Magnetic resonance arthrography accuracy in the detection of labral tears in young patients with chronic unstable shoulder: correlation with arthroscopy.

The aim of this study is to determine the diagnostic performance of Magnetic Resonance Arthrography (MRA) in evaluating lesions of the glenoid labrum, in young active patients with chronic unstable shoulder, compared to shoulder arthroscopy. We retrospectively considered 65 MRA examinations, performed between December 2011 and January 2018. Among them, thirty-five patients (31 men, 4 women; mean age, 27.3 years; range, 16-53 years; 4 patients with a previous arthroscopy of the same shoulder) underwent shoulder arthroscopy after MRA. Arthroscopic reports were collected and analyzed for the correlation with MRA results.

Bone texture analysis using CT-simulation scans to individuate risk parameters for radiation-induced insufficiency fractures.

This study deals with the role of texture analysis as a predictive factor of radiation-induced insufficiency fractures in patients undergoing pelvic radiation. INTRODUCTION: This study aims to assess the texture analysis (TA) of computed tomography (CT) simulation scans as a predictive factor of insufficiency fractures (IFs) in patients with pelvic malignancies undergoing radiation therapy (RT). METHODS: We performed an analysis of patients undergoing pelvic RT from January 2010 to December 2014, 24 of whom had developed pelvic bone IFs. We analyzed CT-simulation images using ImageJ macro software and selected two regions of interest (ROIs), which are L5 body and the femoral head. TA parameters included mean (m), standard deviation (SD), skewness (sk), kurtosis (k), entropy (e), and uniformity (u). The IFs patients were compared (1:2 ratio) with controlled patients who had not developed IFs and matched for sex, age, menopausal status, type of tumor, use of chemotherapy, and RT dose. A reliability test of intra- and inter-reader ROI TA reproducibility with the intra-class correlation coefficient (ICC) was performed. Univariate and multivariate analyses (logistic regression) were applied for TA parameters observed both in the IFs and the controlled groups. RESULTS: Inter- and intra-reader ROI TA was highly reproducible (ICC > 0.90). Significant TA parameters on paired t test included L5 m (p = 0.001), SD (p = 0.002), k (p = 0.006), e (p = 0.004), and u (p = 0.015) and femoral head m (p < 0.001) and SD (p = 0.001), whereas on logistic regression analysis, L5 e (p = 0.003) and u (p = 0.010) and femoral head m (p = 0.027), SD (p = 0.015), and sex (p = 0.044). CONCLUSIONS: In our experience, bone CT TA could be correlated to the risk of radiation-induced IFs. Studies on a large patient series and methodological refinements are warranted.

Sperm with fibrous sheath dysplasia and anomalies in head-neck junction: focus on centriole and centrin 1.

Spermatozoa with a rare combination of two monomorphic sperm defects, dysplasia of the fibrous sheath (DFS) and alterations in head-mid-piece junction were analysed. The main focus was to explore the status of the centriole, a key organisation during fertilisation, using the centrin 1, a calcium-binding protein linked to this structure. The sperm quality was examined by light, scanning and transmission electron microscopy (SEM, TEM); immunocytochemistry was performed for tubulin, A-kinase anchor protein 4 (AKAP4) and centrin 1. Spermatozoa showed DFS defect associated with anomalies in head-tail attachment detected by SEM and TEM. Immunolocalisation of tubulin, AKAP4 and centrin 1 confirmed these alterations. Centrin 1 was visible in 67% of spermatozoa (in only 13% centrin localised in a normal position); in the majority of sperm centrin 1's location was altered, sometimes bent; often four spots, indicating the presence of two implantation fossae, were detected. At the centriolar level, immunoreactive fragments, frequently invading the entire short and thick tail, were observed. Centrin 1 is an essential component of the spermatozoa connecting piece and plays a role in centrosome dynamics during sperm morphogenesis and in zygotes and early embryos during spindle assembly. It is important to shed light on these rare conditions in order to better manage the patients during assisted reproductive technology.

NADPH oxidase activation and 4-hydroxy-2-nonenal/aquaporin-4 adducts as possible new players in oxidative neuronal damage presents in drug-resistant epilepsy.

