Cytokines and growth factors in a biologic product obtained from patients' urine as immune-modulators to treat autoimmune and allergic diseases.

At "Instituto de Alergias y Autoinmunidad Dr. Maximiliano Ruiz Castañeda, A.C." in Mexico City, a non-traditional health care center focused on the treatment of autoimmune and allergic diseases using personalized medicine, an alternative treatment referred to as an "immune-modulator" has been developed. In this study, we will refer to this treatment substance as the "immune-modulator." In brief, a urine sample is collected from the patient and processed to obtain the peptide fraction, which is conditioned and then administered sublingually to the patient. Sample processing involves multiple steps aimed at the removal of toxic compounds and enrichment for cytokines, growth factors, and other immune peptides that may contribute to the function of the immune-modulator. This treatment has been administered for many years, and patients testify that it is useful and reliable. Despite the benefits of this treatment, the molecular mechanisms underlying its effects have not been thoroughly investigated. Therefore, this study aims to identify immunoregulatory peptides, such as cytokines and growth factors, in the immune-modulator. Urine and immune-modulator concentrations of cytokines and growth factors were assessed using a Luminex assay. Twenty-one cytokines and growth factors were identified in immune-modulator samples. MCP-1 was identified in 100% of the samples; MIP-1ß, IL-8, RANTES, INF-γ, and IP-10 were identified in approximately 65-70% of samples; IL5, IL-1B, and IL-17 in 50-60%; eotaxin, VEGF, IL-6, and FGF in about 40%; MIP-1α, IL-9, GM-CSF, G-CSF, IL-12, and IL-15 in about 20-30%; and IL-13 and PDGF-bb were identified in <6% of samples. Additionally, patients exhibited significant changes in IL-1ß, IFN-γ, and MCP-1 concentrations after treatment with the immune-modulator, whereas healthy individuals showed no significant change in response to the treatment. The immune-modulator is an alternative treatment based on the administration of cytokines and growth factors obtained from the urine of patients. In this study, its composition was characterized. The isolated products could be responsible for the effects of the immune-modulator. Further trials are required to evaluate the effective delivery of these molecules by the administration route described.

Multiionic effects on the capacitance of porous electrodes.

The rapid and reversible ionic electrosorption in the electrical double layers (EDLs) of moderately charged micropores in contact with a solution is the main concept underlying capacitive energy and desalination devices. For the usual operating conditions, the ion concentration is large enough for the confinement of ions to play an important role in their distribution in the EDL. On the other hand, although most laboratory experiments have been carried out with simple salt solutions, realistic applications require a proper analysis of the effect of the different ionic species existing in natural waters. Here we focus on the role of multiionic solutions on the double layer structure. For this purpose, a model is presented in which the EDL overlap and the existence of a Stern layer are considered. It is also taken into account that the ions can be tightly packed by using the Carnahan-Starling model. This model is applied to analyze the structure of the EDL with multiionic solutions containing divalent ions. The predictions of this model are found to largely differ from those of the better known Bikerman equation, and are more realistic. It is demonstrated that the presence of tiny amounts of divalent ions in the bulk is enough to dominate the EDL behavior, and hence, its capacitance, energy storage, and desalination properties.

MHC2TA and FCRL3 genes are not associated with rheumatoid arthritis in Mexican patients.

Rheumatoid arthritis (RA) is a multifactorial disease. A combination of genetic and environmental risk factors contributes to its etiology. Several genes have been reported to be associated with susceptibility to the development of RA. The MHC2TA and FCRL3 genes have been associated previously with RA in Swedish and Japanese populations, respectively. In two recent reports, we show an association between FCRL3 and juvenile rheumatoid arthritis (JRA), and MHC2TA and acute coronary syndrome (ACS) in Mexican population. We assessed the association between three single nucleotide polymorphisms (SNPs) of the MHC2TA (-168G/A; rs3087456, and +16G/C; rs4774) and FCRL3 (-169T/C; rs7528684) genes and rheumatoid arthritis in Mexican population through a genotyping method using allelic discrimination assays with TaqMan probes. Our case-control study included 249 patients with RA and 314 controls. We found no evidence of an association between the MHC2TA -168G/A and +1614G/C or FCRL3 -169T/C polymorphisms and RA in this Mexican population. In this cohort of Mexican patients with RA, we observed no association between the MHC2TA or FCRL3 genes and this autoimmune disease.

Polyelectrolyte-coated carbons used in the generation of blue energy from salinity differences.

