Antioxidant, anti-inflammatory and neuroprotective actions of resveratrol after experimental nervous system insults. Special focus on the molecular mechanisms involved.

After different types of acute central nervous system insults, including stroke, subarachnoid haemorrhage and traumatic brain and spinal cord injuries, secondary damage plays a central role in the induction of cell death, neurodegeneration and functional deficits. Interestingly, secondary cell death presents an attractive target for clinical intervention because the temporal lag between injury and cell loss provides a potential window for effective treatment. While primary injuries are the direct result of the precipitating insult, secondary damage involves the activation of pathological cascades through which endogenous factors can exacerbate initial tissue damage. Secondary processes, usually interactive and overlapping, include oxidative stress, neuroinflammation and dysregulation of autophagy, ultimately leading to cell death. Resveratrol, a natural stilbene present at relatively high concentrations in grape skin and red wine, exerts a wide range of beneficial health effects. Within the central nervous system, in addition to its inherent free radical scavenging role, resveratrol increases endogenous cellular antioxidant defences thus modulating multiple synergistic pathways responsible for its antioxidant, anti-inflammatory and anti-apoptotic properties. During the last years, a growing body of in vitro and in vivo evidence has been built, indicating that resveratrol can induce a neuroprotective state and attenuate functional deficits when administered acutely after an experimental injury to the central nervous system. In this review, we summarize the most recent findings on the molecular pathways involved in the neuroprotective effects of this multi target polyphenol, and discuss its neuroprotective potential after brain or spinal cord injuries.

Intrathecal Administration of an Anti-nociceptive Non-CpG Oligodeoxynucleotide Reduces Glial Activation and Central Sensitization.

Inflammatory pain associates with spinal glial activation and central sensitization. Systemic administration of IMT504, a non-CpG oligodeoxynucleotide originally designed as an immunomodulator, exerts remarkable anti-allodynic effects in rats with complete Freund´s adjuvant (CFA)-induced hindpaw inflammation. However, the anti-nociceptive mechanisms of IMT504 remain unknown. Here we evaluated whether IMT504 blocks inflammatory pain-like behavior by modulation of spinal glia and central sensitization. The study was performed in Sprague Dawley rats with intraplantar CFA, and a single lumbosacral intrathecal (i.t.) administration of IMT504 or vehicle was chosen to address if changes in glial activation and spinal sensitization relate to the pain-like behavior reducing effects of the ODN. Naïve rats were also included. Von Frey and Randall-Selitto tests, respectively, exposed significant reductions in allodynia and mechanical hypersensitivity, lasting at least 24 h after i.t. IMT504. Analysis of electromyographic responses to electrical stimulation of C fibers showed progressive reductions in wind-up responses. Accordingly, IMT504 significantly downregulated spinal glial activation, as shown by reductions in the protein expression of glial fibrillary acidic protein, CD11b/c, Toll-like receptor 4 (TLR4) and the phosphorylated p65 subunit of NFκB, evaluated by immunohistochemistry and western blot. In vitro experiments using early post-natal cortical glial cultures provided further support to in vivo data and demonstrated IMT504 internalization into microglia and astrocytes. Altogether, our study provides new evidence on the central mechanisms of anti-nociception by IMT504 upon intrathecal application, and further supports its value as a novel anti-inflammatory ODN with actions upon glial cells and the TLR4/NFκB pathway. Intrathecal administration of the non-CpG ODN IMT504 fully blocks CFA-induced mechanical allodynia and hypersensitivity, in association with reduced spinal sensitization. Administration of the ODN also results in downregulated gliosis and reduced TLR4-NF-κB pathway activation. IMT504 uptake into astrocytes and microglia support the concept of direct modulation of CFA-induced glial activation.

Resveratrol exerts anti-oxidant and anti-inflammatory actions and prevents oxaliplatin-induced mechanical and thermal allodynia.