A correlation between epilepsy and cellular redox imbalance has been suggested, although the mechanism by which oxidative stress (OS) can be implicated in this disorder is not clear. In the present study several oxidative stress markers and enzymes involved in OS have been determined. In particular, we examined the levels of 4-hydroxy-2-nonenal protein adducts (HNE-PA), a by-product of lipid peroxidation, and the activation of NADPH oxidase 2 (NOX2), as cellular source of superoxide (O(2)(-)), in surgically resected epileptic tissue from drug-resistant patients (N=50). In addition, we investigated whether oxidative-mediated protein damage can affect aquaporin-4 (AQP4), a water channel implicated in brain excitability and epilepsy. Results showed high levels of HNE-PA in epileptic hippocampus, in both neurons and glial cells and cytoplasmic positivity for p47(phox) and p67(phox) suggesting NOX2 activation. Interestingly, in epileptic tissue immunohistochemical localization of AQP4 was identified not only in perivascular astrocytic endfeet, but also in neurons. Nevertheless, negativity for AQP4 was observed in neurons in degeneration. Of note, HNE-mediated post-translational modifications of AQP4 were increased in epileptic tissues and double immunofluorescence clearly demonstrated co-localization of AQP4 and HNE-PA in epileptic hippocampal structures. The idea is that sudden, disorderly, and excessive neuronal discharges activates NOX2 with O(2)(-) production, leading to lipid peroxidation. The resulting generation of HNE targets AQP4, affecting water and ion balance. Therefore, we suggest that seizure induces oxidative damage as well as neuronal loss, thereby promoting neuronal hyperexcitability, also affecting water and ion balance by AQP4 modulation, and thus generating a vicious cycle.

SUMO1 in human sperm: new targets, role in motility and morphology and relationship with DNA damage.

In studies carried out previously, we demonstrated that small ubiquitin-like modifier 1 (SUMO1) is associated with poor sperm motility when evaluated with a protocol that reveals mostly SUMO1-ylated live sperm. Recently, with another protocol, it has been demonstrated that SUMO is expressed in most sperm and is related to poor morphology and motility, suggesting that sumoylation may have multiple roles depending on its localisation and targets. We show herein, by confocal microscopy and co-immunoprecipitation, that dynamin-related protein 1 (DRP1), Ran GTPase-activating protein 1 (RanGAP1) and Topoisomerase IIα, SUMO1 targets in somatic and/or germ cells, are SUMO1-ylated in mature human spermatozoa. DRP1 co-localises with SUMO1 in the mid-piece, whereas RanGAP1 and Topoisomerase IIα in the post-acrosomal region of the head. Both SUMO1 expression and co-localisation with the three proteins were significantly higher in morphologically abnormal sperm, suggesting that sumoylation represents a marker of defective sperm. DRP1 sumoylation at the mid-piece level was higher in the sperm of asthenospermic men. As in somatic cells, DRP1 sumoylation is associated with mitochondrial alterations, this protein may represent the link between SUMO and poor motility. As SUMO pathways are involved in responses to DNA damage, another aim of our study was to investigate the relationship between sumoylation and sperm DNA fragmentation (SDF). By flow cytometry, we demonstrated that SUMO1-ylation and SDF are correlated (r=0.4, P<0.02, n=37) and most sumoylated sperm shows DNA damage in co-localisation analysis. When SDF was induced by stressful conditions (freezing and thawing and oxidative stress), SUMO1-ylation increased. Following freezing and thawing, SUMO1-Topoisomerase IIα co-localisation and co-immunoprecipitation increased, suggesting an involvement in the formation/repair of DNA breakage.

Sumo1-ylation of human spermatozoa and its relationship with semen quality.

Sumoylation is a post-translational modification involved in the regulation of several cell functions. Recent studies suggest its involvement in spermatogenesis, but occurrence and function of SUMO (small ubiquitin-like modifier) in mature spermatozoa remain unknown. We report the occurrence of several SUMO1-conjugated proteins, in a range of 20-85 kDa, in ejaculated spermatozoa. By cytofluorimetric analysis, we evaluated the percentage of SUMO1-positive spermatozoa in 58 subjects undergoing semen analysis in our laboratory and correlated the obtained values with semen parameters. We found that the percentage of SUMO1-positive spermatozoa was inversely correlated with total (r = -0.35, p < 0.01) and progressive motility (r = -0.29, p < 0.05). Such correlations become stricter when only asthenospermic subjects were included in the analysis (r = -0.58, p = 0.01 for progressive motility, n = 17) and were lost in non-asthenospermic subjects. By immunofluorescence and immunoconfocal fluorescence, we demonstrated that SUMO1 is mainly located in the nucleus and, occasionally, in the midpiece of spermatozoa. Immunoelectron microscopy as well as a long permeabilization protocol demonstrated a massive localization of SUMO-1 in the nucleus. By using a fluorescent probe to distinguish dead/live cells, we show that SUMO1 is mainly present in live spermatozoa. In conclusion, sumoylation of human spermatozoa may be involved in the regulation of motility.

