Confinement effect on the low temperature specific heat for ultrathin silicon nanowires: a first principles study.

This work studied the phonon confinement effects at the low temperature specific heat of Si nanowires from first principles using density functional perturbation theory. The nanowires were modeled in the [0 0 1] direction for three different diameters, with the largest cross section being approximately 10 Å. The results indicate the specific heat can be described at low temperatures using a third-grade polynomial of the form c v = λT + ßT 2 + γT3, where the coefficients of quadratic and cubic terms are almost nonexistent for small diameters. These terms begin to have relevance at larger diameters. Further analysis shows λ > ß > γ, which shows the phonon confinement (λ) and surface atoms (ß) become more important than the volumetric contribution (γ) for ultrathin nanowires at low temperatures.

Lithium effect on the electronic properties of porous silicon for energy storage applications: a DFT study.

Theoretical studies on the effect of Li on the electronic properties of porous silicon are still scarce; these studies could help us in the development of Li-ion batteries of this material which overcomes some limitations that bulk silicon has. In this work, the effect of interstitial and surface Li on the electronic properties of porous Si is studied using the first-principles density functional theory approach and the generalised gradient approximation. The pores are modeled by removing columns of atoms of an otherwise perfect Si crystal, dangling bonds of all surfaces are passivated with H atoms, and then Li is inserted on interstitial positions on the pore wall and compared with the replacement of H atoms with Li. The results show that the interstitial Li creates effects similar to n-type doping where the Fermi level is shifted towards the conduction band with band crossings of the said level thus acquiring metallic characteristics. The surface Li introduces trap-like states in the electronic band structures which increase as the number of Li atom increases with a tendency to become metallic. These results could be important for the application of porous Si nanostructures in Li-ion batteries technology.

[Cyclosporin A causes oxidative stress and mitochondrial dysfunction in renal tubular cells]. / La ciclosporina A origina estrés oxidativo y disfunción mitocondrial en células tubulares renales.

Reactive oxygen species (ROS) have been implicated in cyclosporin A (CsA) nephrotoxicity. As mitochondria are one of the main sources of ROS in cells, we evaluated the role of CsA in mitochondrial structure and function in LLC-PK1 cells. We incubated cells with CsA 1 microM for 24 hours and studies were performed with flow citometry and confocal microscopy. We studied mitochondrial NAD(P)H content, superoxide anion (O2.-) production (MitoSOX Red), oxidation of cardiolipin of inner mitochondrial membrane (NAO) and mitochondrial membrane potential (DIOC2(3)). Also we analyzed the intracellular ROS synthesis (H2DCF-DA) and reduced glutation (GSH) of cells. Our results showed that CsA decreased NAD(P)H and membrane potential, and increased O2.- in mitochondria. CsA also provoked oxidation of cardiolipin. Furthermore, CsA increased intracellular ROS production and decreased GSH content. These results suggest that CsA has crucial effects in mitochondria. CsA modified mitochondrial physiology through the decrease of antioxidant mitochondrial compounds as NAD(P)H and the dissipation of mitochondrial membrane potential and increase of oxidants as O2.-. Also, CsA alters lipidic structure of inner mitochondrial membrane through the oxidation of cardiolipin. These effects trigger a chain of events that favour intracellular synthesis of ROS and depletion of GSH that can compromise cellular viability. Nephrotoxic cellular effects of CsA can be explained, at least in part, through its influence on mitochondrial functionalism.

La ciclosporina A origina estrés oxidativo y disfunción mitocondrial en células tubulares renales / Cyclosporin a causes oxidative stress and mitochondrial dysfunction in renal tubular cells

Estudiamos el efecto de la ciclosporina A (CsA) sobre la estructura y función mitocondrial en células LLC-PK1. Las células se incubaron durante 24 horas con CsA 1 mM y se analizó la producción de anión superóxido, contenido de NAD(P)H, oxidación de cardiolipina y potencial de membrana mitocondrial; además se estudió la formación de radicales libres y el contenido de glutatión reducido intracelular. Nuestros resultados demuestran que la CsA provocó un aumento del anión superóxido mitocondrial de modo paralelo al descenso de NAD(P)H; además, se produjo oxidación de la cardiolipina de la membrana interna y un descenso del potencial de membrana mitocondrial. Finalmente, observamos un aumento de la producción de radicales libres intracelulares y un descenso del glutatión reducido. En conclusión, la CsA produce modificaciones importantes en la fisiología y estructura mitocondrial con aumento de la síntesis de especies reactivas de oxígeno y descenso de la capacidad antioxidante, hechos que podrían justificar la toxicidad celular de la droga