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a frequent and devastating side effect of cancer therapy. No preventive strategies are currently available. We investigated the use of resveratrol (RESV) in the prevention of CIPNP and evaluated key components of the antioxidant defense system and neuroinflammatory factors as possible mediators contributing to RESV actions. Male rats were injected with oxaliplatin (OXA) and received daily oral RESV. Paw mechanical and thermal allodynia, oxidative stress, antioxidant, pro-inflammatory and neuronal injury/activation markers were evaluated in the sciatic nerve (SN), lumbar dorsal root ganglia (DRG) and spinal cord (SC). OXA-injected animals developed mechanical and thermal allodynia, while those receiving OXA + RESV showed patterns of response similar to control animals. Higher TBARS levels and lower GSH/GSSG ratios were observed in the SN of animals receiving OXA. The mRNA levels of the transcription factor NFκB and the pro-inflammatory cytokine TNFα were found to be upregulated both in lumbar DRG and SC. In addition, the antioxidant enzymes NQO-1 and HO-1 and the neuronal injury marker ATF3 showed increased levels of expression in lumbar DRG. In the dorsal SC the neuronal activation marker c-fos and the transcription factor Nrf2, main regulator of antioxidant defenses, were found to be upregulated. RESV early and sustained administration prevented NFκB, TNFα, ATF3 and c-fos upregulation, while increasing the expression of Nrf2, NQO-1, HO-1 and the redox-sensitive deacetylase SIRT1. RESV treatment was also able to restore TBARS levels and GSH/GSSG ratio. Thus, RESV administration resulted in the upregulation of antioxidant mediators, suppression of pro-inflammatory parameters and prevention of OXA-induced mechanical and thermal allodynia.

Small RNAs from a Big Genome: The piRNA Pathway and Transposable Elements in the Salamander Species Desmognathus fuscus.

Most of the largest vertebrate genomes are found in salamanders, a clade of amphibians that includes 686 species. Salamander genomes range in size from 14 to 120 Gb, reflecting the accumulation of large numbers of transposable element (TE) sequences from all three TE classes. Although DNA loss rates are slow in salamanders relative to other vertebrates, high levels of TE insertion are also likely required to explain such high TE loads. Across the Tree of Life, novel TE insertions are suppressed by several pathways involving small RNA molecules. In most known animals, TE activity in the germline is primarily regulated by the Piwi-interacting RNA (piRNA) pathway. In this study, we test the hypothesis that salamanders' unusually high TE loads reflect the loss of the ancestral piRNA-mediated TE-silencing machinery. We characterized the small RNA pool in the female and male adult gonads, testing for the presence of small RNA molecules that bear the characteristics of TE-targeting piRNAs. We also analyzed the amino acid sequences of piRNA pathway proteins from salamanders and other vertebrates, testing whether the overall patterns of sequence divergence are consistent with conserved pathway function across the vertebrate clade. Our results do not support the hypothesis of piRNA pathway loss; instead, they suggest that the piRNA pathway is expressed in salamanders. Given these results, we propose hypotheses to explain how the extraordinary TE loads in salamander genomes could have accumulated, despite the expression of TE-silencing machinery.

Vacunación de gripe en niños con diagnóstico de diabetes mellitus tipo 1 en un área suburbana de Madrid / Influenza vaccination in children with type I mellitus diabetes in a suburban area in Madrid

Objetivo: determinar la tasa de vacunación frente a la gripe en el grupo de pacientes con diabetes mellitus (DM) tipo 1 en seguimiento en nuestro centro. Material y métodos: en los pacientes con diagnóstico de DM tipo 1 se realiza un estudio transversal descriptivo analizando la tasa de vacunación frente a la gripe. Resultados: se incluyen 37 pacientes (varones/mujeres: 1,6/1). La edad media es 9,7 años y el tiempo de evolución de la enfermedad tres años. El 51,3% ha sido vacunado contra la gripe en 2010, frente al 80% en 2009. Los niños con un tiempo de evolución entre tres y seis años son los menos vacunados (22% de los vacunados), frente al resto (56%). Conclusiones: la cobertura vacunal frente al virus de la gripe es escasa en nuestro medio, aunque superior a la referida para el territorio español (36,7%). Es necesaria la recomendación de la vacunación antigripal a pacientes diabéticos (AU)

Objective: To determine the rate of flu vaccination in the group of patients followed in our hospital because of type 1 diabetes. Methods: A descriptive study is conducted in patients with type 1 diabetes, analyzing the rate of vaccination against influenza. Results: 37 patients were included (male/female: 1.6/1). The mean age was 9.7 years and the mean duration of disease 3 years. 51.3% patients have been vaccinated against influenza in 2010 versus 64.86% in 2009. Children with a disease evolution between 3 and 6 years are the least vaccinated (22% vaccinated), compared to the rest (56%). Conclusions: Vaccination coverage against influenza virus is low in our area, although higher than the referred in Spanish population (36.7%). Recommendation on influenza vaccination is required in diabetic patients (AU)

Bone marrow stromal cells attenuate injury-induced changes in galanin, NPY and NPY Y1-receptor expression after a sciatic nerve constriction.

