Mean Charge Density Research Articles

Electric double layers with modulated surface charge density: exact 2D results

Electric double layers (EDL) with counterions only, say electrons with the elementary charge −e, in thermal equilibrium at the inverse temperature β are considered. In particular, we study the effect of the surface charge modulation on the particle number density profile and the pressure. The mobile particles are constrained to the surface of a 2D cylinder and immersed in vacuum (no dielectric image charges). An EDL corresponds to the end-circle of the cylinder which carries a (fixed) position-dependent line charge density. The geometries of one single EDL and two EDLs at distance d are considered; the particle density profile is studied for both geometries, the effective interaction of two EDLs is given by the particle pressure on either of the line walls. For any coupling constant Γ ≡ βe 2 = 2 × integer, there exists a mapping of the 2D one-component Coulomb system onto the 1D interacting anticommuting-field theory defined on a chain of sites. Using specific transformation symmetries of anticommuting variables, the contact value theorem is generalized to the EDL with modulated line charge density. For the free-fermion coupling Γ = 2 it is shown that, under certain conditions, the matrix of interaction strengths between anticommuting variables diagonalizes itself which permits one to obtain exact formulas for the particle density profile as well as the pressure. The obtained results confirm the previous indications of weak-coupling and Monte Carlo observations that the surface charge inhomogeneity implies an enhancement of the counterion density at the contact with the charged line and a diminution of the pressure between two parallel lines in comparison with the uniformly charged ones (with the same mean charge densities).

Effect of Cooling Medium on LDPE Dielectric Properties.

Polyethylene, with its excellent mechanical and dielectric properties is used as an insulator for high-voltage direct current (HVDC) transmission. In ultra-high-voltage direct current (UHVDC) transmission, the ageing of insulation materials caused by space charge under high DC voltage becomes serious. Therefore, restraining the space charge and improving the dielectric properties of HVDC cables is important. In this study, low-density polyethylene (LDPE) was used as the raw material and combined with cooling media in a vulcanizing press. A polarizing microscope was used to observe the samples’ crystal morphologies. The space charge accumulation and dispersion were detected using pulsed electro-acoustic. Additionally, dielectric properties such as electrical conductivity and dielectric frequency spectrum were tested. The grain size in the air-cooled LDPE samples was found to be large and unevenly dispersed. However, the grain sizes in the water and oil cooling LDPE samples were small. The mean charge density of the oil cooling samples was the lowest. Under a short circuit measurement, more space charges were found in the natural and rapid air cooling samples. The mean charge densities of these two samples were high, with a fast decay rate. With an 8 and 50 kV/mm electric field strength, the oil cooling samples’ conductivity was the highest and lowest, respectively.

On the Gouy–Chapman–Stern model of the electrical double-layer structure with a generalized Boltzmann factor

The classical treatment of the electrical double-layer (EDL) structure at a planar metal/electrolyte junction via the Gouy–Chapman–Stern (GCS) approach is based on the Poisson equation relating the electrostatic potential to the net mean charge density. The ions concentration in the diffuse layer are assumed to follow the Boltzmann distribution law, i.e. ∝exp(−ψ̃) where ψ̃ is the dimensionless electrostatic potential. However, even in stationary equilibrium in which variables are averaged over a large number of elementary stochastic events, deviations from the mean-value are expected. In this study we evaluate the behavior of the EDL by assuming some small perturbations superposed on top of its Boltzmann distribution of ion concentrations using the Tsallis nonextensive statistics framework. With this we assume the ion concentrations to be proportional to [1−(1−q)ψ̃]1/(1−q)=expq(−ψ̃) with q being a real parameter that characterizes the system’s statistics. We derive analytical expression and provide computational results for the overall differential capacitance of the EDL structure, which, depending on the values of the parameter q can show both the traditional inverse bell-shaped curves for aqueous solutions and bell curves observed with ionic liquids.

