Human Stiff-Person Syndrome IgG Induces Anxious Behavior in Rats

Background: Anxiety is a heterogeneous behavioral domain playing a role in a variety of neuropsychiatric diseases. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases. Stiff person syndrome (SPS) is a CNS disorder characterized by increased muscle tone and prominent agoraphobia and anxiety. Most patients have high-titer antibodies against glutamate decarboxylase (GAD) 65. The pathogenic role of these autoantibodies is unclear. Methodology/Principal Findings: We re-investigated a 53 year old woman with SPS and profound anxiety for GABA-A receptor binding in the amygdala with (11)C-flumazenil PET scan and studied the potential pathogenic role of purified IgG from her plasma filtrates containing high-titer antibodies against GAD 65. We passively transferred the IgG fraction intrathecally into rats and analyzed the effects using behavioral and in vivo electrophysiological methods. In cell culture, we measured the effect of patient IgG on GABA release from hippocampal neurons. Repetitive intrathecal application of purified patient IgG in rats resulted in an anxious phenotype resembling the core symptoms of the patient. Patient IgG selectively bound to rat amygdala, hippocampus, and frontal cortical areas. In cultured rat hippocampal neurons, patient IgG inhibited GABA release. In line with these experimental results, the GABA-A receptor binding potential was reduced in the patient’s amygdala/hippocampus complex. No motor abnormalities were found in recipient rats. Conclusion/Significance: The observations in rats after passive transfer lead us to propose that anxiety-like behavior can be induced in rats by passive transfer of IgG from a SPS patient positive for anti-GAD 65 antibodies. Anxiety, in this case, thus may be an antibody-mediated phenomenon with consecutive disturbance of GABAergic signaling in the amygdala region

Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer

The prognosis of colon cancer (CC) is dictated by tumor-infiltrating lymphocytes, including follicular helper T (TFH) cells and the efficacy of chemotherapy-induced immune responses. It remains unclear whether gut microbes contribute to the elicitation of TFH cell-driven responses. Here, we show that the ileal microbiota dictates tolerogenic versus immunogenic cell death of ileal intestinal epithelial cells (IECs) and the accumulation of TFH cells in patients with CC and mice. Suppression of IEC apoptosis led to compromised chemotherapy-induced immunosurveillance against CC in mice. Protective immune responses against CC were associated with residence of Bacteroides fragilis and Erysipelotrichaceae in the ileum. In the presence of these commensals, apoptotic ileal IECs elicited PD-1+ TFH cells in an interleukin-1R1- and interleukin-12-dependent manner. The ileal microbiome governed the efficacy of chemotherapy and PD-1 blockade in CC independently of microsatellite instability. These findings demonstrate that immunogenic ileal apoptosis contributes to the prognosis of chemotherapy-treated CC

Corrosion behavior of dental alloys used for retention elements in prosthodontics

The purpose of this study was to investigate the corrosion behavior of 10 different high noble gold-based dental alloys, used for prosthodontic retention elements, according to ISO 10271. Samples of 10 high-noble and noble gold-based dental alloys were subjected to: (i) static immersion tests with subsequent analysis of ion release for eight different elements using mass spectrometry; (ii) electrochemical tests, including open-circuit potential and potentiodynamic scans; and (iii) scanning electron microscopy, followed by energy-dispersive X-ray microscopy. The results were analyzed using one-way ANOVA and Sidak multiple-comparisons post-hoc test at a level of significance of α = 0.05. Significant differences were found among the 10 alloys studied for all ions (P < 0.001). The potentiodynamic analysis showed values from -82.5 to 102.8 mV for the open-circuit potential and from 566.7 to 1367.5 mV for the breakdown potential. Both the open-circuit and the breakdown potential varied considerably among these alloys. Scanning electron microscopy analysis confirmed the existence of typically small-diameter corrosion defects, whilst the energy-dispersive X-ray analysis found no significant alteration in the elemental composition of the alloys. The results of this study reveal the variability in the corrosive resistance among the materials used for retention elements in prosthodontics

