Organometallics and quaternary ammonium salts affect calcium ion desorption from lecithin liposome membranes.

The objective of the present work was to compare the effects of groups of tin and lead organometallic compounds and their mixtures with amphiphilic quaternary ammonium salts (QAS) on the process of calcium ion desorption from lecithin liposome membranes, as dependent on the properties of the hydrophilic and hydrophobic parts of QAS. In the investigations the method of radioactive labels was applied. Synergism and antagonism in the action of both groups of compounds were found. The effectiveness of the cooperation depended more on chain length of QAS compounds than on the size and polarity of their hydrophobic parts. The most effective of all compounds studied was a the mixture of benzyldimethylammonium chloride in a mixture with tripropyltin. Since the rate of calcium desorption proved to be a good measure of efficacy of biologically active surfactants, it seems that the conclusions reached in this paper may be useful for choosing compounds which are able to decontaminate the environment polluted with heavy metals.

Influence of amphiphilic compounds on membranes.

On the basis of Gortel & Grendel (J. Exp. Med., 1925, 41, 439-494) discovery, the importance of the lipid bilayer as an integral and indispensible component of the cell membrane is discussed. In particular, attention focuses on the interaction between membranes and amphiphilic substances. The effect on membranes of quaternary ammonium salts, both in the form of pesticides and oxidants as well as organic compounds of tin and lead are discussed in greater detail.

Influence of some lysosomotropic compounds on calcium ion desorption process from liposome membrane.

The effect of a group of model lysosomotropic compounds on the process of Ca2+ ion desorption from lecithin liposome membranes was studied. The compounds studied were: hydrochlorides of fatty acids 2-dimethylaminoethyl esters (DM-n) for n = 9, 11, 13 and 15 carbon atoms in the fatty acid alkyl chain and methochloride of 2-dimethylaminoethyl laurate (DMS-11). It was found that all the compounds studied caused increased desorption with increasing concentration of the compound. Most effective was the quaternary ammonium salt, DMS-11. Moreover, it was found that the process of Ca2+ desorption from the membrane depended on pH of the medium. Compound DM-11 was more active at pH 8 than at pH 5. The action of DM-n compounds depended on the alkyl chain length, DM-11 and DM-13 being the most active. Apparently free amines penetrate the phospholipid membranes and incorporate into its hydrophobic core causing structural deformations. Hydrochlorides of fatty acids and the quaternary ammonium salt induce desorption of calcium ions mostly as a result of competitive electrostatic interactions. By quantum chemistry, PM3 method, and methods of molecular modelling we established the higher hydrophilicity of the polar head of DM-n series with respect to the polar head of the DMS-n compounds. DM-n compounds possess both acceptor and donor properties for hydrogen bonding while DMS-n are instrumental as acceptors only. It should be noted, that the results obtained in this paper for model membranes are in accordance with those for biological ones.

All-atom empirical potential for molecular modeling and dynamics studies of proteins.

New protein parameters are reported for the all-atom empirical energy function in the CHARMM program. The parameter evaluation was based on a self-consistent approach designed to achieve a balance between the internal (bonding) and interaction (nonbonding) terms of the force field and among the solvent-solvent, solvent-solute, and solute-solute interactions. Optimization of the internal parameters used experimental gas-phase geometries, vibrational spectra, and torsional energy surfaces supplemented with ab initio results. The peptide backbone bonding parameters were optimized with respect to data for N-methylacetamide and the alanine dipeptide. The interaction parameters, particularly the atomic charges, were determined by fitting ab initio interaction energies and geometries of complexes between water and model compounds that represented the backbone and the various side chains. In addition, dipole moments, experimental heats and free energies of vaporization, solvation and sublimation, molecular volumes, and crystal pressures and structures were used in the optimization. The resulting protein parameters were tested by applying them to noncyclic tripeptide crystals, cyclic peptide crystals, and the proteins crambin, bovine pancreatic trypsin inhibitor, and carbonmonoxy myoglobin in vacuo and in crystals. A detailed analysis of the relationship between the alanine dipeptide potential energy surface and calculated protein φ, χ angles was made and used in optimizing the peptide group torsional parameters. The results demonstrate that use of ab initio structural and energetic data by themselves are not sufficient to obtain an adequate backbone representation for peptides and proteins in solution and in crystals. Extensive comparisons between molecular dynamics simulations and experimental data for polypeptides and proteins were performed for both structural and dynamic properties. Energy minimization and dynamics simulations for crystals demonstrate that the latter are needed to obtain meaningful comparisons with experimental crystal structures. The presented parameters, in combination with the previously published CHARMM all-atom parameters for nucleic acids and lipids, provide a consistent set for condensed-phase simulations of a wide variety of molecules of biological interest.