Reactive oxygen species (ROS) have been implicated in cyclosporin A (CsA) nephrotoxicity. As mitochondria are one of the main sources of ROS in cells, we evaluated the role of CsA in mitochondrial structure and function in LLC-PK1 cells. We incubated cells with CsA 1 mM for 24 hours and studies were performed by flow cytometry and confocal microscopy.We studied mitochondrial NAD(P)H content, superoxide anion (O2.-) production (MitoSOX Red), oxidation of cardiolipin of inner mitochondrial membrane (NAO) and mitochondrial membrane potential [DIOC2(3)]. We also analyzed the intracellular ROS synthesis (H2DCF-DA) and reduced glutation (GSH) of cells. Our results showed that CsA decreased NAD(P)H and membrane potential, and increased O2.- in mitochondria. CsA also provoked oxidation of cardiolipin. Furthermore, CsA increased intracellular ROS production and decreased GSH content. These results suggest that CsA has crucial effects in mitochondria. CsA modified mitochondrial physiology through the decrease of antioxidant mitochondrial compounds as NAD(P)H and the dissipation of mitochondrial membrane potential and increase of oxidants such O2.-. Also, CsA alters lipidic structure of inner mitochondrial membrane through the oxidation of cardiolipin. These effects trigger a chain of events that favour intracellular synthesis of ROS and depletion of GSH that can compromise cellular viability. Nephrotoxic cellular effects of CsA can be explained, at least in part, through its influence on mitochondrial functionalism

[All-trans retinoic acid induces apoptosis in human mesangial cells: involvement of stress activated p38 kinase]. / El ácido retinoico todo-trans induce apoptosis en células mesangiales humanas: implicación de la quinasa activada por estrés p38.

All-trans retinoic acid (AR-t) is used for treating acute promyelocytic leukemia and renal cell carcinoma and it also has therapeutic value in several animal models of renal disease. Among its renal targets, mesangial cells have been widely studied: they have both retinoic acid receptors (RAR) and retinoid X receptors (RXR) and the cell growth is inhibited when human mesangial cells are incubated with 1-10 microM AR-t. Although his effect has been related with the antiproliferative action of AR-t, there are no studies on the involvement of apoptosis in AR-t induced cell growth when higher concentrations of retinoid are used. Our studies show that 25 microM AR-t triggers mesangial cell apoptosis assessed by light and fluorescence microscopy (Giemsa stain and acridine orange stain, respectively), DNA electrophoresis, flow cytometry (annexin-V) and immunocytochemistry (TUNEL). AR-t induced apoptosis was not inhibited by preincubation with the RXR pan-antagonist HX531 nor with the RAR pan-antagonist AGN 193109, this suggesting RAR and RXIR are not involved in AR-t induced cell death. Previous results of our group showed that ERK (extracellular regulated kinase) and INK (c-Jun kinase), two members of the MAP (mitogen activated protein) kinase family, are involved in non apoptotic effects of AR-t on mesangial cells. Therefore we focussed on the stress activated p38 kinase, the third member of the MAPK family, to investigate its involvement in AR-t induced apoptosis. The results confirmed a role of p38 since: 1) preincubation with B5203589, a p38 inhibitor, inhibited ARA induced apoptosis; 2) incubation with AR-t induced p38 phosphorilation after few minutes and p38 remained phosphorilated for at least 8 hours and 3) AR-t induced p38 phosphorilation was inhibited by SB203589. These data suggest that AR-t might have toxic side effects on the kidney but also suggest that AR-t could be an useful inhibitor of pathological mesangial cell expansion.

El ácido retinoico todo-trans induce apoptosis en células mesangiales humanas: implicación de la quinasa activada por estrés p38 / All-trans retinoic acid induces apoptosis in human mesangial cells: involvement of stress activated p38 kinase