In this work we present a method for the production of clean, renewable electrical energy from the exchange of solutions with different salinities. Activated carbon films are coated with negatively or positively charged polyelectrolytes using well-established adsorption methods. When two oppositely charged coated films are placed in contact with an ionic solution, the potential difference between them will be equal to the difference between their Donnan potentials, and hence, energy can be extracted by building an electrochemical cell with such electrodes. A model is elaborated on the operation of the cell, based on the electrokinetic theory of soft particles. All the features of the model are experimentally reproduced, although a small quantitative difference concerning the maximum open-circuit voltage is found, suggesting that the coating is the key point to improve the efficiency. In the experimental conditions used, we obtain a power of 12.1 mW m(-2). Overall, the method proves to be a fruitful and simple approach to salinity-gradient energy production.

Electrokinetic and dielectric response of a concentrated salt-free colloid: Different approaches to counterion finite-size effects.

In the present work, a general model is developed for the electrokinetics and dielectric response of a concentrated salt-free colloid that takes into account the finite size of the counterions released by the particles to the solution. The effects associated with the counterion finite size have been addressed using a hard-sphere model approach elaborated by Carnahan and Starling [N. F. Carnahan and K. E. Starling, Equation of state for nonattracting rigid spheres, J. Chem. Phys. 51, 635 (1969)0021-960610.1063/1.1672048]. A more simple description of the finite size of the counterions based on that by Bikerman has also been considered for comparison. The studies carried out in this work include predictions on the effect of the finite counterion size on the equilibrium properties of the colloid and its electrokinetic and dielectric response when it is subjected to constant or alternating electric fields. The results show how important the counterion finite-size effects are for most of the electrokinetic and dielectric properties of highly charged and concentrated colloids, mainly for the static and dynamic electrophoretic mobilities. Furthermore, new insights are provided on the counterion condensation effect when counterions are allowed to have finite size. Focus is placed on the changes undergone by their concentration in the condensation layer for low-salt and highly charged colloids.

Electrokinetic detection of the salt-free condition in colloids. Application to polystyrene latexes.

Because of their singular phenomenology, the so-called salt-free colloids constitute a special family of dispersed systems. Their main characteristic is that the dispersion medium ideally contains only the solvent and the ions compensating exactly the surface charge of the particles. These ions (often called released counterions) come into the solution when the surface groups responsible for the particles charge get ionized. An increasing effort is nowadays dedicated to rigorously compare theoretical model predictions for ideal salt-free suspensions, where only the released counterions are supposed to be present in solution, with appropriately devised experiments dealing with colloids as close as possible to the ideal salt-free ones. Of course, if the supporting solution is aqueous, the presence of atmospheric contamination and any other charged species different from the released counterions in the solution must be avoided. Because this is not an easy task, the presence of dissolved atmospheric CO2 and of H+ and OH- from water dissociation cannot be fully discarded in aqueous salt-free solutions (often denominated realistic in such case). Ultimately, at some point, the role of the released counterions will be comparable or even larger in highly charged concentrated colloids than that of added salts. These topics are covered in the present contribution. The model results are compared with experimental data on the dynamic mobility and dielectric dispersion of polystyrene spheres of various charges and sizes. As a rule, it is found that the model correctly predicts the significance of alpha and Maxwell-Wagner-O'Konski relaxations. Positions and amplitudes of such relaxations are well predicted, although it is necessary to assume that the released counterions are potassium or sodium instead of protons, otherwise the frequency spectra of experimental mobility and permittivity differ very significantly from those theoretically calculated. The proposed electrokinetic evaluation is an ideal tool for detecting in situ the possible contamination (or incomplete ion exchange of the latexes). A satisfactory agreement is found when potassium counterions are assumed to be in solution, mostly if one considers that the comparison is carried out without using any adjustable parameters.

Role of surface conductivity in the dynamic mobility of concentrated suspensions.

