Use of equine pericardium sheet (lyomesh®) as dura mater substitute in endoscopic endonasal transsphenoidal surgery

Objective: The aim of this study was to describe the use of equine pericardium sheet (Lyomesh®) as dural substitute for sellar reconstruction after endoscopic endonasal transsphenoidal surgery for the removal of pituitary adenomas. Methods: We reviewed data of patients that underwent surgery by means of an endoscopic endonasal transsphenoidal approach for the removal of pituitary adenomas over a 12-months period, starting in May 2012, i.e. when we adopted Lyomesh® (Audio Technologies, Piacenza, Italy) an equine pericardium sheet, as dura mater substitute. Results: During the 12-months period evaluated, we performed an endoscopic endonasal transsphenoidal operation for a variety of pituitary lesions on 102 consecutive patients. Among these, in 12 patients (9.4%) harboring a pituitary adenoma, the implant of the pericardium sheet was used. Four patients (33.3%) presented a small intraoperative cerebrospinal fluid (CSF) leak; in these cases the Lyomesh® was placed intradurally with fibrin glue and, thereafter, several layers were positioned in extradural space. In 8 other subjects without any evidence of CSF leak, the dural substitute was placed intradurally and fibrin glue was injected intradurally to hold the material in place. Conclusions: Even if based on a relatively small patient series, our experience demonstrated that the use of equine pericardium sheet (Lyomesh®) as dura mater substitute in transsphenoidal surgery is safe and biocompatible, as compared with other dural substitutes

The IκB-protein BCL-3 controls toll-like receptor-induced MAPK activity by promoting TPL-2 degradation in the nucleus

Proinflammatory responses induced by Toll-like receptors (TLRs) are dependent on the activation of the NF-ĸB and mitogen-activated protein kinase (MAPK) pathways, which coordinate the transcription and synthesis of proinflammatory cytokines. We demonstrate that BCL-3, a nuclear IĸB protein that regulates NF-ĸB, also controls TLR-induced MAPK activity by regulating the stability of the TPL-2 kinase. TPL-2 is essential for MAPK activation by TLR ligands, and the rapid proteasomal degradation of active TPL-2 is a critical mechanism limiting TLR-induced MAPK activity. We reveal that TPL-2 is a nucleocytoplasmic shuttling protein and identify the nucleus as the primary site for TPL-2 degradation. BCL-3 interacts with TPL-2 and promotes its degradation by promoting its nuclear localization. As a consequence, Bcl3−/− macrophages have increased TPL-2 stability following TLR stimulation, leading to increased MAPK activity and MAPK-dependent responses. Moreover, BCL-3–mediated regulation of TPL-2 stability sets the MAPK activation threshold and determines the amount of TLR ligand required to initiate the production of inflammatory cytokines. Thus, the nucleus is a key site in the regulation of TLR-induced MAPK activity. BCL-3 links control of the MAPK and NF-ĸB pathways in the nucleus, and BCL-3–mediated TPL-2 regulation impacts on the cellular decision to initiate proinflammatory cytokine production in response to TLR activation

Primary spinal glioblastoma multiforme. Single center experience and literature review

Abstract Objectives Spinal glioblastomas represent a rare entity accounting for ca 1–3% of all intramedullary tumors; data about survival, prognostic factors and therapeutic protocols are quite poor. Even with an aggressive multimodal management the spinal glioblastoma patients' survival remains poor, with rapid progression of the disease. This study reports our experience with the management of the primary intramedullary glioblastomas, also in regard to the current literature data. Patients and Methods We retrospectively analyzed the medical records of 5 patients treated at the Department for Neuro-oncology and Spine Surgery of the Clinical Center of Belgrade, Serbia, between January 2007 and December 2016 for a primary intramedullary glioblastoma. Demographic characteristics, pre-operative data and post-operative results were then compared with previous literature regarding spinal GBMs and attempt to identify potential prognostic factors. Results Gross total resection was achieved in two patients, while a subtotal resection was performed in the latter 3 cases; as per protocol, all patients underwent to surgery, followed by radio and chemotherapy. There were no intraoperative complications and no patients developed a new postoperative neurological defect; the median overall survival was 6 months. Progression or recurrence of disease was noted in all patients at the 3-months follow-up, despite the adjuvant treatments. Conclusions To the date, there is a lack of consensus on specific management of spinal glioblastomas: the extent of resection can play an important role, but it appears to be not preeminent. A shorter interval between symptoms onset and treatment and a smaller extension of the tumor seem to be correlated with better outcomes and a longer overall survival. However, there is not an adjunctive viable standardized postoperative therapy yet, which results in concrete and persistent improvement of overall survival and progression free survival

The antimicrobial peptide Magainin-2 interacts with BamA impairing folding of E. coli membrane proteins