Single ligature nerve constriction (SLNC) of the rat sciatic nerve triggers neuropathic pain-related behaviors and induces changes in neuropeptide expression in primary afferent neurons. Bone marrow stromal cells (MSCs) injected into the lumbar 4 (L4) dorsal root ganglia (DRGs) of animals subjected to a sciatic nerve SLNC selectively migrate to the other ipsilateral lumbar DRGs (L3, L5 and L6) and prevent mechanical and thermal allodynia. In this study, we have evaluated the effect of MSC administration on the expression of the neuropeptides galanin and NPY, as well as the NPY Y(1)-receptor (Y(1)R) in DRG neurons. Animals were subjected to a sciatic nerve SLNC either alone or followed by the administration of MSCs, phosphate-buffered saline (PBS) or bone marrow non-adherent mononuclear cells (BNMCs), directly into the ipsilateral L4 DRG. Seven days after injury, the ipsilateral and contralateral L4-5 DRGs were dissected out and processed for standard immunohistochemistry, using specific antibodies. As previously reported, SLNC induced an ipsilateral increase in the number of galanin and NPY immunoreactive neurons and a decrease in Y(1)R-positive DRG neurons. The intraganglionic injection of PBS or BNMCs did not modify this pattern of expression. In contrast, MSC administration partially prevented the injury-induced changes in galanin, NPY and Y(1)R expression. The large number of Y(1)R-immunoreactive neurons together with high levels of NPY expression in animals injected with MSCs could explain, at least in part, the analgesic effects exerted by these cells. Our results support MSC participation in the modulation of neuropathic pain and give insight into one of the possible mechanisms involved.

[The HOMA and QUICKI indexes, and insulin and C-peptide levels in healthy children. Cut off points to identify metabolic syndrome in healthy children]. / Indice HOMA y QUICKI, insulina y péptido C en niños sanos. Puntos de corte de riesgo cardiovascular.

OBJECTIVE: The aim of this study was to establish the reference values of the Homeostasis Model Assessment (HOMA) and Quantitative Insulin Sensitivity Check (QUICKI) indexes, as well as those of insulin and C-peptide levels in healthy children and adolescents with a view to determining reference percentiles to detect those at cardiovascular risk. MATERIAL AND METHODS: A total of 372 children boys and girls of different ages and at distinct pubertal stages with normal body mass index participated in the study. Fasting glucose, insulin and C-peptide values were measured by chemiluminescence and the HOMA and QUICKI indexes were calculated. RESULTS: Fasting glucose levels were normal in all children. The mean values obtained for each variable were (mean (SD)): fasting glucose 87(7.75) mg/dL, insulin 7.74 (5.35) microU/mL, C-peptide: 1.76 (0.79) ng/mL, HOMA index 1.72 (1.27) and QUICKI index 0.72 (0.29). All the variables progressively increased with age, with statistically significant differences between prepubertal and pubertal children. The QUICKI index showed an inverse relationship. In addition, significant differences were found between sexes. The 90th percentile for all the variables was as follows: insulin 15.05 microU/mL, C-peptide: 2.85 ng/mL, HOMA index 3.43 and QUICKI index 1.10. CONCLUSIONS: Values of fasting glucose, insulin, C-peptide and the HOMA index significantly increased with age and pubertal stage, while the QUICKI index decreased. We defined the 90th percentile for all the parameters studied as the cut-off point to identify children at cardiovascular risk in our population.

Índice HOMA y QUICKI, insulina y péptido C en niños sanos. Puntos de corte de riesgo cardiovascular / The HOMA and QUICKI indexes, and insulin and C-peptide levels in healthy children. Cut off points to identify metabolic syndrome in healthy children