In this article, a cell model is used for the evaluation of the alternating current (ac) mobility (dynamic mobility) of spherical particles in suspensions of arbitrary volume fractions of solids. The main subject is the consideration of the role of the electrical conductivity (SLC or K(sigmai)) of the stagnant layer (SL) on the mobility. It is assumed that the total surface conductivity (K(sigma)), resulting from both K(sigmai) and the diffuse layer conductivity (K(sigmad)), is constant in the cases considered and that it is the K(sigmai)-K(sigmad) balance that determines the SL effects. We first explore the effect of K(sigmai) on the frequency dependence of the dynamic mobility. It is found that the mobility decreases on average, for any frequency, when K(sigmai) increases. This is a consequence of stagnancy: ions in the SL, although contributing to the surface conductivity, do not drag liquid with them when they migrate and do not contribute to electro-osmotic flow or, equivalently, to electrophoresis. Three relaxations are observed in the mobility-frequency spectrum: inertial (the particle and liquid motions are hindered), Maxwell-Wagner-O'Konski (ions in the double layer cannot follow the field oscillations and can move only over a distance much smaller that the diffuse layer thickness), and the so-called alpha or concentration polarization process (the ions can rearrange around the particle, but they cannot form the electrolyte concentration field that appears at low frequency). Whereas the first two relaxations are little affected by K(sigmai), the alpha process undergoes significant changes. Thus, the mobility increases with frequency around the alpha relaxation region if K(sigmai) is negligible, but it decreases with frequency in the same interval if K(sigmai) is finite. With the aim of explaining this behavior, we calculate the capillary osmosis velocity field that is the fluid flow provoked by the concentration gradient around the particle. The calculations presented demonstrate that the velocity is reduced (for each frequency and position) when the SLC is raised. It is proposed that such a decrease adds to that due to the changes in the induced dipole moment of the particle, also favoring a decrease in the mobility. These tendencies are also present when the volume fraction of solids, phi, is modified, although higher phi values somewhat hide the effect of K(sigmai), as in fact observed with all features of electrokinetics associated with the phenomenon of concentration polarization.

Field-induced clearing in sphere-sphere and rod-sphere binary mixtures of charged colloidal particles.

Binary mixtures of larger and smaller colloids having charges of equal sign display unusual response to low-frequency electric fields. We show here that the previously reported negative torque acting on rodlike particles when in presence of a sea of smaller particles is accompanied by a field-induced clearing of the suspension. Measurements of transmitted intensity performed on mixtures of large (dilute) and small (semidilute) spherical particles indicate that such a clearing effect is universal and due to an anisotropic E2 -dependent redistribution of the small spheres around the large ones. We interpret this behavior as resulting from O(E2) electro-osmotic flows whose magnitude is greatly enhanced by the presence of the small particles.

[Volunteer satisfaction: Internal structure and relationship with permanence in organizations]. / Satisfacción en el voluntariado: estructura interna y relación con la permanencia en las organizaciones.

Volunteer satisfaction: Internal structure and relationship with permanence in organizations. The concept of satisfaction is considered theoretically relevant in practically all the studies that have investigated the factors that influence the permanence of volunteer participation in organizations. However, the practical results are not conclusive, perhaps due to the wide range of ways in which the concept is understood and measured. The object of this study is: to analyse the internal structure of satisfaction and to verify its relationship with volunteer duration in organizations. The results of the factor analysis yield a three-factor structure: Satisfaction with the management of the organization, Satisfaction with the tasks, Satisfaction of motivations. The three factors allow us to differentiate between individuals who remain in the organization for a period of 12 consecutive months, and those who leave earlier. The results of structural equation model analysis show that the relationship between satisfaction and the length of time that volunteers stay with the organization is affected by the intention to remain.

Hereditary xanthinuria. Evidence for enhanced hypoxanthine salvage.

We tested the hypothesis that there is an enhanced rate of hypoxanthine salvage in two siblings with hereditary xanthinuria. We radiolabeled the adenine nucleotide pool with [8-14C]adenine and examined purine nucleotide degradation after intravenous fructose. The cumulative excretion of radioactivity during a 5-d period was 9.7% and 9.1% of infused radioactivity in the enzyme-deficient patients and 6.0 +/- 0.7% (mean +/- SE) in four normal subjects. Fructose infusion increased urinary radioactivity to 7.96 and 9.16 X 10(6) cpm/g creatinine in both patients and to 4.73 +/- 0.69 X 10(6) cpm/g creatinine in controls. The infusion of fructose increased total urinary purine excretion to a mean of 487% from low-normal baseline values in the patients and to 398 +/- 86% in control subjects. In the enzyme-deficient patients, the infusion of fructose elicited an increase of plasma guanosine from undetectable values to 0.7 and 0.9 microM. With adjustments made for intestinal purine loss, these data support the hypothesis that there is enhanced hypoxanthine salvage in hereditary xanthinuria. Degradation of guanine nucleotides to xanthine bypasses the hypoxanthine salvage pathway and may explain the predominance of this urinary purine compound in xanthinuria.

Surface conductivity of colloidal particles: experimental assessment of its contributions.