Interaction between model membranes and a new class of surfactants with antioxidant function.

The effect of two series of amphiphilic quaternary ammonium salts on some properties of phospholipid membranes was studied. The compounds of one series, N-benzyl-N,N-dimethyl-N-alkyl ammonium bromides, exert a destructive effect on membranes and are treated as reference compounds. The compounds of the other series, N-(3,5-di-t-butyl-4-hydroxy)benzyl-N,N-dimethyl-N-alkyl ammonium bromides, are derivatives of the former ones, exhibit antioxidant properties, and do only relatively slight damage to the membranes. The aim of the work was to explain the difference in molecular interaction with membranes between the two kinds of hydrophobic compounds. Thermodynamic methods, a new mixing technique, and monolayer and quantum calculation methods were used. It has been shown that the antioxidant molecules are less hydrophobic than those of the reference compounds and disturb the membrane organization to a lesser extent. On the basis of monolayer data, we suggest that the studied antioxidant behaves like a substitutional impurity, whereas the reference behaves like an interstitial one.

Combined extracts of Urtica dioica and Pygeum africanum in the treatment of benign prostatic hyperplasia: double-blind comparison of two doses.

The 134 patients (aged 53 to 84 years) with symptoms of benign prostatic hyperplasia were drawn from two medical centers in Warsaw. The patients were randomly assigned to receive two capsules of the standard dose of an urtica/pygeum preparation (300 mg of Urtica dioica root extract combined with 25 mg of Pygeum africanum bark extract) or two capsules containing half the standard dose twice daily for 8 weeks. After 28 days' treatment, urine flow, residual urine, and nycturia were significantly reduced in both treatment groups. After 56 days' treatment, further significant decreases were found in residual urine (half-dose group) and in nycturia (both groups). There were no between-group differences in these measures of efficacy. Five patients reported adverse effects of treatment; treatment was not discontinued in any patient because of side effects. It is concluded that half doses of the urtica/pygeum extract are as safe and effective as the recommended full doses.

Voltage-dependent behaviour of dolichyl phosphate-phosphatidylcholine bilayer lipid membranes.

The current-voltage steady-state characteristics, cyclic voltammograms and capacitance-voltage steady-state relationships of bilayer lipid membranes made from dioleoylphosphatidylcholine or its mixtures with dolichyl-12 phosphate have been studied. Sustained fluctuations of the capacitance of dolichyl phosphate modified bilayers under applied voltage were observed. The results suggest that the dynamics of dolichyl phosphate molecules in membranes can be regulated by transmembrane electrical potential.

Amphiphilic derivatives of betaine esters as modifiers of macrovesicular BLM.

A series of amphiphilic derivatives of betaine esters (V-n), with the chemical structure (CH3)3N+COOCnH2n + 1Cl- (n = 10, 12, 14 or 16) were studied with respect to their effects on the electrical properties of lecithin macrovesicular membranes. Normalized resistance and breakdown voltage were found to depend on the V-n concentration in the membrane and on the alkyl chain length (n). Resistance decreases up to about 10(4) ohm.cm2 and breakdown voltage decreases by 111 mV were detected in the V-n: lecithin molar ratio range measured (0.005-0.05). Maximal decrease in breakdown voltage was observed for V-14. These findings together with the featured anionic selectivity suggest that, due to the interaction of V-n with phospholipids, hydrophilic pores are formed in the lipid bilayers. This assumption is supported by the results obtained by electron paramagnetic resonance (EPR) measurements which showed no collective changes in bilayer dynamics or ordering. In particular, rotational correlation times and order parameters of the spin probe molecules dissolved in the membrane did not change in the concentration range tested. Since a large number of defects in the membrane can be expected to influence the collective ordering and dynamics, this observation also suggest that the number of pores formed is small.