El ácido retinoico todo-trans (AR-t) se utiliza en clínica en el tratamiento de la leucemiapromielocítica aguda y el cáncer renal. También presenta efecto terapéutico endiversas formas de enfermedad renal experimental. Las células mesangiales son una delas dianas farmacológicas de AR-t mejor estudiadas: presentan receptores de ácido retinoico(RAR) y receptores X de retinoides (RXR) y el AR-t, a concentraciones entre 1 y 10µM, inhibe su crecimiento. Este efecto se ha relacionado con la acción antiproliferativadel AR-t, aunque no se ha estudiado la participación de mecanismos apoptóticos cuandose utilizan mayores concentraciones de AR-t. El presente trabajo demuestra que AR-t25 µM induce apoptosis de células mesangiales humanas en cultivo, caracterizada porestudios de microscopía óptica y de fluorescencia (tinciones de Giemsa y naranja deacridina, respectivamente), electroforesis del ADN fragmentado, citometría de flujo(anexina-V/ioduro de propidio) e inmunocitoquímica (TUNEL). Ni HX531 (pan-antagonistaRXR), ni AGN193109 (pan-antagonista RAR) redujeron el grado de muerte celularinducido por el AR-t, lo que sugiere un mecanismo independiente de receptores. Resultadosprevios de nuestro grupo indican que dos de los tres miembros de las quinasasactivadas por mitógenos (MAP), ERK (quinasa regulada por estímulos extracelulares) yJNK (quinasa de c-Jun), están implicados en efectos no apoptóticos del AR-t en célulasmesangiales. Nos centramos, pues, en el potencial pro-apoptótico del tercer miembro,la quinasa activada por estrés p38. Confirmamos su implicación en la apoptosis inducidapor el AR-t porque: 1) su inhibidor farmacológico, SB203580, previno dicha apoptosis2) El AR-t indujo en pocos minutos la fosforilación de p38, manteniéndose fosforiladadurante las 8 horas posteriores; y 3) dicha fosforilación se inhibió por preincubación conSB203580. Estos datos sugieren una posible toxicidad renal del AR-t, pero también suutilidad para controlar la proliferación patológica de células mesangiales

All-trans retinoic acid (AR-t) is used for treating acute promyelocytic leukemia andrenal cell carcinoma and it also has therapeutic value in several animal models of renaldisease. Among its renal targets, mesangial cells have been widely studied: they haveboth retinoic acid receptors (RAR) and retinoid X receptors (RXR) and the cell growthis inhibited when human mesangial cells are incubated with 1-10 µM AR-t. Althoughhis effect has been related with the antiproliferative action of AR-t, there are no studieson the involvement of apoptosis in AR-t induced cell growth when higher concentrationsof retinoid are used. Our studies show that 25 µM AR-t triggers mesangial cellapoptosis assessed by light and fluorescence microscopy (Giemsa stain and acridineorange stain, respectively), DNA electrophoresis, flow cytometry (annexin-V) andimmunocytochemistry (TUNEL). AR-t induced apoptosis was not inhibited by preincubationwith the RXR pan-antagonist HX531 nor with the RAR pan-antagonist AGN193109, this suggesting RAR and RXIR are not involved in AR-t induced cell death.Previous results of our group showed that ERK (extracellular regulated kinase) andJNK (c-Jun kinase), two members of the MAP (mitogen activated protein) kinasefamily, are involved in non apoptotic effects of AR-t on mesangial cells. Therefore wefocussed on the stress activated p38 kinase, the third member of the MAPK family, toinvestigate its involvement in AR-t induced apoptosis. The results confirmed a role ofp38 since: 1) preincubation with SB203589, a p38 inhibitor, inhibited ARA inducedapoptosis; 2) incubation with AR-t induced p38 phosphorilation after few minutesand p38 remained phosphorilated for at least 8 hours and 3) AR-t induced p38 phosphorilationwas inhibited by SB203589. These data suggest that AR-t migth have toxicside effects on the kidney but also suggest that AR-t could be an useful inhibitor of pathologicalmesangial cell expansion

Implications of upper respiratory tract infections and drugs in the clinical spectrum of Henoch-Schönlein purpura in children.

OBJECTIVE: To assess whether children with Henoch-Schonlein purpura (HSP) who had an upper respiratory tract infection (URTI) or received medication prior to the onset of the disease exhibited a different clinical spectrum of features and outcome from children without such a history. METHODS: Retrospective study of children (< or = 14 years old) with HSP diagnosed from 1980 through December 2001 at the single hospital for the Lugo region (Northwest Spain). Children with primary cutaneous vasculitis were classified as having HSP according to currently used criteria. Drugs or URTI were considered precipitating events if any new medication was taken or an URTI had occurred within a week prior to the onset of the vasculitis. A comparative analysis of clinical and laboratory features according to the presence or absence of URTI and drugs was conducted. RESULTS: Eighty-six children fulfilled the classification criteria for HSP. Eight of them were excluded from this analysis due to insufficient follow-up (less than 1 year post-diagnosis). An URTI and a history of drugs were reported to occur in 32/78 (41%) and 23/78 (30%) children respectively. No differences in the age at the onset of the disease, gender and seasonal incidence between children with or without URTI were observed. However, 23/32 (72%) children with URTI had hematuria with or without proteinuria, compared with only 18/46 (39%) children without history of URTI (p = 0.004). This higher incidence of renal manifestations in HSP with URTI was not associated with more severe nephritis or with a significantly higher frequency of renal sequelae or relapses of the disease. No statistically significant differences between children with or without a history of drugs were observed. CONCLUSION: Although in unselected children with HSP a history of URTI seems to be associated with a higher incidence of nephritis, it does not influence the outcome of the disease.