Interleukin-17 and type 17 helper T cells in cancer management and research

Nicolas J Llosa,1 Abby L Geis,2 Erik Thiele Orberg,2 Franck Housseau2 1Department of Pediatric Oncology, 2Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA Abstract: Since their recent discovery, T helper 17 (Th17) cells have been frequently detected in the tumor microenvironment of many malignancies, but their clinical implications remain largely unknown. Interleukin-17 (IL-17) detection is commonly related with poor outcomes in colorectal cancers, yet its presence is associated with antitumor responses in ovarian carcinomas. Numerous experimental models illustrate the divergent roles of Th17 cells in tumor immunity, which appears to be mainly dependent on the tumor context (type, location, and stage of cancer). It is recognized that IL-17 is produced by a variety of cell types and that Th17 cells are endowed with a unique functional plasticity. Therefore, when trying to elucidate potential immune biomarkers and immunotargets, it is extremely important to make a clear dissociation between strategies targeting Th17 versus its hallmark cytokine, IL-17. In this review, we will summarize the data regarding the detection of IL-17 and Th17 in human cancers, consider the experimental evidence on their respective roles in antitumor activity, and discuss the potential of IL-17 as an immune target for therapeutic interventions. Keywords: biomarkers, inflammation, tumor microenvironmen

Influence of a bonding agent on the bond strength between a dental Co-Cr alloy and nine different veneering porcelains

AbstractAdequate bonding between dental veneering porcelains and non-precious metal alloys is a main factor for the long-term functionality of porcelain fused to metal restorations. Although a huge number of veneering porcelains are on the market, only few studies have reported about the role of bonding agents for the bond strength at their respective interface to cobalt-chromium (Co-Cr). The aim of this study was to compare the influence of a metal-ceramic bonding agent for Co-Cr alloys on the bond strength of metal-ceramic systems. The bond strength test was done according to ISO 9693 with additional detection of the first acoustic crack initiated signal while testing. The bonding agent had only minor effects on the bond strength of the different Co-Cr/ceramic systems. Only three of the nine studied systems showed statistically significant differences (p&lt;0.05) upon applying the bonding agent. Scanning electron microscopy (SEM) showed cracks predominantly caused by adhesive failure. Based on this study, Co-Cr alloys veneered with porcelains with and without a bonding agent exceeded the minimum bond strength of 25 MPa required according to ISO 9693. However, if bond strength values based on acoustic signals were calculated, values below the threshold of 25 MPa could be observed. Such findings are important for failures caused by the occurrence of early cracks.</jats:p

Electrochemical Behaviour and Galvanic Effects of Titanium Implants Coupled to Metallic Suprastructures in Artificial Saliva

The aim of the present study is to analyze the electrochemical behavior of five different dental alloys: two cobalt-chromium alloys (CoCr and CoCr-c), one nickel-chromium-titanium alloy (NiCrTi), one gold-palladium alloy (Au), and one titanium alloy (Ti6Al4V), and the galvanic effect when they are coupled to titanium implants (TiG2). It was carried out by electrochemical techniques (open circuit measurements, potentiodynamic curves and Zero-Resistance Ammetry) in artificial saliva (AS), with and without fluorides in different acidic conditions. The studied alloys are spontaneously passivated, but NiCrTi alloy has a very narrow passive domain and losses its passivity in presence of fluorides, so is not considered as a good option for implant superstructures. Variations of pH from 6.5 to 3 in artificial saliva do not change the electrochemical behavior of Ti, Ti6Al4V, and CoCr alloys, and couples, but when the pH of the artificial saliva is below 3.5 and the fluoride content is 1000 ppm Ti and Ti6Al4V starts actively dissolving, and CoCr-c superstructures coupled to Ti show acceleration of corrosion due to galvanic effects. Thus, NiCrTi is not recommended for implant superstructures because of risk of Ni ion release to the body, and fluorides should be avoided in acidic media because Ti, Ti6Al4V, and CoCr-c superstructures show galvanic corrosion. The best combinations are Ti/Ti6Al4V and Ti/CoCr as alternative of noble gold alloys