Periodontal surgery in furcation-involved maxillary molars revisited—an introduction of guidelines for comprehensive treatment

Maxillary molars with interradicular loss of periodontal tissue have an increased risk of additional attachment loss with an impaired long-term prognosis. Since accurate clinical analysis of furcation involvement is not feasible due to limited access, morphological variations and measurement errors, additional diagnostics, e.g., with cone-beam computed tomography, may be required. Surgical treatment options have graduated from a less invasive approach, i.e., keeping as much periodontal attachment as possible, to a more invasive approach: (1) open flap debridement with/without gingivectomy or apically repositioned flap and/or tunnelling; (2) root separation; (3) amputation/trisection of a root (with/without root separation or tunnel preparation); (4) amputation/trisection of two roots; and (5) extraction of the entire tooth. Tunnelling is indicated when the degree of root separation allows for opening of the interradicular region. Alternatively, root separation is performed particularly in root-canal treated teeth with reduced coronal tooth substance requiring crown restorations. As soon as the attachment of one or two roots in maxillary molars is severely reduced, root removal is indicated and performed either as amputation or trisection including the corresponding part of the clinical crown. While the indication for regenerative measures in maxillary molars with furcation involvement is very limited, extraction and replacement with implants is restricted, particularly in sites requiring complex alveolar ridge augmentation and sinus elevation. A systematic approach for decision making in furcation-involved maxillary molars is described in this overview, including what constitutes accurate diagnosis and what indications there are for the different surgical periodontal treatment option

The role of the novel Th17 cytokine IL-26 in intestinal inflammation

Background and aims: Interleukin 26 (IL-26), a novel IL-10-like cytokine without a murine homologue, is expressed in T helper 1 (Th1) and Th17 cells. Currently, its function in human disease is completely unknown. The aim of this study was to analyse its role in intestinal inflammation.Methods: Expression studies were performed by reverse transcription-PCR (RT-PCR), quantitative PCR, western blot and immunohistochemistry. Signal transduction was analysed by western blot experiments and ELISA. Cell proliferation was measured by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. IL-26 serum levels were determined by an immunoluminometric assay (ILMA).Results: All examined intestinal epithelial cell (IEC) lines express both IL-26 receptor subunits IL-20R1 and IL-10R2. IL-26 activates extracellular signal-related kinase (ERK)-1/2 and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) mitogen-activated protein (MAP) kinases, Akt and signal transducers and activators of transcription (STAT) 1/3. IL-26 stimulation increases the mRNA expression of proinflammatory cytokines but decreases cell proliferation. In inflamed colonic lesions of patients with Crohn's disease, an elevated IL-26 mRNA expression was found that correlated highly with the IL-8 and IL-22 expression. Immunohistochemical analysis demonstrated IL-26 protein expression in colonic T cells including Th17 cells expressing the orphan nuclear receptor ROR\textgreekgt, with an increased number of colonic IL-26-expressing cells in active Crohn's disease.Conclusion: Intestinal cells express the functional IL-26 receptor complex. IL-26 modulates IEC proliferation and proinflammatory gene expression and its expression is upregulated in active Crohn's disease, indicating a role for this cytokine system in the innate host cell response during intestinal inflammation. For the first time, IL-26 expression is demonstrated in colonic ROR\textgreekgt-expressing Th17 cells in situ, supporting a role for this cell type in the pathogenesis of Crohn's disease

Head Coverings in the Courtroom: A Question of Respect for the Judge or of Judicial Tolerance?

The Human Rights Centre at Ghent University (the HRC) first initiated the present research while preparing an amicus curiae brief in the Lachiri v. Belgium case before the European Court of Human Rights (ECtHR). The applicant in Lachiri, who was a civil party in legal proceedings concerning the murder of her brother, was denied access to a Brussels courtroom after refusing to remove her Islamic headscarf . Ms. Lachiri’s admission was refused in reliance on Article 759 of the Belgian Judicial Code (Gerechtelijk Wetboek/ Code Judiciaire), which provides that “[t]he audience will attend the sessions with their heads uncovered, respectfully and silently; whatever the judge commands for the maintenance of order will be punctually and immediately executed.” In its third-party intervention, the HRC sought to supply the ECtHR with additional information concerning three points: the debate on the wearing of Islamic headscarves in Belgium, the history, object and purpose of Article 759 of the Belgian Judicial Code, and the scope of the State margin of appreciation in prohibiting religious items of clothing

Use of Modified Clostridium perfringens Enterotoxin Fragments for Claudin Targeting in Liver and Skin Cells

