The interplay between chemical speciation and physiology determines the bioaccumulation and toxicity of Cu(II) and Cd(II) to Caenorhabditis elegans

Using the well‐documented model organism Caenorhabditis elegans, a combined analysis of metal speciation in the exposure medium and body burdens of metals (Zn, Cu and Cd) was performed, and factors that are predictive of toxicological endpoints in single metal and mixed metal exposures were identified. Cu, and to a lesser extent Cd, is found to associate with Escherichia coli in the exposure medium (the food source for C. elegans) as evidenced by the observed decrease in both their dissolved and free metal ion concentrations. Together with a critical analysis of literature data, our results suggest that free metal ion concentrations and thus aqueous uptake routes are the best predictor of internal concentrations under all conditions considered, and of metal toxicity in single metal exposures. Additional factors are involved in determining the toxicity of metal mixtures. In general, the eventual adverse effects of metals on biota are expected to be a consequence of the interplay between chemical speciation in the exposure medium, timescale of exposure, exposure route as well as the nature and timescale of the biotic handling pathways.     

Transient discoloration of the coronal fragment in intra-alveolar root fractures

Abstract – Background: Root fractures are a relatively rare type of injury with frequencies of 0.5–7% of traumatized permanent teeth. It is well known that teeth with intra‐alveolar root fractures have a good prognosis. The pulp remains vital in about 80% of these teeth. If pulp necrosis develops, this normally only occurs in the coronal fragment. Although several studies on intra‐alveolar root fractures have been published during the last decades, none have mentioned that transient discoloration can occur. The aim of our study was to study the frequency and prognosis for intra‐alveolar root fractures with discoloration. Material and methods: The material consisted of 42 permanent incisors from 21 boys and 18 girls aged 7–19 years (mean = 12.7, median 12.0). In two girls and one boy, two incisors exhibited concurrent intra‐alveolar root fractured. The follow‐up period ranged from 1 to 9 years. The colour changes were determined at each control by transillumination of the clinical crown from the facial and palatal surfaces. Electrometric sensibility was evaluated and compared to the values of adjacent teeth using an electric pulp tester. At the final clinical and radiographic control, the type of healing was registered. Results: Discoloration was found in nine teeth. The root development was completed in all these teeth. The discoloration disappeared within 4 weeks to 6 months in eight teeth. The sensibility, which was lost at the injury, followed the changes in discoloration, and all teeth had regained normal sensibility when the discoloration had disappeared. Only one tooth, which showed a greyish hue, developed pulp necrosis. Conclusion: Transient discoloration in intra‐alveolar fractures is relatively common and is indicative of a good prognosis for healing.     

Identification of rare copy number variants in high burden schizophrenia families

Over the last years, genome‐wide studies consistently showed an increased burden of rare copy number variants (CNVs) in schizophrenia patients, supporting the “common disease, rare variant” hypothesis in at least a subset of patients. We hypothesize that in families with a high burden of disease, and thus probably a high genetic load influencing disease susceptibility, rare CNVs might be involved in the etiology of schizophrenia. We performed a genome‐wide CNV analysis in the index patients of eight families with multiple schizophrenia affected members, and consecutively performed a detailed family analysis for the most relevant CNVs. One index patient showed a DRD5 containing duplication. A second index patient presented with an NRXN1 containing deletion and two adjacent duplications containing MYT1L and SNTG2. Detailed analysis in the subsequent families showed segregation of the identified CNVs. With this study we show the importance of screening high burden families for rare CNVs, which will not only broaden our knowledge concerning the molecular genetic mechanisms involved in schizophrenia but also allow the use of the obtained genetic data to provide better clinical care to these families in general and to non‐symptomatic causal CNV carriers in particular. © 2013 Wiley Periodicals, Inc.     