Primary neoplasms of the small bowel at CT: a pictorial essay for the clinician.

OBJECTIVE: Primary small intestinal neoplasms are uncommon tumors that are often small and difficult to identify. The aim of this paper is to describe CT technique and features in detecting and characterizing the tumors of the small bowel. MATERIALS AND METHODS: This paper focuses on radiological characteristics of benign and malignant primary neoplasms of the small bowel at CT, with special reference to multidetector-CT techniques, type and modality of administration of contrast agents (by oral route or CT-enterography and by nasojejunal tube or CT-enteroclysis). This paper will also provide pictures and description of CT findings of benign and malignant primary neoplasms using examples of CT-enterography and CT-enteroclysis. RESULTS: Among CT modalities, CT-enterography has the advantage of defining the real extension of wall lesions, possible transmural extension, the degree of mesenteric involvement and remote metastasis. Other useful modalities for the diagnosis of such lesions like capsule endoscopy and enteroscopy, provide important information but limited to mucosal changes with lower accuracy on extension and bowel wall involvement or submucosal lesions. CONCLUSIONS: Multidetector-CT, performed after distension of the small bowel with oral contrast material and intravenous injection of iodinated contrast material, is a useful method for the diagnosis and staging of small bowel neoplasms.

Gastro-oesophageal reflux and interstitial lung disease.

BACKGROUND: Interstitial lung disease is a heterogeneous entity, which encompasses a large number of pulmonary disorders, including idiopathic pulmonary fibrosis. Gastro-oesophageal reflux appears to be more prevalent in idiopathic pulmonary fibrosis than in controls and in patients with secondary pulmonary fibrosis, but its contribution to interstitial lung disease remains unsettled. AIMS: To prospectively evaluate gastro-oesophageal reflux in patients with interstitial lung disease and to define acid reflux patterns in patients with idiopathic and secondary forms of pulmonary fibrosis. MATERIALS AND METHODS: Twenty-eight patients (15M, median age 66 years, interquartile range 60-71) were studied by history taking, pulmonary function tests, high resolution computed tomography, oesophageal manometry and 24h oesophago-gastric pH monitoring. RESULTS: Sixteen patients (57%) had typical reflux symptoms. All patients completed 24h pH metry and 14 underwent oesophageal manometry. An abnormal oesophageal acid exposure was observed in 19 patients (68%), 13 of which complained of predominant typical reflux symptoms. A diagnosis of idiopathic pulmonary fibrosis was made in 18 patients, while the remaining 10 patients were classified as secondary pulmonary fibrosis. Secondary pulmonary fibrosis patients had more restrictive lung defect, as expressed as Tiffeneau index (p<0.05) and greater acid reflux at nighttime (p<0.05) than idiopathic pulmonary fibrosis patients. CONCLUSIONS: The prevalence of abnormal acid reflux in interstitial lung disease patients is high and, in particular, patients with secondary pulmonary fibrosis show higher oesophageal acid exposure than those with idiopathic form.

Water/cortical bone decomposition: A new approach in dual energy CT imaging for bone marrow oedema detection. A feasibility study.

INTRODUCTION: Many studies aimed at validating the application of Dual Energy Computed Tomography (DECT) in clinical practice where conventional CT is not exhaustive. An example is given by bone marrow oedema detection, in which DECT based on water/calcium (W/Ca) decomposition was applied. In this paper a new DECT approach, based on water/cortical bone (W/CB) decomposition, was investigated. MATERIALS AND METHODS: Eight patients suffering from marrow oedema were scanned with MRI and DECT. Two-materials density decomposition was performed in ROIs corresponding to normal bone marrow and oedema. These regions were drawn on DECT images using MRI informations. Both W/Ca and W/CB were considered as material basis. Scatter plots of W/Ca and W/CB concentrations were made for each ROI in order to evaluate if oedema could be distinguished from normal bone marrow. Thresholds were defined on the scatter plots in order to produce DECT images where oedema regions were highlighted through color maps. The agreement between these images and MR was scored by two expert radiologists. RESULTS: For all the patients, the best scores were obtained using W/CB density decomposition. CONCLUSIONS: In all cases, DECT color map images based on W/CB decomposition showed better agreement with MR in bone marrow oedema identification with respect to W/Ca decomposition. This result encourages further studies in order to evaluate if DECT based on W/CB decomposition could be an alternative technique to MR, which would be important when short scanning duration is relevant, as in the case of aged or traumatic patients.

