CnNO molecules between the bilayer and aqueous phase for short alkyl chain (n = 10-16) CnNO homologs, and between the bilayer, micelles and aqueous phase for long alkyl chain (n = 18-20) CnNO homologs.

Animals↗
PubMed2004

[Catalytic activity of butyrylcholinesterase in biodegradation of organic ammonium salts in vitro].

Organic ammonium salts of N-(2-benzoyloxyethyl)-alkyldimethylammonium bromide (BCHn-1) type are formed by the homological series Ar-COO(CH2)2-N+(CH3)2CnH2a + 1.Br-, whose structure contains a biodegradably labile ester bond, on the basis of which they rank among disinfectants and antiseptics of soft character. They are preferentially biotransformed hydrolytically to produce benzoic acid and substituted choline. The rapidity of enzymatic hydrolysis depends on the chemical structure (the length of the aliphatic chain on the ammonium nitrogen), it increases up to the number of 10 nitrogens of the aliphatic chain, and it rapidly decreases with further prolongation. The paper aimed to demonstrate the catalytic activity of butyrylcholinesterase on the enzymatic hydrolysis of selected organic ammonium salts in the medium of the microsomal fraction of the rat liver on the basis of inhibitory kinetic studies with physostigmine, a cholinesterase inhibitor. The product of enzymatic hydrolysis of BCHn-1, benzoic acid, was determined after extraction with chloroform from the acid medium by means of HPLC analysis with the use of the internal standard p-iodobenzoic acid at the wavelength of 228 nm. Kinetic parameters K(M) and VMAX were evaluated following Lineweaver-Burke using the method of linear regression analysis. The specific activity of butyrylcholinesterase (E.C.3.1.1.8) in the enzymatic hydrolytic process of BCHn-1 was significantly influenced by the presence of physostigmine, which was manifested by increased K(M), KI, and IC50 values in the investigated enzymatic process of selected substrates of the homological series BCHn-1, and by decreased VMAX and rate constants.

Animals↗
PubMed2003

[Solubilization of unilamellar egg yolk phosphatidylcholine liposomes by N-alkyl-N,N-dimethylamine N-oxides].

The solubilization of extruded (100 nm) unilamellar egg yolk phosphatidylcholine (EYPC) liposomes by a series of N-alkyl-N,N-dimethylamine N-oxides (CnNO, n = 10-14 carbon atoms in the alkyl substituent) was studied using turbidimetry. The solubilizing concentration of CnNO (cS) was estimated as the CnNO concentration causing the half-maximum decrease in turbidance. From the linear cS dependence on EYPC concentration, the lipid--aqueous phase molar partition coefficient (Kp) and the CnNO:EYPC molar ratio in the CnNO + EYPC aggregates (nL:nEYPC) at cS were obtained: Kp = 82 +/- 25 and nL:nEYPC = 0.70 +/- 0.20 for C10NO, Kp = 507 +/- 215 and nL:nEYPC = 0.60 +/- 0.16 for C12NO, and Kp = 12357 +/- 93 and nL:nEYPC = 1.13 +/- 0.01 for C14NO. The value of Gibbs free energy of CnNO alkyl methylene group transfer from the aqueous to the lipid phase calculated from the Kp dependence on n is -1.2 +/- 0.2 RT (R = gas constant, T = absolute temperature), within the experimental error being the same as -1.026 +/- 0.006 RT obtained from the critical micellar concentrations of CnNO. The increased value of nL:nEYPC for C14NO is caused by the decreased hydrophobic mismatch of CnNO and EYPC hydrocarbon chain lengths. This mismatch results in a structural defect in the bilayer hydrophobic core, the primary cause of bilayer destabilization and solubilization.

Chemical Phenomena↗
PubMed2001

X-ray diffraction and neutron scattering studies of amphiphile-lipid bilayer organization.