Moving away from singly-magic nuclei with Gorkov Green’s function theory

Ab initio calculations of bulk nuclear properties (ground-state energies, root mean square charge radii and charge density distributions) are presented for seven complete isotopic chains around calcium, from argon to chromium. Calculations are performed within the Gorkov self-consistent Green's function approach at second order and make use of two state-of-the-art two- plus three-nucleon Hamiltonians, $NN$+$3N\text{(lnl)}$ and NNLO$_{\text{sat}}$. An overall good agreement with available experimental data is found, in particular for differential energies (charge radii) when the former (latter) interaction is employed. Remarkably, neutron magic numbers $N=28,32,34$ emerge and evolve following experimental trends. In contrast, pairing gaps are systematically underestimated. General features of the isotopic dependence of charge radii are also reproduced, as well as charge density distributions. A deterioration of the theoretical description is observed for certain nuclei and ascribed to the inefficient account of (static) quadrupole correlation in the present many-body truncation scheme. In order to resolve these limitations, we advocate the extension of the formalism towards incorporating breaking of rotational symmetry or, alternatively, performing a stochastic sampling of the self-energy.

Sounding observation of vertical electric field in eyewall of Typhoon Wipha (No. 1907) during landing period

In the summer of 2019, one case of electric field sounding in eyewall of No.1907 typhoon named Wipha was obtained in Wenchang, Hainan Island, China. Up to now, it has been the first case of electric field sounding results obtained in a typhoon system. In this paper, based on the observations of satellite, meteorological radar, ground electric field and cloud-to-ground flash location data of Hainan province, China, the basic characteristics of the typhoon are analyzed in detail. Owing to the limitation of cloud-to-ground flash location system, only flash activities of the typhoon before and after landing period are analyzed and the result does not show obvious features as reported by other researches. Referring to the radar reflectivity and sounding path, we confirm that the sounding penetrates through the eyewall region of the typhoon from cloud base to top. The electric field profile and the charge region distribution in the sounding path area are analyzed, and the results show that four positive and three negative charge regions exist between 5.74 and 9.10 km above sea level and the corresponding temperatures range from –2.4 to –16.7 ℃ of the seven charge regions. The mean charge densities of each charge region from bottom to top are 0.63 nC/m<sup>3</sup>, –0.33 nC/m<sup>3</sup>, 0.31 nC/m<sup>3</sup>, –1.03 nC/m<sup>3</sup>, 1.70 nC/m<sup>3</sup>, 1.57 nC/m<sup>3</sup> and –1.20 nC/m<sup>3</sup>, respectively. According to the preliminary analysis, we consider that the two positive charge layers at the top should be in the same charge region. Under the comprehensive consideration of the thickness of charge regions, the intensities of these six charge regions are 0.33 nC/m<sup>2</sup>, –0.07 nC/m<sup>2</sup>, 0.06 nC/m<sup>2</sup>, –0.87 nC/m<sup>2</sup>, 0.73 nC/m<sup>2</sup>, and –0.18 nC/m<sup>2</sup>, respectively. We can find that there are three dominant charge regions with largest intensity and they are the lowest positive charge region, the middle main negative region, and upper main positive charge region. And these vertical distributions of the three dominant charge regions are characterized by a tripole charge structure. These results are basically consistent with some simulation results. In addition, a negative screen charge region with a shallow depth in a range of 15–20 dBZ of the upper cloud boundary can be found. Combining the popular charging mechanisms, the similarity of tripole charge structure between our sounding and normal thunderstorm are discussed, and we preliminary consider that the non-inductive charging mechanism and the inductive charging mechanism, which originate from normal convection, are also suitable for eyewall region of typhoon.

Charge Calibration Standard for Atomic Force Microscope Tips in Liquids.

