Publications (5)15.33 Total impact
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Article: Effect of serum proteins on an exogenous pulmonary surfactant: ESR analysis of structural changes and their relation with surfactant activity.
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ABSTRACT: 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.Respiratory Physiology & Neurobiology 06/2012; 183(1):48-57. · 2.24 Impact Factor -
Article: Influence of serum protein and albumin addition on the structure and activity of an exogenous pulmonary surfactant.
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ABSTRACT: 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.Respiratory Physiology & Neurobiology 03/2011; 175(3):316-21. · 2.24 Impact Factor -
Article: Synergistic encapsulation of the anti-HIV agent efavirenz within mixed poloxamine/poloxamer polymeric micelles.
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ABSTRACT: 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.Nanomedicine: nanotechnology, biology, and medicine 02/2011; 7(5):624-37. · 5.44 Impact Factor -
Article: Effect of DHEA and metformin on corpus luteum in mice.
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ABSTRACT: 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 mare's 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.Reproduction 07/2009; 138(3):571-9. · 2.58 Impact Factor -
Article: Structural insights into hydroxycoumarin-induced apoptosis in U-937 cells.
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ABSTRACT: In the present study, we sought to establish the effect of diverse structural-related hydroxycoumarins on the proliferation, cytotoxicity, and induction of apoptosis in promonocytic leukemic cells (U-937). The dihydroxylated coumarins, 7,8-dihydroxy-coumarin and esculetin, induced DNA fragmentation as well as characteristic morphological changes of programmed cell death in U-937 cells. With the aim to perform a structure-activity relationship study, the correlation between the physicochemical properties of the molecules and their pro-apoptotic activity was carried out. Results showed that the presence of two adjacent phenolic hydroxyl groups was the most important factor in terms of the SAR. The exposure of leukemic cells to 7,8-dihydroxy-coumarin evoked a phenoxyl radical generation that was detected by electron spin resonance spectroscopy. The present study suggests that reactive oxygen species generation plays a critical role in dihydroxycoumarin-induced apoptosis in U-937 cells. These findings further suggest that these compounds may have a potential therapeutic role in the treatment of hematological malignancies.Bioorganic & medicinal chemistry 04/2008; 16(5):2665-75. · 2.82 Impact Factor
