Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base

Metabotropic glutamate receptor 5 as a potential target for smoking cessation

Rationale Most habitual smokers find it difficult to quit smoking because they are dependent upon the nicotine present in tobacco smoke. Tobacco dependence is commonly treated pharmacologically using nicotine replacement therapy or drugs, such as varenicline, that target the nicotinic receptor. Relapse rates, however, remain high and there remains a need to develop novel non-nicotinic pharmacotherapies for the dependence that are more effective than existing treatments. Objective The purpose of this paper is to review the evidence from preclinical and clinical studies that drugs that antagonise the metabotropic glutamate receptor 5 (mGluR5) in the brain are likely to be efficacious as treatments for tobacco dependence. Results Imaging studies reveal that chronic exposure to tobacco smoke reduces the density of mGluR5s in human brain. Preclinical results demonstrate that negative allosteric modulators (NAMs) at mGluR5 attenuate both nicotine self-administration and the reinstatement of responding evoked by exposure to conditioned cues paired with nicotine delivery. They also attenuate the effects of nicotine on brain dopamine pathways implicated in addiction. Conclusions Although mGluR5 NAMs attenuate most of the key facets of nicotine dependence they potentiate the symptoms of nicotine withdrawal. This may limit their value as smoking cessation aids. The NAMs that have been employed most widely in preclinical studies of nicotine dependence have too many \u201coff target\u201d effects to be used clinically. However newer mGluR5 NAMs have been developed for clinical use in other indications. Future studies will determine if these agents can also be used effectively and safely to treat tobacco dependence

Stability of upper incisor inclination changes in Class II division 2 patients.

Contains fulltext : 53304.pdf (publisher's version ) (Closed access)The aim of this study was to evaluate the changes in incisor inclination following orthodontic treatment in Class II division 2 patients, and to assess the long-term stability after retention. Dental casts and cephalograms of 61 Class II division 2 patients (31 males and 30 females, mean age 13.4 years) with a closed lip seal were available before (T1), at the end of treatment (T2), and 3.5 years (mean) post-treatment (T3). A method of measuring upper incisor inclination on dental casts was developed for the purpose of the investigation. This involved placing markers on the study casts and then taking radiographs which were measured to establish the upper incisor inclination. Statistical analysis of the data included the calculation of mean values, standard deviation, standard errors, and ranges for each variable. Spearman ranked correlation coefficients were computed for selected model variables and scattergrams plotted. To investigate the influence of the chosen retention therapy, a Mann-Whitney U-test was used. The mean change in incisor inclination during orthodontic treatment was 15.2 degrees. There was a mean relapse of 2.2 degrees between T2 and T3, but this was not considered clinically relevant. The amount of relapse was independent of the type of the retention appliance (Hawley type retainer or lingual retainer). The relationship between long-term stability of the incisor inclination and between the lip line relative to the upper incisors was also investigated, based on cephalometric data. A mean decrease in lip line height of 0.6 mm was seen at T2 and, although the observed change was statistically significant, it would not be clinically relevant