An electric charge standard with nanoscale resolution is created using the known charge distribution of a single tobacco mosaic virus coat protein combined with the known packing of these proteins in the virus capsid. This advances the ability to measure charge on nanometric samples. Experimental atomic force microscope (AFM) force-distance curves are collected under aqueous conditions with controlled pH and ion concentration. A mathematical model that considers a polarizable dielectric tip immersed in an electrolyte is used to obtain charge density from the AFM measurements. Interactions between the tip and the sample are modeled using theory that includes monopolar electrostatic interactions, dipolar interactions, screening from both the dielectric nature of ambient water and solvated ions as described by the linear Poisson-Boltzmann equation, and hard-core repulsion. It is found that the tip charge density changes on a timescale of hours requiring recalibration of the tip for experiments lasting more than an hour. As an example of how a charge-calibrated tip may be used, the surface charge densities on 20 individual carboxylate-modified polystyrene (PS) beads are measured. The average of these AFM-measured bead charge densities is compared with the value obtained from conventional titration combined with electron microscopy. The two values are found to agree within 20%. While the comparison demonstrates similarity of the two charge measurements, hypotheses are put forward as to why the two techniques might be expected not to provide identical mean charge densities. The considerations used to build these hypotheses thus underscore the relevance of the method performed here if charge information is required on individual nanoparticles.

Transcription Factor Binding Affinities and DNA Shape Readout.

SummaryAn essential event in gene regulation is the binding of a transcription factor (TF) to its target DNA. Models considering the interactions between the TF and the DNA geometry proved to be successful approaches to describe this binding event, while conserving data interpretability. However, a direct characterization of the DNA shape contribution to binding is still missing due to the lack of accurate and large-scale binding affinity data. Here, we use a binding assay we recently established to measure with high sensitivity the binding specificities of 13 Drosophila TFs, including dinucleotide dependencies to capture non-independent amino acid-base interactions. Correlating the binding affinities with all DNA shape features, we find that shape readout is widely used by these factors. A shape readout/TF-DNA complex structure analysis validates our approach while providing biological insights such as positively charged or highly polar amino acids often contact nucleotides that exhibit strong shape readout.

Influence of temperature and electric field strength on the space charge behavior of liquid silicone rubber with carbon black nanofillers

In order to explore the space charge behavior of liquid silicone rubber (LSR) the pulsed electroacoustic (PEA) method has been applied. Due to the elastic nature of LSR, the PEA setup was optimized to ensure a constant contact pressure and thus a constant thickness of the LSR samples. For each sample, the temperature of the ground and the high-voltage electrode was permanently measured. The space charge behavior was investigated for neat LSR and for LSR samples with two different amounts of nanoscaled carbon black (CB). The results show in general a formation of homocharges at both electrodes. At 20 °C, the negative charge from the cathode moves towards the anode in the case of neat LSR. With increasing amount of CB, the negative charge is trapped near the cathode and the charge migration is suppressed. At higher temperature, an increasing amount of positive homocharges at the anode is observed, which is suppressed for LSR with CB nanofillers. The mean charge density between the electrodes is evaluated during polarization and depolarization measurement. The results show that the mean charge density increases with temperature and electric field strength, which is explained by the Schottky and Poole-Frenkel effect. In addition, it is observed that the mean attenuation rate during the depolarization time increases with increasing amount of CB nanofillers.

Measurements of vertical electric field in a thunderstorm in a Chinese inland plateau

Abstract. A balloon-borne instrument was designed to measure the electric field in thunderstorms. One case of thunderstorm was observed in the Pingliang region (35.57∘ N, 106.59∘ E; and 1620 m above sea level, a.s.l.) of a Chinese inland plateau, through penetration by the balloon-borne sounding in the early period of the mature stage. Results showed that the sounding passed through seven predominant charge regions. A negative charge region with a depth of 800 m located near the surface, and a positive charge region appeared in the warm cloud region; their mean charge densities were −0.44 ± 0.136 and 0.43 ± 0.103 nC m−3, respectively. Five charge regions existed in the region colder than 0 ∘C, and charge polarity alternated in a vertical direction with a positive charge at the lowest region. The mean charge densities for these five regions were 0.40±0.037 nC m−3 (−9.5 to −4 ∘C), -0.63±0.0107 nC m−3 (−18 to −14 ∘C), 0.35±0.063 nC m−3 (−27 to −18 ∘C), -0.36±0.057 nC m−3 (−34 to −27 ∘C), and 0.24±0.06 nC m−3 (−38 to −34 ∘C). We speculated that the two independent positive charge regions in the lower portion are the same charge region with a weak charge density layer in the middle. The analysis showed that the real charge structure of the thunderstorm is more complex than the tripole model, and the lower dipole is the most intensive charge region in the thunderstorm. Keywords. Meteorology and atmospheric dynamics (atmospheric electricity)