The lipid bilayer thickness d(L), the transbilayer distance of lipid phosphate groups d(pp/inf> and the lipid surface area A(L) of fluid hydrated bilayers of lamellar phases of egg phosphatidylcholine or dipalmitoylphosphatidylcholine containing N-alkyl-N,N-dimethylamine N-oxides (CnNO), 1,4-butanedi-ammonium-N,N'-dialkyl-N,N,N',N'-tetramethyl dibromides (GSn) or mono-hydrochlorides of [2-(alkyloxy)phenyl]-2-(1-piperidinyl)ethylesters of carbamic acid (CnA) were obtained by X-ray diffraction, and the bilayer thickness in extruded unilamellar dioleoylphosphatidylcholine vesicles containing C12NO was obtained by the neutron scattering. The values of d(L), d(pp/inf> and A(L) change linearly up to the 1:1 amphiphile:lipid molar ratio. The slopes of these dependencies increase for d(L) and d(pp/inf> and decrease for AL) with an increasing number of carbons n in the amphiphile long hydrocarbon substituent (18> or =n> or =8 for CnNO, 16> or =n> or =9 for GSn, 12> or =n> or =5 for CnA), while the opposite trends are observed for the short substituent (8> or =n>/=6 for CnNO, 9> or =n> or =7 for GSn, 5> or =n> or =3 for CnA). In case of long substituents, the effects on dL), dpp/inf> and AL) are caused by the decrease in the difference between the lipid and amphiphile hydrocarbon chain lengths and by the increase in their van der Waals attraction. The short substituent amphiphiles are mobile and exchange between multiple binding sites in the bilayer, minimizing the bilayer surface area.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

Aggregation Properties of Sodium Hyaluronate with Alkanediyl-alpha,omega-bis(dimethylalkylammonium Bromide) Surfactants in Aqueous Sodium Chloride Solution.

Aggregation properties of sodium hyaluronate (NaHA) with alkanediyl-alpha,omega-bis(dimethylalkylammonium bromide) surfactants (referred to as dimeric surfactants) in aqueous sodium chloride solutions have been studied as a function of surfactant chemical structure. Surface tension measurements indicate the unusual parabolic dependence of surface tension vs log surfactant concentration with a surface tension minimum at concentration c(min). The increase of surface tension above c(min) may be related to the formation of clusters consisting of NaHA chain and dimeric surfactants at the air-water interface and in the bulk. From light scattering measurements, molecular weight, hydrodynamic radius, and second virial coefficient have been calculated. The simple calculation of the ratio of positive charge of dimeric surfactant unit per one negatively charged hyaluronate disaccharidic unit in NaHA-surfactant complex reveals that there is a slight excess of positive surfactant charges per one negatively charged disaccharidic unit in the region around c(min) and the NaHA-surfactant complex is not far from electroneutrality. The nonlinear behavior of viscosity vs surfactant concentration in the NaHA-dimeric surfactant system depends on surfactant chemical structure. The behavior is concerned with the size increase due to complex growth and with the size shrinkage above c(min). A model describing the behavior of NaHA-surfactant complex in the bulk and at the interface is suggested. Copyright 2000 Academic Press.

Journal Article↗
PubMed1999

[Inter-organ variability in enzymatic hydrolysis of ammonium salts in rats in vitro].

The study evaluated the rate and kinetics of enzymatic hydrolysis of N-(2-benzoyloxyethyl)-alkyl-dimethylammonium bromides, potential easily biodegradable disinfectants of soft character. The products of enzymatic hydrolysis of the substrates under study, catalysed by microsomal esterase, included substituted substrates choline and benzoic acid which, as a hydrolytic product, was essayed by HPLC. The effect of the length of the alkyl chain of the individual homologues on the rate of enzymatic hydrolysis and their affinity to microsomal esterase of the rat liver and lung in vitro was examined. The structural modification (varying length of the aliphatic chain on the ammonium nitrogen of these compounds) was found to significantly influence the kinetics of enzymatic hydrolysis of the esteric bond. From the viewpoint of the rate of enzymatic hydrolysis no significant inter-organ variability was observed: in the liver as well as the lung the dependence of the rate of enzymatic hydrolysis on the length of the aliphatic chain possesses the shape of a falling hyperbole with the maxima for BCH2 > BCH4 > BCH8 = BCH10. The specific activity of both esterases ranges within 0.2-3.5 nmol.min-1.mg-1. From the viewpoint of affinity, a marked inter-organ difference was manifested by 10 times higher affinity of the substrates to the lung microsomal esterase in comparison with the liver one. The effect of the length of the alkyl of the individual homologues on the affinity is of a non-linear character also in this case. In both organs, a certain correlation was found between the rate of enzymatic hydrolysis and affinity to microsomal esterases.