Claudins regulate paracellular permeability in different tissues. The claudin-binding domain of Clostridium perfringens enterotoxin (cCPE) is a known modulator of a claudin subset. However, it does not efficiently bind to claudin-1 (Cldn1). Cldn1 is a pharmacological target since it is (i) an essential co-receptor for hepatitis C virus (HCV) infections and (ii) a key element of the epidermal barrier limiting drug delivery. In this study, we investigated the potential of a Cldn1-binding cCPE mutant (i) to inhibit HCV entry into hepatocytes and (ii) to open the epidermal barrier. Inhibition of HCV infection by blocking of Cldn1 with cCPE variants was analyzed in the Huh7.5 hepatoma cell line. A model of reconstructed human epidermis was used to investigate modulation of the epidermal barrier by cCPE variants. In contrast to cCPEwt, the Cldn1-binding cCPE-S305P/S307R/S313H inhibited infection of Huh7.5 cells with HCV in a dose-dependent manner. In addition, TJ modulation by cCPE variant-mediated targeting of Cldn1 and Cldn4 opened the epidermal barrier in reconstructed human epidermis. cCPE variants are potent claudin modulators. They can be applied for mechanistic in vitro studies and might also be used as biologics for therapeutic claudin targeting including HCV treatment (host-targeting antivirals) and improvement of drug delivery

Effect of Membrane Exposure on Guided Bone Regeneration: A Systematic Review and Meta‐Analysis

Aims: This review aimed at investigating the effect of membrane exposure on guided bone regeneration (GBR) outcomes at peri-implant sites and edentulous ridges. Material and Methods: Electronic and manual literature searches were conducted by two independent reviewers using four databases, including MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials, for articles up to February 2017. Articles were included if they were human clinical trials or case series reporting outcomes of GBR procedures with and without membrane exposure. A random-effects meta-analysis was conducted, and the weighted mean difference (WMD) between the two groups and 95% confidence interval (CI) were reported. Results: Overall, eight articles were included in the quantitative analysis. The WMD of the horizontal bone gain at edentulous ridges was −76.24% (95% CI = −137.52% to −14.97%, p = .01) between sites with membrane exposure and without exposure. In addition, the WMD of the dehiscence reduction at peri- implant sites was −27.27% (95% CI of −45.87% to −8.68%, p = .004). Both analyses showed significantly favorable outcomes at the sites without membrane exposure. Conclusion: Based on the findings of this study, membrane exposure after GBR procedures has a significant detrimental influence on the outcome of bone augmentation. For the edentulous ridges, the sites without membrane exposure achieved 74% more horizontal bone gain than the sites with exposure. For peri-implant dehiscence defects, the sites without membrane exposure had 27% more defect reduction than the sites with exposure

The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel

Deletion of the Androgen Receptor in Adipose Tissue in Male Mice Elevates Retinol Binding Protein 4 and Reveals Independent Effects on Visceral Fat Mass and on Glucose Homeostasis

Testosterone deficiency is epidemic in obese ageing males with type 2 diabetes, but the direction of causality remains unclear. Testosterone-deficient males and global androgen receptor (AR) knockout mice are insulin resistant with increased fat, but it is unclear whether AR signaling in adipose tissue mediates body fat redistribution and alters glucose homoeostasis. To investigate this, mice with selective knockdown of AR in adipocytes (fARKO) were generated. Male fARKO mice on normal diet had reduced perigonadal fat but were hyperinsulinemic and by age 12 months, were insulin deficient in the absence of obesity. On high-fat diet, fARKO mice had impaired compensatory insulin secretion and hyperglycemia, with increased susceptibility to visceral obesity. Adipokine screening in fARKO mice revealed a selective increase in plasma and intra-adipose retinol binding protein 4 (RBP4) that preceded obesity. AR activation in murine 3T3 adipocytes downregulated RBP4 mRNA. We conclude that AR signaling in adipocytes not only protects against high-fat diet–induced visceral obesity but also regulates insulin action and glucose homeostasis, independently of adiposity. Androgen deficiency in adipocytes in mice resembles human type 2 diabetes, with early insulin resistance and evolving insulin deficiency

Peri-implant diseases: Consensus Report of the Sixth European Workshop on Periodontology

Issues related to peri-implant disease were discussed. It was observed that the most common lesions that occur, i.e. peri-implant mucositis and peri-implantitis are caused by bacteria. While the lesion of peri-implant mucositis resides in the soft tissues, peri-implantitis also affects the supporting bone. Peri-implant mucositis occurs in about 80% of subjects (50% of sites) restored with implants, and peri-implantitis in between 28% and 56% of subjects (12-40% of sites). A number of risk indicators were identified including (i) poor oral hygiene, (ii) a history of periodontitis, (iii) diabetes and (iv) smoking. It was concluded that the treatment of peri-implant disease must include anti-infective measures. With respect to peri-implant mucositis, it appeared that non-surgical mechanical therapy caused the reduction in inflammation (bleeding on probing) but also that the adjunctive use of antimicrobial mouthrinses had a positive effect. It was agreed that the outcome of non-surgical treatment of peri-implantitis was unpredictable. The primary objective of surgical treatment in peri-implantitis is to get access to the implant surface for debridement and decontamination in order to achieve resolution of the inflammatory lesion. There was limited evidence that such treatment with the adjunctive use of systemic antibiotics could resolve a number of peri-implantitis lesions. There was no evidence that so-called regenerative procedures had additional beneficial effects on treatment outcome