: Antimicrobial peptides (AMPs) are a unique and diverse group of molecules endowed with a broad spectrum of antibiotics properties that are being considered as new alternative therapeutic agents. Most of these peptides are membrane-active molecules, killing bacteria by membrane disruption. However, recently an increasing number of AMPs was shown to enter bacterial cells and target intracellular processes fundamental for bacterial life. In this paper we investigated the mechanism of action of Maganin-2 (Mag-2), a well-known antimicrobial peptide isolated from the African clawed frog Xenopus laevis, by functional proteomic approaches. Several proteins belonging to E. coli macromolecular membrane complexes were identified as Mag-2 putative interactors. Among these, we focused our attention on BamA a membrane protein belonging to the BAM complex responsible for the folding and insertion of nascent β-barrel Outer Membrane Proteins (OMPs) in the outer membrane. In silico predictions by molecular modelling, in vitro fluorescence binding and Light Scattering experiments carried out using a recombinant form of BamA confirmed the formation of a stable Mag-2/BamA complex and indicated a high affinity of the peptide for BamA. Functional implications of this interactions were investigated by two alternative and complementary approaches. The amount of outer membrane proteins OmpA and OmpF produced in E. coli following Mag-2 incubation were evaluated by both western blot analysis and quantitative tandem mass spectrometry in Multiple Reaction Monitoring scan mode. In both experiments a gradual decrease in outer membrane proteins production with time was observed as a consequence of Mag-2 treatment. These results suggested BamA as a possible good target for the rational design of new antibiotics since this protein is responsible for a crucial biological event of bacterial life and is absent in humans

Defining the role of nuclear factor NF-κB p105 subunit in human macrophage by transcriptomic analysis of NFKB1 knockout THP-1 cells

Since its discovery over 30 years ago the NF-ĸB family of transcription factors has gained the status of master regulator of the immune response. Much of what we understand of the role of NF-ĸB in immune development, homeostasis and inflammation comes from studies of mice null for specific NF-ĸB subunit encoding genes. The role of inflammation in diseases that affect a majority of individuals with health problems globally further establishes NF-ĸB as an important pathogenic factor. More recently, genomic sequencing has revealed loss of function mutations in the NFKB1 gene as the most common monogenic cause of common variable immunodeficiencies in Europeans. NFKB1 encodes the p105 subunit of NF-ĸB which is processed to generate the NF-ĸB p50 subunit. NFKB1 is the most highly expressed transcription factor in macrophages, key cellular drivers of inflammation and immunity. Although a key role for NFKB1 in the control of the immune system is apparent from Nfkb1-/- mouse studies, we know relatively little of the role of NFKB1 in regulating human macrophage responses. In this study we use the THP1 monocyte cell line and CRISPR/Cas9 gene editing to generate a model of NFKB1-/- human macrophages. Transcriptomic analysis reveals that activated NFKB1-/- macrophages are more pro-inflammatory than wild type controls and express elevated levels of TNF, IL6, and IL1B, but also have reduced expression of co-stimulatory factors important for the activation of T cells and adaptive immune responses such as CD70, CD83 and CD209. NFKB1-/- THP1 macrophages recapitulate key observations in individuals with NFKB1 haploinsufficiency including decreased IL10 expression. These data supporting their utility as an in vitro model for understanding the role of NFKB1 in human monocytes and macrophages and indicate that of loss of function NFKB1 mutations in these cells is an important component in the associated pathology

The feasibility of three port endonasal, transorbital, and sublabial approach to the petroclival region: neurosurgical audit and multiportal anatomic quantitative investigation

Purpose: The petroclival region represents the "Achille's heel" for the neurosurgeons. Many ventral endoscopic routes to this region, mainly performed as isolated, have been described. The aim of the present study is to verify the feasibility of a modular, combined, multiportal approach to the petroclival region to overcome the limits of a single approach, in terms of exposure and working areas, brain retraction and manipulation of neurovascular structures. Methods: Four cadaver heads (8 sides) underwent endoscopic endonasal transclival, transorbital superior eyelid and contralateral sublabial transmaxillary-Caldwell-Luc approaches, to the petroclival region. CT scans were obtained before and after each approach to rigorously separate the contribution of each osteotomy and subsequentially to build a comprehensive 3D model of the progressively enlarged working area after each step. Results: The addition of the contralateral transmaxillary and transorbital corridors to the extended endoscopic endonasal transclival in a combined multiportal approach provides complementary paramedian trajectories to overcome the natural barrier represented by the parasellar and paraclival segments of the internal carotid artery, resulting in significantly greater area of exposure than a pure endonasal midline route (8,77 cm2 and 11,14 cm2 vs 4,68 cm2 and 5,83cm2, extradural and intradural, respectively). Conclusion: The use of different endoscopic "head-on" trajectories can be combined in a wider multiportal extended approach to improve the ventral route to the most inaccessible petroclival regions. Finally, by combining these approaches and reiterating the importance of multiportal strategy, we quantitatively demonstrate the possibility to reach "far away" paramedian petroclival targets while preserving the neurovascular structures

Diabetes and Obesity as Independent Risk Factors for Osteoporosis: Updated Results from the ROIS/EMEROS Registry in a Population of Five Thousand Post-Menopausal Women Living in a Region Characterized by Heavy Environmental Pressure

EMEROS/ROIS Registry is a project funded by ISBEM and supported by Medicina Futura Research