Animals↗
PubMed1997

Effect of N-lauryl-N,N-dimethylamine N-oxide on dimyristoyl phosphatidylcholine bilayer thickness: a small-angle neutron scattering study.

Small-angle neutron scattering on large extruded unilamellar dimyristoyl phosphatidylcholine (DMPC) liposomes was used to determine the DMPC bilayer thickness dL and its change in the presence of N-lauryl-N,N-dimethylamine N-oxide (LDAO). At 36 degrees C, the values of dL are dL = 3.44 +/- 0.10 nm and dL = 2.90 +/- 0.10 nm in pure DMPC bilayers and in bilayers at DMPC:LDAO = 2:1 molar ratio, respectively. Using the specific volumes of DMPC and LDAO and supposing that the molecular volumes and surface areas in the bilayer are additive, the surface areas of DMPC (ADMPC) and of LDAO (ALDAO) were found to be at 36 degrees C: ADMPC = 0.644 +/- 0.018 nm2 and ALDAO = 0.25 +/- 0.05 nm2.

Dimethylamines↗
PubMed1996

Cut-off effects in biological activities of surfactants.

In the homologous series of long hydrocarbon chain surface active compounds, their various biological activities increase progressively with increasing chain length up to a critical point, beyond which the compounds cease to be active. The paper reviews several hypotheses of this cut-off effect in biological activities and experimental evidences supporting them. It is suggested that the lateral expansion of the phospholipid bilayer of biological membranes caused by the intercalation of long-chain amphiphile molecules between the phospholipid molecules and the mismatch between their hydrocarbon chain lengths results in the creation of free volume in the bilayer hydrophobic region. The elimination of the free volume via the hydrocarbon chain trans-gauche isomerisation or interdigitation results in the bilayer thickness change or in its destabilisation and formation of non-bilayer phase(s). In combination with the partition and ionisation equilibria of amphiphiles in the lipid/aqueous phase systems, the free volume predicts similar chain length and pH dependencies as observed in biological experiments. It is suggested that the free volume mechanism, in combination with other mechanisms, could be responsible for the cut-off effects in biological activities of amphiphiles.

Cell Membrane↗
PubMed1996

QSAR and CAMM study of amphiphilic antimicrobially active 2,2'-bipyridyl monoammonium salts.

Preparation of 2,2'-bipyridyl monoammonium salts is described as well as their conformation study using computer aided molecular modelling (CAMM) methods and quantitative relations between structure, aggregation properties and antimicrobial activity (QSAR) of these derivatives. It was found that using the applied synthetic route the monoammonium salt is prepared free of bis-ammonium salt. While in the case of the unsubstituted 2,2'-bipyridyl the energy difference between s-cis and s-trans conformers is minor and the transition from one state into the other one is possible with s-trans state apparently being preferred, after quaternisation the exclusive conformer is s-cis that is in this state fixed except of steric hindrance between the alkyl substituent bonded to the N+ atom and the hydrogen bonded to 3'C also by a weak hydrogen interaction C-H ... N between the hydrogen of the first carbon of the alkyl chain and the nitrogen of the adjacent ring. This finding is supported also by the results of calculation of point electric charges, dipole moments, 2C-2'C distance and torsion angles of non-quaternised as well as bipyridinium cations. It follows from quantitative dependencies between lipophilicity (expressed by means of aggregation properties-by critical concentration of micelle formation ck, and chromatographic factor RM), structure (length of alkyl chain m) and antimicrobial activity (minimum inhibition concentration, MIC) that the maximum of activity is achieved with compounds of chain length m = 13 to 16 with ck about 1.10(-3) mol/l. It follows from the comparison with simple alkylpyridinium salts that the mechanism of biological activity at the bacterial level will not differ in 2,2'-dipyridyl derivatives from the mechanism of activity of other ammonium salts.