Generation and mid-IR measurement of a gas-phase to predict security parameters of aviation jet fuel.

The worldwide use of kerosene as aviation jet fuel makes its safety considerations of most importance not only for aircraft security but for the workers' health (chronic and/or acute exposure). As most kerosene risks come from its vapours, this work focuses on predicting seven characteristics (flash point, freezing point, % of aromatics and four distillation points) which assess its potential hazards. Two experimental devices were implemented in order to, first, generate a kerosene vapour phase and, then, to measure its mid-IR spectrum. All the working conditions required to generate the gas phase were optimised either in a univariate or a multivariate (SIMPLEX) approach. Next, multivariate prediction models were deployed using partial least squares regression and it was found that both the average prediction errors and precision parameters were satisfactory, almost always well below the reference figures.

Metabotropic glutamate receptor involvement in phosphoinositide hydrolysis stimulation by an endogenous Na(+), K(+)-ATPase inhibitor and ouabain in neonatal rat brain.

The mechanism of action of an endogenous Na(+), K(+)-ATPase inhibitor, termed endobain E, on phosphoinositide hydrolysis was studied in neonatal rat brain cortex and compared with that of ouabain. Lack of additivity for endobain E and glutamate paired stimulation on inositol phosphates accumulation suggested that they share at least a common step on inositol phosphate metabolism, as previously advanced for ouabain. In addition, Cd(2+) sensitivity of endobain E and ouabain effects strengthened the involvement of glutamate receptors. The participation of ionotropic glutamate receptors on endobain E- and ouabain-induced phosphoinositide hydrolysis seems untenable, since antagonists dizocilpine and CNQX proved unable to inhibit these effects. However, the endobain E effect was blocked by 2 x 10 (-4) M L-AP3 (an antagonist for group I mGluRs) when at least a 15-min preincubation protocol was employed. Maximal inhibition of endobain E effect (42%) occurred when L-AP3 preincubation was extended to 60 min, as already shown with glutamate, but only a trend to decrease was recorded with ouabain. At variance, the ouabain effect was reduced to 50% employing 5 x 10 (-4) M MCPG (a competitive antagonist for group I mGluRs), whereas no blockade was observed with endobain E or glutamate. In addition, MPEP (a selective mGluR5 antagonist) partially reduced ouabain, endobain E and glutamate responses and the selective mGluR1 antagonist LY367385 showed no activity at all. To sum up, the present findings support the involvement of mGluR5 in both endobain E and ouabain phosphoinositide hydrolysis stimulation in neonatal rat brain, in spite of dissimilar response to tested antagonists.

HLA-DRB1*01 association with Henoch-Schönlein purpura in patients from northwest Spain.

OBJECTIVE: To examine the HLA-DRB1 phenotypes of patients with Henoch-Schönlein purpura (HSP) and determine if associations exist with disease susceptibility, clinical heterogeneity, or severe systemic complications. METHODS: A retrospective study was performed on an unselected population of patients from Northwest Spain with HSP classified according to proposed criteria. Patients were included in this study if they had at least one year of followup. Fifty Caucasian patients (25 women), 11 of them older than 20 years, were studied. Patients and ethnically matched controls were HLA-DRB1 genotyped from DNA using molecular based methods. RESULTS: During the course of the disease, renal manifestations, especially hematuria, and severe gastrointestinal (GI) manifestations (bowel angina or GI bleeding) were observed in more than 60% of the patients. Twenty percent of patients had persistent renal involvement (renal sequelae). Patients with HSP had a significantly higher frequency of the HLA-DRB1*01 phenotype compared to matched controls. The HLA-DRB1*07 phenotype was also significantly reduced compared with controls. Patients with severe GI manifestations or with persistent renal involvement did not exhibit any specific HLA-DRB1 association other than the underlying association with HLA-DRB1*01. CONCLUSION: HSP in a population from Northwest Spain is significantly associated with HLA-DRB1*01.

Polymorphism at codon 469 of the intercellular adhesion molecule-1 locus is associated with protection against severe gastrointestinal complications in Henoch-Schönlein purpura.