Management of Deep Brain Stimulator Battery Failure: Battery Estimators, Charge Density, and Importance of Clinical Symptoms

ObjectiveWe aimed in this investigation to study deep brain stimulation (DBS) battery drain with special attention directed toward patient symptoms prior to and following battery replacement.BackgroundPreviously our group developed web-based calculators and smart phone applications to estimate DBS battery life (http://mdc.mbi.ufl.edu/surgery/dbs-battery-estimator).MethodsA cohort of 320 patients undergoing DBS battery replacement from 2002–2012 were included in an IRB approved study. Statistical analysis was performed using SPSS 20.0 (IBM, Armonk, NY).ResultsThe mean charge density for treatment of Parkinson’s disease was 7.2 µC/cm2/phase (SD = 3.82), for dystonia was 17.5 µC/cm2/phase (SD = 8.53), for essential tremor was 8.3 µC/cm2/phase (SD = 4.85), and for OCD was 18.0 µC/cm2/phase (SD = 4.35). There was a significant relationship between charge density and battery life (r = −.59, p<.001), as well as total power and battery life (r = −.64, p<.001). The UF estimator (r = .67, p<.001) and the Medtronic helpline (r = .74, p<.001) predictions of battery life were significantly positively associated with actual battery life. Battery status indicators on Soletra and Kinetra were poor predictors of battery life. In 38 cases, the symptoms improved following a battery change, suggesting that the neurostimulator was likely responsible for symptom worsening. For these cases, both the UF estimator and the Medtronic helpline were significantly correlated with battery life (r = .65 and r = .70, respectively, both p<.001).ConclusionsBattery estimations, charge density, total power and clinical symptoms were important factors. The observation of clinical worsening that was rescued following neurostimulator replacement reinforces the notion that changes in clinical symptoms can be associated with battery drain.

Effects of electrostatic correlations on electrokinetic phenomena

The classical theory of electrokinetic phenomena is based on the mean-field approximation that the electric field acting on an individual ion is self-consistently determined by the local mean charge density. This paper considers situations, such as concentrated electrolytes, multivalent electrolytes, or solvent-free ionic liquids, where the mean-field approximation breaks down. A fourth-order modified Poisson equation is developed that captures the essential features in a simple continuum framework. The model is derived as a gradient approximation for nonlocal electrostatics of interacting effective charges, where the permittivity becomes a differential operator, scaled by a correlation length. The theory is able to capture subtle aspects of molecular simulations and allows for simple calculations of electrokinetic flows in correlated ionic fluids. Charge-density oscillations tend to reduce electro-osmotic flow and streaming current, and overscreening of surface charge can lead to flow reversal. These effects also help to explain the suppression of induced-charge electrokinetic phenomena at high salt concentrations.

The mechanism of photoinduced electron transfer in the d-amino acid oxidase–benzoate complex from pig kidney: Electron transfer in the inverted region

