Emilio Rubín de Celis

Synergistic encapsulation of the anti-HIV agent efavirenz within mixed poloxamine/poloxamer polymeric micelles

This study investigated the synergistic performance of mixed polymeric micelles made of linear and branched poly(ethylene oxide)-poly(propylene oxide) for the more effective encapsulation of the anti-HIV drug efavirenz. The co-micellization process of 10% binary systems combining different weight ratios of a highly hydrophilic poloxamer (Pluronic F127) and a more hydrophobic poloxamine counterpart (Tetronic T304 and T904) was investigated by means of dynamic light scattering, cloud point and electronic spin resonance experiments. Then, the synergistic solubilization capacity of the micelles was shown. Findings revealed a sharp solubility increase from 4 μg/ml up to more than 33 mg/ml, representing a 8430-fold increase. Moreover, the drug-loaded mixed micelles displayed increased physical stability over time in comparison with pure poloxamine ones. Overall findings confirmed the enormous versatility of the poloxamer/poloxamine systems as Trojan nanocarriers for drug encapsulation and release by the oral route and they entail a relevant enhancement of the previous art towards a more compliant pediatric HIV pharmacotherapy.

Regulation of functional and regressing stages of corpus luteum development in mice. Role of reactive oxygen species

The endocrine and immune systems modulate ovarian function. The aim of the present work was to compare the status of various modulating factors in two well-defined stages of corpus luteum (CL) development (the functional stage and the regressing stage) by means of a gonadotropin-synchronised mouse model. At the regressing stage of CL development, we found that ovarian tissue showed increased prostaglandin (PG) F(2alpha) and diminished PGE levels concomitantly with enhanced protein abundance of ovarian cyclooxygenase 2, the inducible isoform of the limiting enzyme of PG synthesis. We also found both enhanced lipid peroxidation and enhanced total superoxide dismutase activity, as well as inhibited catalase activity and inhibited total hydroxyl radical scavenger capacity, when compared with ovaries at the functional stage. In addition, at the regressing stage we observed an increased percentage of CD8+ (cytotoxic/suppressor) T-cells and a decreased percentage of CD4+ (helper) T-cells from ovarian-draining lymph nodes. Also, the serum interleukin (IL)-2, IL-4 and IL-10 were diminished as compared with the functional stage. We conclude that a pro-oxidant status together with a pro-inflammatory response is responsible for the loss of luteal function.

Effects of photooxidation on membrane integrity in Salix nigra seeds

BACKGROUND AND AIMS Salix nigra seeds are desiccation-tolerant, as are orthodox seeds, although in contrast to other orthodox seeds they lose viability in a few weeks at room temperature. They also differ in that the chloroplasts of the embryo tissues conserve their chlorophyll and endomembranes. The aim of this paper was to investigate the role of chlorophyll in seed deterioration. METHODS Seeds were aged at different light intensities and atmospheric conditions. Mean germination time and normal and total germination were evaluated. The formation of free radicals was assessed using electronic spin resonance spectroscopy, and changes in the fatty acid composition from phospholipids, galactolipids and triglycerides using gas-liquid chromatography. Membrane integrity was studied with electronic spin resonance spin probe techniques, electrolyte leakage and transmission electron microscopy. KEY RESULTS Light and oxygen played an important role in free-radical generation, causing a decrease in normal germination and an increase in mean germination time. Both indices were associated with a decrease in polyunsaturated fatty acids derived from membrane lipids as phospholipids and galactolipids. The detection of damage in thylakoid membranes and an increase in plasmalemma permeability were consistent with the decrease in both types of lipids. Triglycerides remained unchanged. Light-induced damage began in outermost tissues and spread inwards, decreasing normal germination. CONCLUSIONS Salix nigra seeds were very susceptible to photooxidation. The thylakoid membranes appeared to be the first target of the photooxidative process since there were large decreases in galactolipids and both these lipids and the activated chlorophyll are contiguous in the structure of that membrane. Changes in normal germination and mean germination time could be explained by the deteriorative effects of oxidation.

Influence of serum protein and albumin addition on the structure and activity of an exogenous pulmonary surfactant

The comparative analysis of the deleterious action of albumin and total serum proteins (SP) might help to understand the nature of the interaction surfactant--SP. This study evaluated the effects of serum proteins and albumin on bulk shear viscosity, surface tension, surface area reduction, and the ratio between the light and heavy subtypes of surfactant suspensions. Our results showed a correlation between the bulk viscosity and aggregation degree of surfactant suspensions. The addition of albumin or SP induced the transformation from the heavy to the light subtype, reducing the viscosity. SP caused disaggregation and inactivation, whereas albumin caused only disaggregation without loss of surface activity. When SP were removed, the heavy fraction obtained recovered its surface activity. We conclude that the disaggregation may not be the primary cause for the loss of surface activity. Surfactant inactivation by a serum component, different from albumin, would be probably due to a physical interaction, a phenomenon that is reversed when SP are removed.

Massless geodesics in AdS 5 × Y ( p , q ) as a superintegrable system

A bstractA constant of motion of Carter type for a probe particle in the Y (p, q) EinsteinSasaki backgrounds is presented. This quantity is functionally independent with respect to the five known constants for these geometries. As the metric is five dimensional and the number of independent constants of motion is at least six, the geodesic equations turn out to be superintegrable. This result applies to the configuration of massless geodesic in AdS5 × Y (p, q) studied by Benvenuti and Kruczenski [86], which are matched to long BPS operators in the dual N = 1 supersymmetric gauge theory.

Effect of DHEA and metformin on corpus luteum in mice.