In this work we investigate how combined data on dielectric dispersion and electrophoretic mobility of colloidal suspensions at different temperatures can be used to evaluate the two main quantities characterizing the solid/liquid interface, namely, the zeta potential and the stagnant layer conductivity (SLC). This is possible because the electric permittivity depends on the total surface conductivity, while the electrophoretic mobility is governed by both the zeta potential and that conductivity. Based on a simple analytical theory, we can also estimate the diffusion coefficient of counterions in the stagnant layer, D(SL), for each temperature. The results lead to a good agreement between theory and experiment, although with somewhat high values of D(SL). With the aim of improving this description, we use a full theory of the electric permittivity of suspensions that accounts for the existence both of SLC and of a finite volume fraction of solids. An excellent description of the whole dielectric spectrum and of the electrophoretic mobility is possible in this case, although with still overestimated diffusion coefficients. This fact is discussed, and the importance of considering particle concentration effects even for suspensions that are often considered dilute is also stressed.

Electrokinetics in extremely bimodal suspensions.

Prompted by the results obtained by Mantegazza et al. [Nature Physics 1 (2005) 103], where the electric birefringence of suspensions of elongated particles was strikingly affected by the presence of a sea of very small (size ratio lower than 10:1) colloidal spheres, we have undertaken an investigation of other electrokinetic phenomena in suspensions containing various relative concentrations of large (Teflon or polystyrene latex) and small (nanometer-sized silica spheres) colloids. We have determined the quantities that might be greatly affected by the size distribution of the particles, mainly in the presence of ac electric fields, since the response of the suspensions will show very characteristic relaxations, dominated in principle by the size of the particles. In this work, we report on measurements of the dielectric dispersion of mixed particles as a function of the concentration, ionic strength, and field frequency. The results indicate that the response is not just a simple combination of those obtained with suspensions of the individual particles, and in fact the presence of even small amounts of the small particles affects considerably the frequency response of the suspensions.

Dynamic electrophoretic mobility and electric permittivity of concentrated suspensions of plate-like gibbsite particles.

In this paper we present experimental results on the electrokinetic behavior of planar gibbsite particles in concentrated suspensions. The dc electrophoretic mobility measurements are in this case of little significance, as they are scarcely informative. In the present investigation, we show that the dielectric dispersion and dynamic electrophoresis can in contrast provide such information. The complicating factors are of course the non-spherical shape and the finite particle concentration, as no complete theory of these phenomena exists for such systems. We propose to use first of all a model of dynamic electrophoresis of spheroids in which the effect of volume fraction is considered by means of an approximate theory previously obtained for spheres, based on the evaluation of electrical and hydrodynamic interactions between particles. In addition, the role of volume fraction on the high frequency inertial relaxation is also ascertained and used to obtain a volume fraction-independent radius of the gibbsite spheroids. A similar approach is used for the evaluation of dielectric dispersion data. Both the dynamic mobility and dielectric constant dependencies on frequency were obtained for gibbsite suspensions of different volume fractions in 0.5mMKCl. The theoretical treatments elaborated were applied to these data, and a coherent picture of the geometrical and electrical characteristics of the particles was obtained.

Optical and electro-optical derivation of the pretransitional behavior of orientational and shear viscosities in the isotropic phase of liquid crystals.

The pretransitional equilibrium properties of isotropic liquids in the proximity of the isotropic-nematic phase transition are well known and successfully modeled. Much less is known about the dynamic behavior, and in particular about the pretransitional viscosity. In this work we combine two techniques [dynamic light scattering (DLS) and electric birefringence spectroscopy (EBS)] offering complementary insights into both static and dynamic pretransitional behavior of the homologous nCB family (n-alkyl cyanobiphenyl). EBS explores the single molecule flipping dynamics retarded by a paranematic potential barrier and enables extracting the associated transport coefficient, which is found to be of Arrhenius type in the whole temperature range explored. DLS reflects the collective dynamics of correlated domains and depends on the viscous damping of the orientational order. Such a viscosity displays Arrhenius behavior only sufficiently far from the transition temperature, with deviations growing as a power law of the appropriate reduced temperature with exponents around 0.1.

The functional PTPN22 C1858T polymorphism confers risk for rheumatoid arthritis in patients from Central Mexico.