Objetivo: El objetivo de este trabajo ha sido establecer los valores de referencia de los índices Homeostasis Model Assessment (HOMA) y Quantitative Insulin Sensitivity Check Index (QUICKI), insulina y péptido C en ayunas en niños sanos, y con ello obtener percentiles de referencia a partir de los cuales establecer un punto de corte para valorar el riesgo cardiovascular en nuestra población infantil. Material y métodos: En este estudio participan 372 niños de ambos sexos y diferente estadio puberal con un índice de masa corporal (IMC) normal. Se determinan los valores de glucemia, insulina y péptido C (mediante quimioluminiscencia), y se calculan los índice HOMA y QUICKI. Resultados: Todos los niños presentan niveles de glucemia normales (media [DE]): 87 (7,75) mg/dl. Los valores medios obtenidos para cada variable son: insulina 7,74 (5,35) μU/ml, péptido C: 1,76 (0,79) ng/ml, índice HOMA: 1,72 (1,27), e índice QUICKI 0,72 (0,29). De forma global se objetiva un aumento progresivo de los valores de glucosa, insulina, péptido C y el índice HOMA en relación con la edad, existiendo diferencias estadísticamente significativas entre estadios prepuberales y puberales para ambos sexos, siguiendo el índice QUICKI un patrón inverso. Así mismo existen diferencias significativas entre sexos para todas las variables e índices estudiados. Los valores obtenidos para el percentil P90 para cada variable e índice de forma global son: insulina 15,05 μU/ml, péptido C: 2,85 ng/ml, índice HOMA 3,43 e índice QUICKI: 1,10. Conclusiones: Los valores de glucemia, insulina, péptido C y el índice HOMA aumentan con la edad y el estadio puberal de forma significativa. El índice QUICKI por el contrario disminuye. Establecemos el percentil P90 de estas variables que nos servirá como punto de referencia para valorar el riesgo cardiovascular en nuestra población

Objective: The aim of this study was to establish the reference values of the Homeostasis Model Assessment (HOMA) and Quantitative Insulin Sensitivity Check (QUICKI) indexes, as well as those of insulin and C-peptide levels in healthy children and adolescents with a view to determining reference percentiles to detect those at cardiovascular risk. Material and methods: A total of 372 children boys and girls of different ages and at distinct pubertal stages with normal body mass index participated in the study. Fasting glucose, insulin and C-peptide values were measured by chemiluminescence and the HOMA and QUICKI indexes were calculated. Results: Fasting glucose levels were normal in all children. The mean values obtained for each variable were (mean (SD)): fasting glucose 87(7.75) mg/dL, insulin 7.74 (5.35) mcU/mL, C-peptide: 1.76 (0.79) ng/mL, HOMA index 1.72 (1.27) and QUICKI index 0.72 (0.29). All the variables progressively increased with age, with statistically significant differences between prepubertal and pubertal children. The QUICKI index showed an inverse relationship. In addition, significant differences were found between sexes. The 90th percentile for all the variables was as follows: insulin 15.05 mcU/mL, C-peptide: 2.85 ng/mL, HOMA index 3.43 and QUICKI index 1.10. Conclusions: Values of fasting glucose, insulin, C-peptide and the HOMA index significantly increased with age and pubertal stage, while the QUICKI index decreased. We defined the 90th percentile for all the parameters studied as the cut-off point to identify children at cardiovascular risk in our population

Presence of alpha-globin mRNA and migration of bone marrow cells after sciatic nerve injury suggests their participation in the degeneration/regeneration process.

We have previously reported that in the distal stump of ligated sciatic nerves, there is a change in the distribution of myelin basic protein (MBP) and P0 protein immunoreactivities. These results agreed with the studies of myelin isolated from the distal stump of animals submitted to ligation of the sciatic nerve, showing a gradual increase in a 14 kDa band with an electrophoretic mobility similar to that of an MBP isoform, among other changes. This band, which was resolved into two bands of 14 and 15 kDa using a 16% gel, was found to contain a mixture of MBP fragments and peptides with great homology with alpha- and beta-globins. In agreement with these results, we have demonstrated that the mRNA of alpha-globin is present in the proximal and distal stumps of the ligated nerve. It is also detected at very low levels in Schwann cells isolated from normal nerves. These results could be due to the presence of alpha- and/or beta-globin arising from immature cells of the erythroid series. Also, they could be present in macrophages, which spontaneously migrate to the injured nerve to promote the degradation of myelin proteins. Cells isolated from normal adult rat bone marrow which were injected intraortically were found to migrate to the injured area. These cells could contribute to the remyelination of the damaged area participating in the removal of myelin debris, through their transdifferentiation into Schwann cells or through their fusion with preexisting Schwann cells in the distal stump of the injured sciatic nerve.