We evaluated the effect of hyperandrogenism in ovaries with functional and regressing corpora lutea (CL) and the action of metformin in preventing these possible alterations using a mouse model. To obtain a CL functional for 9+/-1 days, immature female mice of the BALB/c strain were injected i.p. with 10 IU/mouse of pregnant mares serum gonadotropin (PMSG). DHEA (60 mg/kg body weight s.c., 24 and 48 h prior to kill) decreased both serum progesterone (P) and estradiol (E(2)) levels and increased the activity of superoxide dismutase (SOD) from ovaries with functional CL (on day 5 after PMSG). It increased P and E(2) and the activities of SOD and catalase (CAT) and decreased lipoperoxidation of ovaries with regressing CL (on day 9 after PMSG). Treatment with DHEA did not affect the production of prostaglandin F(2alpha) (PGF(2alpha)) or PGE by ovaries with functional CL, whereas DHEA decreased PGF(2alpha) and increased PGE production by ovaries with regressing CL. Metformin (50 mg/kg body weight, orally) given together with DHEA restored E(2) levels from mice with ovaries with functional CL and serum P, PGF(2alpha) and PGE levels, and oxidative balance in mice with ovaries with regressing CL. Metformin alone was able to modulate serum P and E(2) levels, lipoperoxidation, SOD and CAT, and the 5,5-dimethyl-1-pyrroline N-oxide/(*)OH signal. These findings suggest that hyperandrogenism is able to induce or to rescue CL from luteolysis and metformin treatment is able to prevent these effects.

Effect of serum proteins on an exogenous pulmonary surfactant: ESR analysis of structural changes and their relation with surfactant activity

The study of the structural changes in surfactant microviscosity and bilayer organization would help to understand the mechanisms by which surfactant could be inactivated by serum components. The in vitro effects of human serum, albumin and gamma-globulin on dynamic and structural properties of surfactant suspensions and their heavy fractions were evaluated by electronic spin resonance and surface tension measurements. Our results showed that albumin and serum modified the aggregation state, transforming the active into inactive subtype, but only serum decreased the fluidity in the polar region and inactivated surfactant. In contrast, albumin and gamma-globulin generated a greater proportion of fluid-like disordered phase, without loss of surface activity. Statistical analysis showed that surface activity correlated with the fluidity in the polar area but not with that in the hydrophobic region. We concluded that one or more serum components different from albumin or gamma-globulin cause a structural change in the surfactant bilayer, increasing the rigidity in the polar area, which would be critical for proper physiological activity.

Synthesis, Characterization, and Catalytic Properties of Cationic Hydrogels Containing Copper(II) and Cobalt(II) Ions

Here, we report the synthesis and characterization of a hydrogel based on ethylene glycol diglycidyl ether (EGDE) and 1,8-diamino-3,6-dioxaoctane (DA). Chemically stable Co(II) and Cu(II) coordination complexes were prepared with this nonsoluble polyelectrolyte, poly(EGDE-DA), and studied by ss-NMR, FT-IR, thermogravimetry, and microscopy. Mesopores were found in all the samples, the thermal stability of the polymer matrix was highly affected by the presence of metal ions, and the (13)C CP-MAS spectrum for the Cu(II)-complex evidenced a significant increase in the reticulation degree by Cu(II) ions. The catalytic activity of these materials on H2O2 activation was studied by electron spin resonance (ESR). The Co(II)-poly(EGDE-DA)/H2O2 heterogeneous system produced O2, an anion superoxide (O2(•)¯), and a hydroxyl radical (OH(•)), which diffused into the solution at the time that a decrease in pH was detected. In the same way, the Cu(II)-poly(EGDE-DA)/H2O2 heterogeneous system produced O2 and OH(•). H2O2 activation by the poly(EGDE-DA) complexes with Co(II) and Cu(II) were applied on the decolorization of solutions of the azo-dye methyl orange (MO). In the presence of 63 mM H2O2, 87% of MO was removed in 10 min with Cu(II)-poly(EGDE-DA) and in 110 min with Co(II)-poly(EGDE-DA). In addition, the pharmaceutical product epinephrine was partially oxidized to adrenochrome by the O2(•)¯ released from the Co(II)-poly(EGDE-DA)/H2O2 heterogeneous system.

Oxidative Damage and Antioxidant Status in Diabetes Mellitus and Rheumatoid Arthritis: A Comparative Study

The present work compares and correlates antioxidant defenses and oxidative stress markers in patients with Diabetes Mellitus (DM) and in those with Rheumatoid Arthritis (RA) in order to find out if new evidences for a possible relationship between these pathologies can be found. Stress markers and antioxidant defenses were tested in blood sam- ples from RA, Type I and Type II DM patients. Erythrocytes (RBC) showed increased susceptibility to lipid peroxidation in both DM and RA, whereas basal oxidation was higher only in RA. Both pathologies showed elevated oxidized LDL concentration and decreased RBC membrane fluidity. In DM, plasma TRAP was decreased and showed an inverse corre- lation RBC oxidative damage. On the other hand, TRAP was normal in RA. In both pathologies, TRAP was not correlated with oxidized LDL. We can conclude that the peroxidative damage would occur through a complex mechanism, with dif- ferent factors involved in both illnesses. In this way, an association between these diseases could not be established.

Thin shells joining local cosmic string geometries

In this article we present a theoretical construction of spacetimes with a thin shell that joins two different local cosmic string geometries. We study two types of global manifolds, one representing spacetimes with a thin shell surrounding a cosmic string or an empty region with Minkowski metric, and the other corresponding to wormholes which are not symmetric across the throat located at the shell. We analyze the stability of the static configurations under perturbations preserving the cylindrical symmetry. For both types of geometries we find that the static configurations can be stable for suitable values of the parameters.