Primary and secondary structure of a pore-forming toxin from the sea anemone, Actinia equina L., and its association with lipid vesicles.

The complete amino acid sequence of equinatoxin II, a potent pore-forming toxin with hemolytic, cytotoxic and cardiotoxic activity from the venom of the sea anemone, Actinia equina L., is reported. In addition, circular dicroism was used to estimate the secondary structure of this toxin either in the water-soluble or in the membrane-anchored form. Equinatoxin II when in water was found to contain about 29-33% of alpha-helical structure, 53-58% of beta-strand+beta-turn and 10-16% of random structure. Upon association with phospholipids, in particular with sphingomyelin, a rearrangement of the secondary structure occurs resulting in an increase of the alpha-helix content. An amphiphilic alpha-helical segment is predicted at the N-terminus, which shares structural homology with membrane active peptides like melittin and viral fusion peptides. In analogy to the behaviour of these peptides we propose that at least part of the alpha-helix content increase of equinatoxin II is due to the insertion of its N-terminus into the lipid bilayer. As in the case of melittin, association of 3-4 equinatoxin molecules is necessary to induce membrane permeabilisation.

Placenta expresses anti-Müllerian hormone and its receptor: Sex-related difference in fetal membranes.

INTRODUCTION: Anti-Müllerian hormone (AMH) is a member of the transforming growth factor-ß superfamily, playing a role in sexual differentiation and recruitment. Since a correlation exists between AMH serum levels in cord blood and fetal sex, the present study aimed to identify mRNA and protein expression of AMH and AMHRII in placenta and fetal membranes according to fetal sex. METHODS: Placenta and fetal membranes samples (n = 40) were collected from women with singleton uncomplicated pregnancies at term. Identification of AMH protein in placenta and fetal membranes was carried out by immunohistochemistry and AMH and AMHRII protein localization by immunofluorescence, while mRNA expression was assessed by quantitative real-time PCR. RESULT: AMH and AMHRII mRNAs were expressed by placenta and fetal membranes at term, without any significant difference between males and females. Placental immunostaining showed a syncytial localization of AMH without sex-related differences; while fetal membranes immunostaining was significantly more intense in male than in female fetuses (p < 0,01). Immunofluorescence showed an intense co-localization of AMH and AMHRII in placenta and fetal membranes. DISCUSSION: The present study for the first time demonstrated that human placenta and fetal membranes expresses and co-localizes AMH and AMHRII. Although no sex-related difference was found for the mRNA expression both in placenta and fetal membranes, a most intense staining for AMH in male fetal membranes supports AMH as a gender specific hormone.

Properties of Pseudomonas aeruginosa exotoxin A ionic channel incorporated in planar lipid bilayers.

Acidic conditions induce the incorporation of Pseudomonas aeruginosa exotoxin A into phospholipid planar bilayers and the formation of pores permeable to electrolytes. Channel openings occur as single events, although they may occasionally cluster in bursts. In 100 mM KCl, the elementary single channel current amplitude is 3.1 pA (at a transmembrane voltage of 100 mV), the mean open time is 1.3 ms, while bursts may last for several seconds. Noise analysis gave results identical to single channel analysis. Voltage pulse protocols and continuous cycling voltage ramps showed that the toxin channel is voltage dependent, having a higher probability of being open at positive voltages.

Mechanism of action of equinatoxin II, a cytolysin from the sea anemone Actinia equina L. belonging to the family of actinoporins.