Abstract d -Amino acid oxidase (DAAO) from pig kidney binds flavin adenine dinucleotide (FAD) as a cofactor. The DAAO–benzoate (Bz) complex (DAOB) is remarkably more stable than DAAO. It was previously reported that the fluorescence lifetime of FAD in DAAO is reduced by 66% upon Bz binding. The mechanism of photoinduced electron transfer (ET) in the DAOB monomer from Bz to the excited isoalloxazine (Iso*) was studied by molecular dynamics simulation (MDS) and by Kakitani and Mataga electron transfer theory (KM theory), and compared with that in DAAO. The ET parameters contained in KM theory were determined to obtain the fluorescence lifetime of DAOB (60 ps). The ET mechanism in DAOB is different from other flavoproteins, where neutral tryptophans and tyrosines are the ET donors, since the anionic Bz acts as the anionic ET donor in DAOB. Moreover, ET takes place in the inverted region. Charge transfer interaction (CT) was studied by semi-empirical molecular orbital (MO) methods. The dipole moment in the Iso*–Bz system was lower than that in the isoalloxazine (Iso)–Bz system, which was ascribed to CT from the negatively charged Bz to Iso*. The mean interaction energies between Iso and Bz over 100 snapshots were −16.8 and −8.1 kcal/mol in the excited and the ground states, respectively, with mean charge densities for the excited and the ground states of −0.354 and −0.013 at Iso and −0.646 and −0.987 at Bz, respectively. The ionization potential of Bz was evaluated as 7.3 eV by ET analysis, which was in excellent agreement with that obtained by MO calculations. The dielectric constant between Iso and the donors was 2.2 in DAOB, compared to 5.8 in DAAO. According to the MDS, several water molecules existed around Iso in DAAO that were all removed upon Bz binding resulting in a strongly non-polar environment near Iso in DAOB.

Application of the topological analysis of the electronic localization function to archetypical [Pb(II)Ln]p complexes: The bonding of Pb2+ revisited

The coordination of neutral ligands (L = OC, HCN, NH3, PH3, SH2, HNCO and H2O) to Pb2+ is investigated and analyzed by means of the topological analysis of the Electronic Localization Function (ELF). It is shown that the mean charge density of the V(Pb) basin (<rho>(V(Pb))) can reach a ligand-independent limiting value from n = 6, a coordination number from which the [PbL(n)]2+ complexes adopt holodirected structures. The investigations performed on anionic series (L = HS-, OH-, CN-, F-, Cl-, and Br-) lead to optimized stable structures in which the coordination number does not exceed n = 4, even in the presence of a model aqueous solvent. This different behavior with respect to the neutral ligand series is interpreted by means of natural populations and electrostatic repulsions. The main result of this contribution is that stable Pb(II) complexes could be those exhibiting reasonable values of <rho>(V(Pb)), namely those not exceeding the saturation plateau evidenced in the present piece of work.

Structural characterization and antithrombin activity of dermatan sulfate purified from marine clam Scapharca inaequivalvis

Glycosaminoglycans from the body of marine clam Scapharca inaequivalvis were extracted at about 0.15- 0.18 mg/g of dry tissue, composed of dermatan sulfate (DS) (approx. 74%) and heparan sulfate (26%). After treatment with nitrous acid, DS was isolated for further complete structural characterization. Agarose-gel electrophoresis in combination with various enzymes, chondroitin ABC lyase, chondroitin B lyase, chondroitin ACII lyase from Arthrobacter aurescens, and chondroitin AC lyase from Flavobacterium heparinum, confirmed the DS nature of this polysaccharide. Furthermore, by evaluating the unsaturated disaccharides produced by the action of the various lyases, this natural polymer was found to be composed of approx. 75% of disaccharides containing iduronic acid (IdoA) mainly found in disaccharides monosulfated in position 4 of N-acetylgalactosamine (GalNAc) and disulfated in position 2 of the IdoA and 4 of GalNAc (disaccharide B typical of DS). In contrast, glucuronic acid was found to be mainly associated with the nonsulfated disaccharide (approx. 92%), while the rest formed low percentages of monosulfated disaccharides in position 4 or 6 of GalNAc preferentially located inside the chains. Generally, this GAG possesses a peculiar structure, due to the presence of significant amounts of nonsulfated disaccharide mainly located close to the nonreducing end, to the elevated percentage of the disaccharide B, and to the presence of not previously reported low amounts of the disaccharide monosulfated in position 2 of the uronic acid. S. inaequivalvis DS was also found to have a mean molecular mass of approx. 27,000 Da and a mean charge density of 1.10 that increases to 1.54 for the carbohydrate backbone composed of IdoA residues. (1)H-NMR and (13)C-NMR analyses confirmed the nature of S. inaequivalvis polymer revealed by the presence of signals related to DS corresponding to the residue of IdoA and GalNAc mainly sulfated at the C4 along with the presence of a signal belonging to the residue of H1 IdoA-2SO(4). S. inaequivalvis DS was further depolymerized by partial controlled digestion with chondroitinase ABC and separated into oligosaccharides by online HPLC/ESI-MS to obtain sequence information. The most prominent generated oligosaccharides comprised the repeating unit Delta Hex-GalNAcSO(4) thus confirming the results obtained by disaccharide analysis and the structures of the major oligosaccharides (from 6- to 10-mer) confirmed, by means of the LC-MS, the presence of approx. 20% of nonsulfated disaccharide. Furthermore, a minor but significant percentage of a monosaccharide having an m/z 300 and corresponding to GalNAcSO(4) belonging to the DS nonreducing end was observed along with saturated hexasaccharide derived from the nonreducing terminus of the intact DS ending with a uronic acid residue. Finally, S. inaequivalvis DS was calculated to possess a high heparin cofactor II activity of 169.2 +/- 10.7% fairly similar to that of several DS samples purified from porcine and bovine tissues.