2,2'-Dipyridyl↗
PubMed1995

Suppression of virulence factors of pseudomonas aeruginosa by subinhibitory concentrations of quaternary ammonium salts.

The effect of subinhibitory concentrations (sub-MICs) of two homologous series of "soft" quaternary ammonium salts (QATs) upon the expression of phospholipase C (Pseudomonas aeruginosa strain 72/92), elastase, proteinase and permeability activity (P. aeruginosa 9/92) was studied. Both strains were isolated from the patients suffering from nosocomial infections. Phospholipase C was the most markedly inhibited enzyme. The inhibitory effect was directly proportional to the concentration of substances but the degree of inhibition in the two homologous series was different. In the second strain of P. aeruginosa its production of elastase, permeability factor and mainly its proteinase activity were less affected by the series of tested QATs. A significant inhibition of production of these factors was manifested only in higher concentrations particularly by the substances with longer alkyls. The effect of QATs on the production of virulence factors could be attributed to their influence on the metabolic activity of organisms.

Animals↗
PubMed1994

Quantitative relationships between structure and antimicrobial activity of new "soft" bisquaternary ammonium salts.

New surface-active bisquaternary ammonium salts derived from bis-(2-dimethylaminoethyl) ester of glutaric acid are highly effective against representatives of Gram-positive, Gram-negative bacteria and yeasts. Relationships between structure, lipophilicity and antimicrobial effectiveness were demonstrated by quantitative structure-activity methodology. The non-linear dependence of biological activity on the structure as well as lipophilicity (expressed as critical micelle concentration-CMC) was shown using Kubinyi's bilinear model. The most effective compounds were those with the alkyl chain of 11-12 carbon atoms and with the CMC values around 0.7-1.0 mmol/L. These derivatives possessed higher antimicrobial activity particularly to Gram-negative bacteria.

Anti-Bacterial Agents↗
PubMed1994

Effects of 4-alkylmorpholine N-oxides on ATP-producing processes in Ehrlich ascites and L1210 leukaemia cells.

The main purpose of the present investigation was to study the effect of the homologous series of 4-alkylmorpholine N-oxides on ATP-producing processes in Ehrlich ascites and L1210 murine leukaemia cells. The effects on aerobic glucose consumption, lactic acid formation, content of total (T-SH) and non-protein thiol groups (NP-SH), endogenous and exogenous respiration and the level of ATP in tumour cells incubated in vitro were investigated. 4-Dodecylmorpholine N-oxide (DMNO), one of the most active compounds, decreased the level of ATP immediately after addition to the suspension of Ehrlich cells in an ice bath. After 2 h incubation at 37 degrees C the drop in the ATP level was much lower. A possible explanation for the decrease in the ATP level might be interaction of the amine oxide with the cell membrane.

Adenosine Triphosphate↗
PubMed1993

Elimination of plasmid pKM101 from Salmonella typhimurium by monoammonium salts.

The frequency of elimination of plasmid pKM101 from Salmonella typhimurium TA92 exposed to the action of 1-alkyl-1-ethylpiperidinium bromides and N-alkyl-N-[5-(benzoyloxy)-3-oxapentyl]-N,N-dimethylammonium bromides was non-linear in the homologous series. Change in the length of the alkyl chain markedly affected the elimination properties of the piperidine derivatives but had no effect on the elimination of benzoyl derivatives. Piperidines exhibited a weaker elimination capacity than the benzoyl derivatives. The most potent eliminator was the octylbenzoyl derivative, which causes the elimination of the plasmid in 80-85% cells.

Bromides↗