Actinia equina equinatoxin II (EqT-II) is a representative of a family of pore-forming, basic, polypeptide toxins from sea anemones, now called actinoporins. This family comprises at least 27 members, which are all hemolytic at rather low concentrations. Red blood cell (RBC) hemolysis by EqT-II is the result of a colloid-osmotic shock caused by the opening of toxin-induced pores. Using osmotic protectants of different size the functional radius of the lesion was estimated to be approximately 1.1 nm. These pores are most probably constituted by oligomeric aggregates of cytolysin molecules, whose presence on the membrane of lysed RBC was directly demonstrated by polyacrylamide gel electrophoresis (PAGE) after covalent cross-linking. EqT-II is active also against a variety of mammalian cells including leukocytes, platelets and cardiomiocytes. An increased permeability of the plasma membrane after Eq-II attack is compatible with the notion that the toxin forms pores also on these cells. Eq-II permeabilises even purely lipidic model membranes, suggesting a protein receptor is not necessary. Using calcein-loaded unilamellar vesicles (UVs) comprised of phosphatydylcholine (PC) mixed with other lipids we observed that the rate and extent of permeabilization greatly increases when sphingomyelin (SM) or the ganglioside GM1 were introduced, particularly in the case of large UVs (which are more sensitive to the toxin than small UVs). PAGE indicated that the increased effect of Eq-II on SM containing vesicles is due to an increased level of toxin binding to such vesicles. The formation of cation-selective channels by EqT-II was directly demonstrated using planar lipid membranes where the toxin induced discrete increases of the film conductivity. The conductance of the channel was consistent with the estimated size of the lesion formed in RBC. Several factors can affect toxin activity: serum, low pH, low ionic strength and multivalent cations are potent inhibitors. pH Dependence is bell shaped, optimum activity being between pH 8 and 9. Similarly the action of Ca2+ is also bivalent: up to a concentration of approximately 2 mM it stimulates hemolysis, but above this concentration it inhibits (with 50% inhibition occurring at approximately 10 mM). When the known amino acid sequences of actinoporins are examined a common trait emerges; the presence of a well conserved, amphiphilic, putative alpha-helix at the N-terminus, which might be involved in the insertion of EqT-II in lipid membranes.

["CLAPSEN", a global approach to the rehabilitation of severe childhood malnutrition in Bolivia]. / Le <>, une démarche globale pour la réhabilitation nutritionnelle de l'enfant gravement mal nourri en Bolivie.

The "CLAPSEN" approach was developed at the Hospital Materno Infantil German Urquidi in Cochabamba, to provide a global response for the study and treatment of childhood malnutrition. "CLAPSEN" is short for Clinical, Laboratory, Anthropometry, Psychology, Sociology, Nursing (Enfermera in Spanish) and Nutritional care. Most of the malnourished children admitted to Cochabamba Hospital are from poor families, more than three quarters of whom have only recently arrived in the city. Acute malnutrition is just one of the manifestations of a generally unfavorable environment. Malnutrition should not be considered as a simple deficiency in energy, protein or micronutrients, but rather as a multi-deficiency syndrome, also involving a lack of basic health and social care. This study demonstrates that malnourished children display a considerable degree of psychological retardation and of immune system depression. After five weeks of rehabilitation, the children were considered to have recuperated physically, as assessed by anthropometry, but not psychologically, as assessed by the adapted Dewer Score, or immunologically, as shown by the size of the thymus or the extent of maturation of lymphocytes. This strategy was not designed as a long-term approach for treating malnutrition, but rather as a research project to characterize the children arriving at the hospital, to determine the reasons for their malnutrition and to identify strategies that could be implemented earlier by health centers of social services, to prevent deterioration in the condition of these children to severe malnutrition requiring hospital admission. We believe that, in this Latin American context, in which the rate of acute malnutrition is low, the hospital should continue to be involved in the treatment of severely malnourished children with associated diseases. The child's stay in hospital should be short and once the child has recovered clinically, he should be sent home. In light of the observed levels of social deprivation, psychosocial and immune deficits, there appears to be a need for continued support for the family, to ensure the full recovery of the child and to prevent relapses.

[Immuno-nutritional recovery of children with severe malnutrition]. / Réhabilitation immunonutritionnelle d'enfants atteints de malnutrition sévère.