Understanding Lead Chemistry from Topological Insights: The Transition between Holo‐ and Hemidirected Structures within the [Pb(CO)n]2+ Model Series

In this contribution, we focus to the currently unknown [Pb(CO)(n)](2+) model series (n=1 to 10), a set of compounds which allows us to investigate in-depth the holo- and hemidirectional character that lead complexes can exhibit. By means of DFT computations performed using either relativistic four-component formalisms coupled to all-electron basis sets for [Pb(CO)](2+), [Pb(OC)](2+) and [Pb(CO)(2)](2+), or scalar relativistic pseudopotentials for higher n values, the structure and the energetics of these species are investigated. The results are complemented by Constrained Space Orbital Variations (CSOV) and Electron Localization Function (ELF) comprehensive analyses in order to get better insights into the poorly documented chemical fundamentals of the Pb(2+) cation. Whereas the discrimination between holo- and hemidirected structures is usually done according to the geometry, we here provide a quantitative indicator grounded on <rho>(V(Pb)), the mean charge density of the valence monosynaptic V(Pb) ELFic basin associated to the metal cation. Free-enthalpy relying discussions show, moreover, that those gas-phase complexes having n=7, 8 or 9 may be experimentally instable and should dissociate into [Pb(CO)(6)](2+) and a number of CO ligands. According to second-order differences in energy, it is anticipated that the n=3 or 6 structures should be the most probable structures in the gas phase. Gathering all data from the present theoretical study allows us to propose some concepts that the versatile structural chemistry of Pb(2+) complexes could rely on.

Oral absorption and bioavailability of ichthyic origin chondroitin sulfate in healthy male volunteers

Objective: Chondroitin sulfate (CS) has proven to be a valuable therapeutic tool as a symptomatic slow-acting drug for the treatment of osteoarthritis after oral administration. The aim of this study was to assess the absorption of CS of ichthyic origin after oral administration to 20 healthy male volunteers. Design: Ichthyic origin CS (from shark cartilage, 4 g) was orally administered to 20 healthy human volunteers, and then extracted and purified from plasma over a 48 h period. The polysaccharide absorbed by oral route was characterized and quantified by agarose-gel electrophoretic technique, and densitometric scanning. In addition, the percentage of constituent disaccharides and charge density were measured. Results: After oral administration, ichthyic CS plasma levels increased (more than 120%) with a peak concentration at 8.7 h, with the increase reaching significance from 4 to 16 h. A significant decrease in the relative amount of non-sulfated disaccharide was measured (reaching the minimum relative percentage of 30.86±20.79% at 8 h). At the same time, 4-sulfated disaccharide increased to a maximum of 51.91±25.91% at 6 h, and 6-sulfated and disulfated disaccharides appeared in blood, reaching maximum concentrations of 15.24±16.60% at 8 h and 2.93±4.82% at 12 h, respectively. Concomitantly, the mean charge density rose from 0.40±0.14 at predose to a maximum of 0.72±0.22 and 0.72±0.21 measured 8 and 12 h after ichthyic CS administration. Conclusions: Ichthyic CS is absorbed slowly, with a t max =8.7±4.5 h and the C maxaveraged 4.87±2.05 μg/ml. The differences in the absorption and bioavailability of the various CS formulations is strongly influenced by the structure and characteristics, such as molecular mass, charge density, and cluster of disulfated disaccharides, of the parental molecules.