Diagnóstico por imagen de la enfermedad de Kienböck / Methods of imaging in Kienböck´s disease

Se revisa la aportación de los diferentes métodos de diagnósticopor imagen en la enfermedad de Kienböck, siendoel TAC y la RM las técnicas de elección

We review the contribution of different methods of imagingin Kienböck disease diagnostic, CT and MRI areprincipal techniques

Masa paracardial derecha y mediastínica anteroinferior de densidad heterogénea, como hallazgo / Heterogeneous paracardiac/mediastinal mass as a casual finding

Se presenta un caso de masa paracardial derecha, mediastínica anteroinferior, de densidad heterogénea con contenido aéreo, como hallazgo en estudio radiológico convencional de rutina en examen preoperatorio para herniorrafia inguinal. Se analizan las características de la masa en radiología convencional y TAC, estableciéndose el diagnóstico diferencial entre las masas retroesternales

An heterogeneous mass localized in the anteroinferior mediastinum (paracardiac) was identified at a X-ray examination, as part of a routine pre-operative (inguinal herniorraphy) evaluation. X-ray and CT findings are analyzed and several differential diagnosis are proposed

Masa mediastínica anterosuperior en anciano varón afectado por multipatología heterogénea de carácter benigno / Superior mediastinal mass in an elderly patient whith multiple and heterogeneous pathology

Se presenta el caso de un paciente anciano con múltiplepatología benigna y heterogénea que consulta por pérdidade peso superior a 10 Kg en un año sin ninguna sintomatologíaajena a sus antecedentes, detectándose en el estudiocomplementario una masa cérvico torácica que invade elmediastino superior. Se analizan las características de la masaen radiología convencional, TAC, ecografía y gammagrafía,estableciéndose el diagnóstico diferencial entre las masasdel mediastino superior

We report a case of an elderly patient with multiple benignand heterogeneous pathology that consults for lossweight superior to 10 Kg in one year without any othersymptomatology.A mass that invaded superior mediastinumwas detected in the X-ray chest.The characteristics of themass and the complementary studies are analyzed

The S-phase fraction of the aneuploid cell subpopulation is the biologically relevant one in aneuploid breast cancers.

BACKGROUND: In the case of DNA-aneuploid tumors there are no clear guidelines as to which S-phase fraction is the more relevant one: that corresponding to either the diploid or the aneuploid population, or rather an average of both. MATERIALS AND METHODS: We studied 280 breast cancer specimens from previously untreated patients. Histologically, 231 were ductal infiltrating carcinomas, 30 lobular infiltrating carcinomas and 19 corresponded to other, less frequent varieties. Postsurgically, 164 cases (58.6%) were classified as T1, 87 (31.1%) as T2 and 7 as T3. The remaining 22 cases were multifocal, diffuse tumors. Flow cytometry was performed on fresh tumor tissue, and immunohistochemistry for hormone receptors, Ki67, c-erb-B2 and p53 on paraffin-embedded material. RESULTS: In diploid tumors, a high S-phase (above the 75th percentile) correlated significantly with Ki67 expression > or =20% (p<0.0001). In aneuploid tumors, however, this was only the case for the aneuploid fraction of tumor cells (p< 0.0001). A high S-phase of diploid tumors correlated directly and significantly with a high histologic grade (p=0.04), a high nuclear grade (p=0.01), tumor size (p=0.0008), and inversely with estrogen (p<0.0001) and progesterone (p<0.0001) receptor expression. In aneuploid tumors, the aneuploid tumor fraction showed a direct and significant correlation with a high histologic grade (p=0.005), a high nuclear grade (p=0.001), mutant p53 expression (p=0.0009), and inversely with estrogen (p<0.0001) and progesterone (p=0.0001) receptor expression. A high S-phase of the diploid cell fraction of aneuploid tumors, on the other hand, just showed an inverse correlation with high nuclear grade of the tumors (p=0.02), and none whatsoever with all other tested parameters.

Prevención y tratamiento de la toxicidad torácica / No disponible

No disponible

Hiperclaridad pulmonar: revisión y comentario, a propósito de un caso / Lung hiperlucency: case report and review of the literature

El enfisema bulloso es una forma progresiva de enfisemaque aparece en varones jóvenes. Se realiza una revisión de lasdiferentes causas que se plantean en el diagnostico diferencialde hiperclaridad pulmonar y la aportación de la TAC de alta resoluciónen el estudio radiológico de esta entidad

Bullous emphysema is a progressive variant of emphysemaoccuring in young men. We present a case-report and reviewthe differential diagnosis of lung hyperlucency and the role ofhigh-resolution computed tomography (HRCT) in the radiologicwork-up of this entity