EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists

The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007. The document contains chapters on definitions and classification, we now also propose definitions for 'difficult to treat' rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between the upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed. This executive summary for otorhinolaryngologists focuses on the most important changes and issues for otorhinolaryngologists.

Cyclosporin A causes impairment of the ventral prostate tissue structure of Wistar rats

Cyclosporin A (CsA) is an immunosuppressive drug widely used in medicine to reduce the immune system activity and, therefore, the risk of organ rejection after transplantation. However, many side effects can be related to its use, such as, reduction in serum testosterone levels due to damage of the testis structure and, consequently, male infertility. The present study aims to evaluate the effects of chronic CsA administration on the ventral prostate tissue ( 1 5 mg/kg per d, for 56 days). Stereological, morphometrical, morphological and ultrastructural observations were employed. The plasmatic testosterone and glucose levels were measured. An androgen receptor (AR) immunohistochemical method was applied on ventral prostate sections. Apoptosis was detected with the terminal deoxynucleotidyl transferase dUTP nick end labeling technique. CsA treatment caused reduction in plasmatic testosterone levels and an increase in glycemia. The volume of all ventral prostate tissue components (lumen, epithelium and muscular and nonmuscular stroma) and ventral prostate weight were reduced in the CsA-treated group. Light and transmission electron microscopy confirmed epithelium atrophy of treated animals. There was no alteration of AR expression or apoptotic index. CsA chronic treatment in the therapeutic doses caused damage to prostate tissue of adult Wistar rats, probably due to increase in the glucose levels and reduction in the plasmatic testosterone levels.

Trasduzione del segnale e poliamine nell'apoptosi di cellule cardiache

Introduction: Apoptotic cell death of cardiomyocytes is involved in several cardiovascular diseases including ischemia, hypertrophy and heart failure, thus representing a potential therapeutic target. Apoptosis of cardiac cells can be induced experimentally by several stimuli including hypoxia, serum withdrawal or combination of both. Several lines of research suggest that neurohormonal mechanisms play a central role in the progression of heart failure. In particular, excessive activation of the sympathetic nervous system or the renin-angiotensin-aldosterone system is known to have deleterious effects on the heart. Recent studies report that norepinephrine (NE), the primary transmitter of sympathetic nervous system, and aldosterone (ALD), which is actively produced in failing human heart, are able to induce apoptosis of rat cardiomyocytes. Polyamines are biogenic amines involved in many cellular processes, including apoptosis. Actually it appears that these molecules can act as promoting, modulating or protective agents in apoptosis depending on apoptotic stimulus and cellular model. We have studied the involvement of polyamines in the apoptosis of cardiac cells induced in a model of simulated ischemia and following treatment with NE or ALD. Methods: H9c2 cardiomyoblasts were exposed to a condition of simulated ischemia, consisting of hypoxia plus serum deprivation. Cardiomyocyte cultures were prepared from 1-3 day-old neonatal Wistar rat hearts. Polyamine depletion was obtained by culturing the cells in the presence of α-difluoromethylornithine (DFMO). Polyamines were separated and quantified in acidic cellular extracts by HPLC after derivatization with dansyl chloride. Caspase activity was measured by the cleavage of the fluorogenic peptide substrate. Ornithine decarboxylase (ODC) activity was measured by estimation of the release of 14C-CO2 from 14C-ornithine. DNA fragmentation was visualized by the method of terminal transferase-mediated dUTP nick end-labeling (TUNEL), and DNA laddering on agarose gel electophoresis. Cytochrome c was detected by immunoflorescent staining. Activation of signal transduction pathways was investigated by western blotting. Results: The results indicate that simulated ischemia, NE and ALD cause an early induction of the activity of ornithine decarboxylase (ODC), the first enzyme in polyamine biosynthesis, followed by a later increase of caspase activity, a family of proteases that execute the death program and induce cell death. This effect was prevented in the presence of DFMO, an irreversible inhibitor of ODC, thus suggesting that polyamines are involved in the execution of the death program activated by these stimuli. In H9c2 cells DFMO inhibits several molecular events related to apoptosis that follow simulated ischemia, such as the release of cytochrome c from mitochondria, down-regulation of Bcl-xL, and DNA fragmentation. The anti-apoptotic protein survivin is down-regulated after ALD or NE treatement and polyamine depletion obtained by DFMO partially opposes survivin decrease. Moreover, a study of key signal transduction pathways governing cell death and survival, revealed an involvement of AMP activated protein kinase (AMPK) and AKT kinase, in the modulation by polyamines of the response of cardiomyocytes to NE. In fact polyamine depleted cells show an altered pattern of AMPK and AKT activation that may contrast apoptosis and appears to result from a differential effect on the specific phosphatases that dephosphorylate and switch off these signaling proteins. Conclusions: These results indicate that polyamines are involved in the execution of the death program activated in cardiac cells by heart failure-related stimuli, like ischemia, ALD and NE, and suggest that their apoptosis facilitating action is mediated by a network of specific phosphatases and kinases.

PPAR-gamma expression in peritoneal endometriotic lesions correlates with pain experienced by patients

Endometriosis is a significant gynecologic condition that can cause both pain and infertility and affects up to 15% of women during their reproductive years. In peritoneal endometriotic lesions, the expression of peroxisome proliferation-activated receptor gamma, a nuclear receptor with antiinflammatory and neuroprotective roles, is positively correlated with the pain reported by patients.