Oral bioavailability of chondroitin sulfate (Condrosulf ®) and its constituents in healthy male volunteers

Objective Drug treatment of osteoarthritis (OA) includes symptomatic slow-acting drugs (SYSADOA). This class of compounds have a slow onset of action and improve OA symptoms. Among the SYSADOA, Condrosulf ® (manufactured by IBSA), whose active ingredient is chondroitin sulfate, has proven to be a valuable therapeutic tool for the symptomatic treatment of OA after oral administration. The aim of this study was to assess the bioavailability of chondroitin sulfate and its constituents after oral administration of Condrosulf ® to 20 healthy male volunteers. Pharmacokinetic parameters and the structure and properties of plasma chondroitin sulfate were determined after administration of Condrosulf ®. The possible physiological regulation of plasma levels of endogenous chondroitin sulfate during the day was also assessed. Design Condrosulf ® (composed of bovine origin chondroitin sulfate, 4 g) was orally administered to 20 healthy human volunteers, and chondroitin sulfate derivatives were extracted and purified from plasma over a 48 h period. Polysaccharide fractions absorbed by oral route were characterized and quantified by agarose-gel electrophoretic technique, and densitometric scanning. In addition, the percentage of constituent disaccharides and charge density were measured in an effort to physico-chemically characterize chondroitin sulfate fractions absorbed per os. Results Plasma levels of endogenous chondroitin sulfate were detectable in all subjects, and the mean values calculated on six subjects varied during the day from 0.3 to 5.3 μg/ml. After administration of Condrosulf ®, chondroitin sulfate plasma levels increased (more than 200%) in all subjects with a peak concentration after 2 h, with the increase reaching significance from 2 to 6 h. Absorption of exogenous chondroitin sulfate was also proved by the change in the composition of disaccharides in plasma after drug administration with respect to baseline. A significant decrease in the relative amount of non-sulfated disaccharide was measured (reaching the minimum relative percentage of 22.96±11.68% at 4 h). At the same time 4-sulfated disaccharide increased to a maximum of 60.50±10.45% after 4 h and 6-sulfated disaccharide appeared in blood, reaching a maximum concentration of 17.33±6.52% after 2 h. Concomitantly the mean charge density increased from 0.40±0.09 at pre-dose to a maximum of 0.78±0.11 4 h after Condrosulf ® administration. As for safety, the treatment was well tolerated and did not determine any relevant change in vital signs nor ECG. Conclusions From this study and literature data, it appears that exogenous chondroitin sulfate (Condrosulf ®) is absorbed as a high molecular mass polysaccharide together with derivatives resulting from a partial depolymerization and/or desulfation. Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.

Conformation of Polyelectrolyte Chains in Dilute Aqueous Solutions Investigated by Conductometry, 3. Influence of Charge Density on the Conformation of Partly Alkylated Poly(N-ethyl-4-vinylpyridinium) Cations and Ionenes