In developing countries, more than 12 million children die each year from the combined effects of malnutrition and infection. Malnourished children have impaired cellular immunity and are particularly sensitive to opportunistic infections. However, immune recovery has rarely been investigated during nutritional rehabilitation. Indeed, mortality remains high during renutrition, and relapses are frequent. We established a center in Cochabamba, Bolivia, specifically to save these children by treating both clinical and nutritional problems and restoring immune function. The CRIN (center for immuno-nutritional recovery) admits children with severe malnutrition from the Cochabamba suburban area. They are from low income families, in crowded living conditions with poor sanitation and are weaned early. Nutritional diagnosis was based on weight-for-height, arm to head circumference ratio and clinical examination for edema, loss of subcutaneous tissue and diminished muscle mass. The children were examined daily, and first treated for respiratory and intestinal infections. Sociological and psychological aspects were also included in our holistic approach to treating severe malnutrition. Children received a four-stage diet lasting 2 months. During the initial phase (1 week) they were given an oil-sugar-milk based diet, with half lactose concentration, seven times a day. This supplied 1.5 to 2.5 g of protein and 120 to 150 kcal/kg of body weight, according to the PEM pattern. Protein and energy intake was then slowly increased during the transition phase (1 week). During the next, 'calorific-protein bombing' phase (6 weeks) 5 g of protein and 200 kcal/kg of body weight were given daily, such that there was sufficient energy for protein accumulation. During the last, discharge phase (1 week), the protein and energy contents were slowly decreased. Weight, height, arm and head circumferences, and triceps skin-fold thickness were measured weekly by standardized methods. Thymus size was assessed weekly by mediastinal ultrasound scanning with a portable scanner (ALOKA SSD-210 DXII, Tokyo) using a 5 MHz linear pediatric probe. Lymphocyte subpopulations in peripheral blood were investigated monthly using monoclonal antibodies. Compared to controls, the malnourished group had severe involution of the thymus, a significantly higher proportion of circulating immature T lymphocytes and a lower proportion of mature T lymphocytes. The two month longitudinal study showed that normal anthropometric values (90% NCHS weight for height) were recovered after one month of rehabilitation. However, immune recovery (thymic area of 350 nm2) required two months. This may explain the frequent relapses among malnourished children discharged after one month on the basis of 'apparent nutritional health'. Such children may remain immunodepressed, and should therefore be considered as high risk children. To test an immunostimulatory treatment, we designed a historical cohort study of malnourished children who received 2 mg of zinc per day. The children were matched for age, sex, anthropometric criteria and nutritional status with malnourished control children (treated previously with zinc). Anthropometric recovery was obtained in both groups in one month. Children receiving zinc attained immunological recovery within one month, whereas children not receiving zinc took two months. Thus zinc hastened immunological recovery concomitant with nutritional recovery such that the duration of hospitalization could be halved: after one month of this immuno-nutritional treatment, malnourished children appear to be sufficiently healthy to face their pathogenic home environment.

Hypoxia induces cell damage via oxidative stress in retinal epithelial cells.

Retinal diseases (RD), including diabetic retinopathy, are among the most important eye diseases in industrialized countries. RD is characterized by abnormal angiogenesis associated with an increase in cell proliferation and apoptosis. Hypoxia could be one of the triggers of the pathogenic mechanism of this disease. A key regulatory component of the cell's hypoxia response system is hypoxia-inducible factor 1 alpha (HIF-1α). It has been demonstrated that the induction of HIF-1α expression can be also achieved in vitro by exposure with cobalt chloride (CoCl2), leading to an intracellular hypoxia-like state. In this study we have investigated the effects of CoCl2 on human retinal epithelium cells (hRPE), which are an integral part of the blood-retinal barrier, with the aim to determine the possible role of oxidative stress in chemical hypoxia-induced damage in retinal epithelial cells. Our data showed that CoCl2 treatment is able to induce HIF-1α expression, that parallels with the formation of reactive oxygen species (ROS) and the increase of lipid 8-isoprostanes and 4-hydroxynonenal (4-HNE) protein adducts levels. In addition we observed the activation of the redox-sensitive transcription factor nuclear factor-kappaB (NFkB) by CoCl2 which can explain the increased levels of vascular endothelial growth factor (VEGF). The increased number of dead cells seems to be related to an apoptotic process. Taken together these evidences suggest that oxidative stress induced by hypoxia might be involved in RD development through the stimulation of two key-events of RD such as neo-angiogenesis and apoptosis.

Resveratrol protects SR-B1 levels in keratinocytes exposed to cigarette smoke.