Dose-response effect of interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, and interferon-y on the in vitro production of epithelial neutrophil activating peptide-78 (ENA-78), IL-8, and IL-6 by human endometrial stromal cells

The production of epithelial neutrophil activating peptide-78 (NA-78) and the interleukins IL-8 and IL-6 by endometrial stromal cells is stimulated by pro-inflammatory interleukin-1 (IL-1) and tumour necrosis factor-α (TNF-α). IL-8 is suggested to play a role in the pathogenesis of endometriosis, and in these women the peritoneal fluid concentrations of ENA-78 and IL-8 are increased. TNF-α has been tested together with interferon-γ because of their cooperative stimulation of IL-6. The release of IL-8, however, is inhibited with increasing interferon levels. The aim of the study was the analysis of the production of ENA-78, IL-6 and IL-8 by cultured human endometrial stromal cells in the presence of varying concentrations of IL-1β, TNF-α, and interferon-γ.

Adiponectin isoform distribution in serum and in follicular fluid of women undergoing treatment by ICSI

Adiponectin is an adipokine, present in the circulation in comparatively high concentrations and different molecular weight isoforms. For the first time, the distribution of these isoforms in serum and follicular fluid (FF) and their usefulness as biological markers for infertility investigations was studied.

Increased endometrial placenta growth factor (PLGF) gene expression in women with successful implantation

To analyze the vascularization of the endometrium via hysteroscopy and to assess its correlation with angiogenic factor gene expression and embryo implantation rate.

Peroxisome proliferating activating receptor gamma-independent attenuation of interleukin 6 and interleukin 8 secretion from primary endometrial stromal cells by thiazolidinediones

To assess the effect of thiazolidinediones on the regulation of inflammatory cytokines related to endometriosis in endometrial tissue and determine whether these effects occur via activation of the peroxisome proliferating activating receptor gamma (PPAR)-γ.

Endometriosis-associated nerve fibers, peritoneal fluid cytokine concentrations, and pain in endometriotic lesions from different locations

To assess the relationship between endometriotic lesions with associated nerve fibers with both pain and peritoneal fluid (PF) cytokine concentrations based on lesion location.

A VEGETATION RECONSTRUCTION OF UNION COUNTY, PENNSYLVANIA DURING THE EARLY HISTORICAL PERIOD (1755-1855)

This thesis assesses relationships between vegetation and topography and the impact of human tree-cutting on the vegetation of Union County during the early historical era (1755-1855). I use early warrant maps and forestry maps from the Pennsylvania historical archives and a warrantee map from the Union County courthouse depicting the distribution of witness trees and non-tree surveyed markers (posts and stones) in early European settlement land surveys to reconstruct the vegetation and compare vegetation by broad scale (mountains and valleys) and local scale (topographic classes with mountains and valleys) topography. I calculated marker density based on 2 km x 2 km grid cells to assess tree-cutting impacts. Valleys were mostly forests dominated by white oak (Quercus alba) with abundant hickory (Carya spp.), pine (Pinus spp.), and black oak (Quercus velutina), while pine dominated what were mostly pine-oak forests in the mountains. Within the valleys, pine was strongly associated with hilltops, eastern hemlock (Tsuga canadensis) was abundant on north slopes, hickory was associated with south slopes, and riparian zones had high frequencies of ash (Fraxinus spp.) and hickory. In the mountains, white oak was infrequent on south slopes, chestnut (Castanea dentata) was more abundant on south slopes and ridgetops than north slopes and mountain coves, and white oak and maple (Acer spp.) were common in riparian zones. Marker density analysis suggests that trees were still common over most of the landscape by 1855. The findings suggest there were large differences in vegetation between valleys and mountains due in part to differences in elevation, and vegetation differed more by topographic classes in the valleys than in the mountains. Possible areas of tree-cutting were evenly distributed by topographic classes, suggesting Europeans settlers were clearing land and harvesting timber in most areas of Union County.

European Stroke Science Workshop

The European Stroke Organisation held its first European Stroke Science Workshop in Garmisch-Partenkirchen, Germany (December 15-17, 2011). Stroke experts based in Europe were invited to present and discuss their current research. The scope of the workshop was to review the most recent findings of selected topics in stroke, to exchange ideas, to stimulate new research, and to enhance collaboration between European stroke research groups. Seven scientific sessions were held, each starting with a keynote lecture to review the state of the art of the given topic, followed by 4 or 5 short presentations by experts. They were asked to limit their presentations to 10 slides containing only recent information. The meeting was organized by the executive committee of the European Stroke Organisation (Heinrich Mattle, chairman, Michael Brainin, Angel Chamorro, Werner Hacke, Didier Leys) and supported by the European Stroke Conference (Michael Hennerici). The following sections summarize the content of the workshop.

European Stroke Science Workshop

The European Stroke Organisation held its first European Stroke Science Workshop in Garmisch-Partenkirchen, Germany (December 15-17, 2011). Stroke experts based in Europe were invited to present and discuss their current research. The scope of the workshop was to review the most recent findings of selected topics in stroke, to exchange ideas, to stimulate new research, and to enhance collaboration between European stroke research groups. Seven scientific sessions were held, each starting with a keynote lecture to review the state of the art of the given topic, followed by 4 or 5 short presentations by experts. They were asked to limit their presentations to 10 slides containing only recent information. The meeting was organized by the executive committee of the European Stroke Organisation (Heinrich Mattle, chairman, Michael Brainin, Angel Chamorro, Werner Hacke, Didier Leys) and supported by the European Stroke Conference (Michael Hennerici). The following sections summarize the content of the workshop.