Rheumatoid arthritis (RA) is a complex genetic disease. Human leukocyte antigen (HLA) and non-HLA genes are reportedly associated with an increased risk of RA. The protein tyrosine phosphatase non-receptor 22 gene (PTPN22), which encodes the lymphoid tyrosine phosphatase (LYP) protein, is one of the best examples of a non-HLA gene associated with a risk for RA in several populations. The functional PTPN22 C1858T (R620W) non-synonymous polymorphism is widely associated with an increased risk for RA in Europeans and non-Europeans. The aim of this study was to determine if the PTPN22 C1858T polymorphism confers susceptibility to RA in a sample of patients from Mexico. This study included 364 RA patients and 387 non-related controls from Central Mexico. Genotyping of the PTPN22 C1858T (rs2476601) polymorphism was performed using allelic discrimination assays with TaqMan probes. The functional PTPN22 C1858T polymorphism was associated with an increased risk for RA in our study population. The CC vs CT genotype in RA patients versus healthy controls had an odds ratio (OR) of 4.17 (95 % CI 1.79-9.74, p = 0.00036), while T allele had an OR of 4.06 (95 % CI 1.75-9.41, p = 0.00043). PTPN22 is a genetic risk factor for developing RA in the Mexican population.

Influence of cell-model boundary conditions on the conductivity and electrophoretic mobility of concentrated suspensions.

In the last few years, different theoretical models and analytical approximations have been developed addressing the problem of the electrical conductivity of a concentrated colloidal suspension. Most of them are based on the cell model concept, and coincide in using Kuwabara's hydrodynamic boundary conditions, but there are different possible approaches to the electrostatic boundary conditions. We will call them Levine-Neale's (LN, they are Neumann type, that is they specify the gradient of the electrical potential at the boundary), and Shilov-Zharkikh's (SZ, Dirichlet type). The important point in our paper is that we show by direct numerical calculation that both approaches lead to identical evaluations of the conductivity of the suspensions if each of them is associated to its corresponding evaluation of the macroscopic electric field. The same agreement between the two calculations is reached for the case of electrophoretic mobility. Interestingly, there is no way to reach such identity if two possible choices are considered for the boundary conditions imposed to the field-induced perturbations in ionic concentrations on the cell boundary (r = b), deltan(i) (r = b). It is demonstrated that the conditions deltan(i)(b) = 0 lead to consistently larger conductivities and mobilities. A qualitative explanation is offered to this fact, based on the plausibility of counter-ion diffusion fluxes favoring both the electrical conduction and the motion of the particles.

Determination of stagnant layer conductivity in polystyrene suspensions: temperature effects.

In the classical theory of electrokinetic phenomena, it is admitted that the whole electrokinetic behavior of any colloidal system is fully determined by the zeta potential, zeta, of the interface. However, both experimental data and theoretical models have shown that this is an incomplete picture, as ions in the stagnant layer (the region between the solid surface and the slip plane--the plane where the equilibrium potential equals zeta) may respond to the field. In this paper, we aim at the evaluation of this contribution by the estimation of both K(SL)(sigma) (the surface conductivity of the stagnant layer) and K(d)(sigma) (the conductivity associated with the diffuse layer). This will be done by measuring the high-frequency dielectric dispersion (HFDD) in polystyrene suspensions; here "high-frequency" means the frequency interval where Maxwell-Wagner-O'Konski relaxation takes place (typically at MHz frequencies). Prior to any conclusions, a treatment of electrode polarization effects in the measurements was needed: we used two methods, and both led to similar results. Simulating the existence of surface conductivity by bulk conductivity, we reached the conclusion that no consistent explanation can be given for our HFDD and additional electrophoresis data based on the existence of diffuse-layer conductivity alone. We thus show how K(SL)(sigma) can be estimated and demonstrate that it can be explained by an ionic mobility very close to that characteristic of ions in the bulk solution. Such mobility, and hence also the values of K(SL)(sigma), increases with temperature as expected on simple physical grounds.

Female gout. Clinical spectrum and uric acid metabolism.

We reviewed the clinical features and uric acid metabolism in 37 female patients with gout. In 32 female patients (86%), gout was diagnosed after menopause. Among the five premenopausal patients, four had renal insufficiency and one had superactivity of phosphoribosylpyrophosphate synthetase. More than 50% of the female patients had osteoarthritis, hypertension, or renal insufficiency or were treated with diuretics. Comparison with 220 male patients with gout showed that female patients developed gout significantly later, more frequently had associated diseases, and more often were receiving diuretics, whereas significantly more male than female patients had alcoholism. The articular features of gout were similar in both groups. However, the prevalence of tophi was higher and its localization different in female than in male patients. Female patients with gout had a higher mean serum urate concentration and a lower mean urinary uric acid excretion than did male patients with gout. These differences were significant and independent of the effects of age, renal insufficiency, alcoholism, or previous diuretic intake. Renal underexcretion of uric acid appears to be more severe in female than in male patients with gout.