The temperature dependencies of the conductivities of dilute salt-free aqueous solutions of partly alkylated poly(N-ethyl-4-vinylpyridinium) bromides (PEVP-β) and 2,n-ionene bromides with different degrees of polymerization (DP) were obtained. The charge density of the polycations was varied over a wide range by using PEVP-β with different degrees of alkylation β (%) in the range 25 < β < 95, and 2,n-ionenes with n values of 4, 8, and 10. On the basis of Manning's polyelectrolyte theory, the mean charge spacing (b) of the chains was calculated from these data. For the shortest PEVP-β chains, DP = 20, changing β had only a negligible effect on b in the whole β range studied. In contrast, the b values of the highly polymerized samples dropped significantly upon decrease of β in the range 95 > β > 60 indicating folding of the chains upon decrease of their charge density. Folding was supported by the fact that the persistence length of PEVP-95 estimated from the obtained dependency of b on DP far exceeded the estimated persistence lengths of PEVP-60 and 2,4-ionene having similar mean charge densities. Further decrease of β at β < 60 caused noticeable growth of b with a pronounced trend of convergence of the curves of all studied PEVP-β samples. These findings might be attributed to the conformational changes of the chains considered in the context of the scaling theory of polyelectrolytes. The obtained results suggest that the revealed trend in conformational changes of the chains upon variation of their charge density is common, irrespective of whether PEVP-β with a random distribution of the charges along the chains or ionenes with the regular charge distribution are under consideration.

Effects of zinc on cell proliferation and proteoglycan characteristics of epiphyseal chondrocytes.

Zinc has been postulated as an important nutritional factor involved in growth promotion; however, the cellular mechanisms involved in the effects of zinc on linear growth remain to be elucidated. This study was conducted to evaluate the effects of zinc on the proliferation rate of epiphyseal growth plate chondrocytes and on the structural characteristics of the proteoglycans synthesized by these cells. For these purposes, hypertrophic and proliferating chondrocytes were isolated from the tibiae of 1- and 5-week-old chickens, respectively. Chondrocytes were cultured under serum-free conditions and primary cultures were used. The results showed that zinc stimulated proliferation by 40-50% above the baseline in the case of proliferating chondrocytes, but it had no effect on hypertrophic chondrocytes. Zinc had neither any effects on mean charge density of proteoglycans synthesized by hypertrophic chondrocytes nor in their hydrodynamic size. In contrast, zinc induced an increase in mean charge density and a decrease of hydrodynamic size of proteoglycans synthesized by proliferating chondrocytes. In both cell types zinc had no effect on the composition and hydrodynamic size of the glycosaminoglycan chains. The increased ability of proliferating chondrocytes cultured in the presence of zinc to synthesize 3'-phosphoadenosine 5'-phosphosulfate (PAPS) could be explained by the induction of enzymes participating in the sulfation pathway of proteoglycans. Therefore, the increase in mean charge density of proteoglycans observed in this study may be explained by an increase of the degree of sulfation of proteoglycan molecules. We speculate that the effect of zinc on linear growth may be explained at a cellular level by: a) an increase in proliferation rates of proliferating chondrocytes, and b) increased synthesis of highly charged proteoglycan molecules which decreases mineralization.

Sodium fluoride induces changes on proteoglycans synthesized by avian osteoblasts in culture.

The results reported here show that sodium fluoride (NaF) at low concentration (up to 10 microM) increased four times the proliferation rate of avian osteoblasts in culture. Also NaF increases, in a concentration dependent manner, 10 times the alkaline phosphatase activity. However, NaF decreased the incorporation of 35S-sulfate into proteoglycans (PGs) synthesized by osteoblasts (60-65%). Also, we observed that PGs synthesized in the presence of NaF (50 microM) exhibited a higher sensitivity to chondroitinase ABC than PGs synthesized by osteoblasts in the absence of NaF, suggesting an increase in the chondroitin sulfate moieties associated with the core protein of PGs. The modification of glycosaminoglycan (GAG) chains composition was evidenced also by change in the mean charge density of the PGs observed by ion exchange chromatography. Since the ratio of 35SO4/3H-glucosamine incorporated into PGs was similar in the presence and in the absence of NaF (8.2 and 7, respectively), it is not possible to explain differences in mean charge density by changes in the sulfation extent of PGs. No differences were observed in the hydrodynamic size of PG synthesized in the presence of NaF, nor in the hydrodynamic size of the GAG chains. According to these results, we speculate that the stimulatory effect of fluoride on bone mineralization may be mediated, in part, by the changes in the rate of synthesis or in the structural characteristics of bone PGs. The changes produced by fluoride in PGs suggest that these molecules play an inhibitory role in the bone mineralization process.