OBJECTIVE: Henoch-Schonlein purpura (HSP) is a small sized vasculitis affecting mainly children. Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms have recently been implicated in the susceptibility to some vasculitides. To further investigate the clinical implication of ICAM-1 polymorphisms in HSP, we examined their potential association and influence in the development of severe complications in an unselected series of patients with HSP. METHODS: Fifty-two patients, of which 41 were children, were diagnosed with HSP using classification criteria of Michel, et al at the Hospital Xeral-Calde (Lugo, Spain); 129 ethnically matched controls were included. Patients had at least one year of followup. Patients and controls were genotyped by allelic oligonucleotide techniques for ICAM-I polymorphism at codon 241 and 469. RESULTS: The frequency distribution of the alleles and genotypes for each ICAM-1 polymorphism did not show significant differences between HSP patients and controls. Also, no differences between patients with or without renal manifestations were found. However, the frequency of the codon 469 K/E genotype was significantly decreased in patients without severe gastrointestinal manifestations compared to those with them (22.29 vs 65%, OR 0.1, p = 0.02, after correction for age, sex, and disease duration). None of the 11 adults exhibited the R/G genotype at codon 241 compared with 7 of 41 children (OR 0.0, 95% CI 0.0-2.9, p = 0.14). Patients with the R/G genotype were associated with low incidence of renal manifestations and none developed permanent renal involvement (renal sequelae); however, this finding did not achieve statistical significance. CONCLUSION: ICAM-1 polymorphisms alone are not associated with development of HSP, but patients not carrying the codon 469 K/E genotype are at decreased risk of developing severe gastrointestinal complications. The R/G polymorphism at codon 241 may reduce the risk of renal sequelae in the development of HSP in adulthood.

An endogenous Na+, K+-ATPase inhibitor enhances phosphoinositide hydrolysis in neonatal but not in adult rat brain cortex.

The effect of an endogenous Na+, K+-ATPase inhibitor, termed endobain E, on phosphoinositide hydrolysis was studied in rat brain cortical prisms and compared with that of ouabain. As already shown for ouabain, a transient effect was obtained with endobain E; maximal accumulation of inositol phosphates induced by endobain E was 604 +/- 138% and 186 +/- 48% of basal values in neonatal and adult rats, respectively. The concentration-response plot for the interaction between endobain E and phosphoinositide turnover differed from that of ouabain, thus suggesting the involvement of distinct mechanisms. In the presence of endobain E plus ouabain at saturating concentrations, no additive effect was recorded, suggesting that both substances share at least a common step in their activation mechanism of inositol phosphates metabolism or that they enhance phosphatidylinositol 4,5-biphosphate breakdown from the same membrane precursor pool, until its exhaustion. Experiments with benzamil, a potent blocker of Na+/Ca2+ exchanger, showed that it partially and dose-dependently inhibited endobain E effect. These results indicate that the endogenous Na+, K+-ATPase inhibitor endobain E, like ouabain, is able to stimulate phosphoinositide turnover transiently during postnatal brain development.

Endogenous modulators of brain Na+,K(+)-ATPase at early postnatal stages of rat development.

The presence of endogenous modulators (peaks I and II) of synaptosomal Na+, K(+)-ATPase activity from adult rat cerebral cortex was previously suggested. In this study, the presence of such modulators at different postnatal stages of rat development was examined and their effect was tested on Na+, K(+)-ATPase activity. Synaptosomal membrane Na+, K(+)-ATPase activity was enhanced 20-30% by peak I and inhibited 70-75% by peak II obtained from 4-, 10-, 20- and 35-40-day-old rats. A fraction purified from peak II by anionic exchange HPLC (termed II-E) highly inhibits enzyme activity and behaves as a ouabain-like factor. Inhibitory activity of a 4-day-old II-E fraction proved higher than the corresponding fraction obtained from adult rats. Since expression of cerebral Na+, K(+)-ATPase has been shown to increase 10-fold during development whereas peak II concentration was observed to remain constant, and given the higher potency of purified neonatal II-E fraction, the effect of the latter may be greater at early postnatal stages of development than during adult life. It is suggested that the II-E fraction, which contains an ouabain-like factor, may play a role in neuronal development.

Bone marrow transplantation in chronic granulomatous disease.

UNLABELLED: We present a 5-year-old boy with a severe form of X-linked chronic granulomatous disease and hypersensitivity to sulphamides preventing prophylaxis with trimethoprim-sulphomethoxazole. Bone marrow transplantation was performed after preconditioning with busulphan and cyclophosphamide. The immediate post-transplant period was without complications. Complete chimerism was demonstrated and post-transplant oxidative metabolism was normal. The patient is asymptomatic 30 months after the graft. CONCLUSION: Bone marrow transplantation in cases of chronic granulomatous disease is controversial, although it could be useful in selected very severe cases in which prophylactic therapy is problematic.