Effects of some cyclic elements containing amphiphilic compounds on stability and transport properties of model lecithin membranes.

The paper presents results of studies on changes in model membrane properties induced by some single-chain amphiphilic quaternary ammonium salts with fungicidal activity, N-dodecyl-N-methylmorpholinium chloride (IVC), N-dodecyloxymethylene-N-methylmorpholinium chloride (IVD), N-dodecyl-N-methylpiperidinium chloride (VIC), N-dodecyloxymethylene-N-methylpiperidinium chloride (VID) and N-dodecyl-N,N-dimethyl-N-benzy-lammonium chloride (IB). Two different lipid systems were used, namely, unilamellar liposomes and black planar membranes (BLM). All the compounds studied interfered with sulphate ion transport across liposomal membranes as well as with calcium ion desorption from the membranes. The compounds were found also to change the stability of black lecithin membranes. Generally the sequence of effectiveness of the salts studied on both models used was: IB greater than VID greater than IVD greater than VIC greater than IVC, although there were some differences for particular processes. The results obtained are discussed in view of a possible mechanism of the interaction between the salts studied and the lipid model including the role the salt head group structure and charge distribution can play in this interaction.

Properties of lecithin-dodecaprenol macrovesicular bilayer membranes.

The ionic transport properties, capacitance and breakdown voltage of bilayer macrovesicles made from lecithin, dodecaprenol and their mixtures have been studied. The electrical measurements showed that polyprenol in lipid bilayers increases membrane permeability and elasticity, and decreases membrane thickness. Some physiological implications of these findings are indicated.

The influence of uremic sera on the blastic transformation of lymphocytes of healthy subjects, stimulated with non-specific mitogens (PHA, con A, PWM).

The influence of uremic sera on the blastic response of lymphocyte of healthy subjects to nonspecific mitogens (PHA, Con A, PWM) in 3-day culture was investigated. Sera were obtained from 19 patients with renal insufficiency, among them 3 groups were distinguished: terminal renal insufficiency and acute renal insufficiency, both treated by hemodialysis, and severe chronic renal insufficiency treated conservatively. Generally, the statistically significant inhibitory influence of uremic sera on the blastic transformation values of lymphocytes of healthy subjects stimulated with nonspecific mitogens was found. There were no significant changes in inhibitory activity of sera obtained before and after hemodialysis. Inhibitory properties of uremic sera were similar in regard to blastic transformations stimulated with all mitogens used. The studies on the influence of the experimental stationary dialysis in vitro on the inhibition of blastic transformation by the uremic sera showed that under the specific conditions of diffusion, blastic transformation inhibitors passed through dialysis membrane and were removed from the sera. Among all tested sera there were only 2 which did not lower the blastic transformation values. The fact that they were obtained from the chronically dialyzed patients with the longest period of dialysotherapy supported the above observation.

Subpopulations of T and B lymphocytes in peripheral blood and lymphocytes reactivity to non-specific mitogens (PHA, Con A, PWM) in in vitro cultures in patients suffering from in vitro cultures in patients suffering from glomerulonephritis.

Studies were performed on 79 subjects, out of which 32 belonged to the control group and 47 suffered from glomerulonephritis. The number of T and B lymphocytes in peripheral blood was determined using the technique of E, EA and EAC-rosette tests. Also, the lymphocyte blast response to non-specific mitogens (PHA, Con A, PWM) was established in vitro. Patients suffering from acute proliferative glomerulonephritis, as compared to the control group, displayed a statistically significant increase of lymphocytes with the receptor for complement (EAC-rosettes). Their reactivity to all three mitogens did not differ from the values obtained in the control group. In patients suffering from chronic glomerulonephritis (proliferative, membranous-proliferative, membranous), shiftings in the contents of the peripheral blood lymphocytes pools were of opposite directions, i.e., statistically significant in comparison with the control group. Also an increase in the absolute number of T lymphocytes (E-rosettes) was observed. Generally speaking, the values of blast transformations after mitogen stimulations were smaller in patients suffering from chronic than in those suffering from acute glomerulonephritis. In 1/3 of them, the decrease of blast response to one of the three mitogens was detected. The decrease exceeded the lower limit of values of healthy subjects, and most often, it was connected with Con A stimulation.