Cigarette smoking (CS) has been strongly linked to several health conditions including heart disease, lung cancer, and other respiratory and circulatory ailments. Deleterious effects of cigarette smoking on skin have also been well documented, but unlike effects on other organs, damage does not depend upon inhalation. The upper layer of the skin, the stratum corneum (rich in cholesterol fatty acids and ceramide), is very susceptible to damage induced by exposure to environmental stressors that can modify its lipid composition and thereby affect its function of protecting skin from dehydration. Scavenger receptor B1 (SR-B1) is involved in the uptake of cholesterol in several tissues including skin. We previously demonstrated that CS exposure induces formation of aldehyde (HNE) adducts that decrease SR-B1 expression. As topical resveratrol, a well-known polyphenolic stilbene, has been demonstrated to show benefits against skin disorders, we investigated its possible role as a protective agent against CS-induced reduction of SR-B1 expression in cutaneous tissue. In this study, we demonstrate that resveratrol at doses ranging from 0.5 to 10 µM is not toxic and is able to increase SR-B1 protein levels in a dose-dependent manner in human keratinocytes. Moreover, when the cells that were pretreated with various doses of resveratrol were exposed to CS, the loss of SR-B1 was prevented in a dose-dependent manner. In addition, in keratinocytes, resveratrol was also able to prevent an increase in HNE-protein adducts induced by CS. In particular resveratrol was able to prevent HNE-SR-B1 adduct formation. Thus, resveratrol seems to be a natural compound that could provide skin with a defense against exogenous stressors by protecting the essential cholesterol receptor, SR-B1.

All solution processed low turn-on voltage near infrared LEDs based on core-shell PbS-CdS quantum dots with inverted device structure.

Colloidal semiconductor quantum dots (QDs) are extraordinarily appealing for the development of light emitting devices (LEDs) due to tunable and pure color emission, brightness and solution processability. This last advantage of the QD-LEDs is even more evident in the field of infrared emission where the devices currently used are prepared by high cost epitaxial techniques. Here we show the fabrication of low cost NIR QD-LEDs based on high quantum yield core-shell PbS-CdS QDs and a novel inverted device structure. Devices are produced using SnO2:F (FTO) as the conductive transparent contact, nanostructured TiO2 as the electron transport layer (ETL) and poly(3-hexylthiophene) P3HT as the hole transport layer (HTL). Despite the roughness of this ETL, the obtained external quantum efficiencies (EQEs) are similar to previously reported values, obtained with regular configuration and more expensive ITO substrates. A turn-on voltage as low as the QD band gap (1.47 eV) is achieved for a large area (1.54 cm(2)) and relatively stable QD-LEDs.

IL-1ß induces GFAP expression in vitro and in vivo and protects neurons from traumatic injury-associated apoptosis in rat brain striatum via NFκB/Ca²âº-calmodulin/ERK mitogen-activated protein kinase signaling pathway.

Reactive astrogliosis, a feature of neuro-inflammation is induced by a number of endogenous mediators including cytokines. Despite interleukin-1 beta (IL-1ß) stands out as the major inducer of this process, the underlying mechanism and its role on neuronal viability remain elusive. We investigated in human astrocytoma cells and the rat brain striatum, the role of the nuclear factor-kB (NF-kB) intracellular Ca(2+) concentration ([Ca(2+)]i) calmodulin (CaM) and extracellular regulated mitogen-activated protein kinases (ERK1/2) in IL-1ß-induced expression of glial fibrillary acidic protein (GFAP) and neuronal apoptosis associated to a brain trauma. Cell data showed that IL-1ß (1 ng/ml) increased NF-kB, pERK1/2 and GFAP expression. Nevertheless, further increase in IL-1ß levels reversed progressively these responses. Preventing ERK1/2 activation with 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthiol]-butadiene antagonized IL-1ß-induced GFAP expression while inhibiting selectively nuclear translocation of NF-kB with caffeic-acid phenethyl-ester down-regulated both ERK1/2 and GFAP expression induced by IL-1ß. The GFAP response was also prevented by antagonizing selectively increase in [Ca(2+)]i, CaM activity or inducible nitric oxide synthase expression with respectively ryanodine plus 2-aminoethoxydiphenyl-borate, N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide hydrochloride and N-[(3-(aminomethyl)-phenyl]methyl]-ethanimidamide dihydrochloride. Data in vivo supported these findings and showed that GFAP expression induced by IL-1ß (50 ng/ml) correlated with attenuated glial scar formation and reduced neuronal apoptosis. Our data identified the NF-kB/Ca(2+)-CaM/ERK signaling pathway as a novel in vivo key regulator of IL-1ß-induced astrogliosis which may represent a potential target in neurodegeneration.