Randomized Controlled Trial to Compare Two Bone Substitutes in the Treatment of Bony Dehiscences

Aim: This in vivo split‐mouth randomized controlled trial compared a synthetic bone substitute with a bovine bone mineral to cover bone dehiscences after implant insertion. Materials and Methods: Fourteen patients received four to six implants to support an overdenture. Two comparable dehiscences within the same patient were first covered with a layer of autogenous bone, followed by a layer of either Bio‐Oss® (group 1; Geistlich Pharma AG, Wolhusen, Switzerland) or Straumann BoneCeramic® (group 2; Institut Straumann AG, Basel, Switzerland) and sealed by a resorbable membrane. The change in vertical dimension of the defect was measured at implant placement and at abutment connection (6.5 months). Clinical and radiological parameters were evaluated up to 1 year of loading. Results: The vertical size of the defect at surgery was 6.4 ± 1.6 mm for group 1 and 6.4 ± 2.2 mm for group 2 sites, measured from the implant shoulder. After 6.5 months, the depth of the defect was reduced to 1.5 ± 1.2 mm and 1.9 ± 1.2 mm for group 1 and group 2 sites, respectively (p > 0.05). No implants failed during follow‐up. Mean marginal bone loss over the SLActive surface was 0.94 mm (group 1), 0.81 mm (group 2), and 0.93 mm (group 3, no dehiscence) after 1 year of loading. Conclusion: Both bone substitutes behaved equally effectively.     

Sarcopenia and its relationship with bone mineral density in middle-aged and elderly European men

Summary

The aim of this study was to determine the relationship between reduced muscle mass (sarcopenia) and areal bone mineral density (BMD_a) in middle-aged and elderly community-dwelling European men. Men with sarcopenia had significantly lower BMD_a and were more likely to have osteoporosis compared with men without sarcopenia.

Introduction

In men, the relationship between reduced muscle mass (sarcopenia) and BMD_a is unclear. This study aimed to determine this relationship in middle-aged and elderly community-dwelling men.

Methods

Men aged 40–79 years from the Manchester (UK) and Leuven (Belgium) cohorts of the European Male Ageing Study were invited to attend for assessment including dual-energy X-ray absorptiometry, from which appendicular lean mass (aLM), fat mass (FM) and whole-body, spine and hip BMD_a were determined. Relative appendicular skeletal muscle mass (RASM) was calculated as aLM/height². Muscle strength was assessed in subjects from Leuven. Sarcopenia was defined by RASM at <7.26 kg/m² and by the recent definition of the European Working Group on Sarcopenia in Older People (RASM at <7.26 kg/m² plus low muscle function). Linear regression was used to determine the associations between aLM, FM, muscle strength and BMD_a and logistic regression to determine the association between sarcopenia and osteoporosis.

Results

Six hundred seventy-nine men with a mean age of 59.6 (SD?=?10.7), contributed data to the analysis; 11.9 % were sarcopenic by the conventional definition. After adjustment for age and centre, aLM, RASM and FM were positively associated with BMD_a. Men with RASM at <7.26 kg/m² had significantly lower BMD_a compared with those with RASM at ≥7.26 kg/m². In a multivariable model, aLM was most consistently associated with BMD_a. Men with sarcopenia were more likely to have osteoporosis compared with those with normal RASM (odds ratio?=?3.0; 95 % CI?=?1.6–5.8).

Conclusions

Sarcopenia is associated with low BMD_a and osteoporosis in middle-aged and elderly men. Further studies are necessary to assess whether maintaining muscle mass contributes to prevent osteoporosis.     

The role of mast cells in neuroinflammation

Mast cells (MCs) are densely granulated perivascular resident cells of hematopoietic origin and well known for their pathogenetic role in allergic and anaphylactic reactions. In addition, they are also involved in processes of innate and adaptive immunity. MCs can be activated in response to a wide range of stimuli, resulting in the release of not only pro-inflammatory, but also anti-inflammatory mediators. The patterns of secreted mediators depend upon the given stimuli and microenvironmental conditions, accordingly MCs have the ability to promote or attenuate inflammatory processes. Their presence in the central nervous system (CNS) has been recognized for more than a century. Since then a participation of MCs in various pathological processes in the CNS has been well documented. They can aggravate CNS damage in models of brain ischemia and hemorrhage, namely through increased blood–brain barrier damage, brain edema and hemorrhage formation and promotion of inflammatory responses to such events. In contrast, recent evidence suggests that MCs may have a protective role following traumatic brain injury by degrading pro-inflammatory cytokines via specific proteases. In neuroinflammatory diseases such as multiple sclerosis, the role of MCs seems to be ambiguous. MCs have been shown to be damaging, neuroprotective, or even dispensable, depending on the experimental protocols used. The role of MCs in the formation and progression of CNS tumors such as gliomas is complex and both positive and negative relationships between MC activity and tumor progression have been reported. In summary, MCs and their secreted mediators modulate inflammatory processes in multiple CNS pathologies and can thereby either contribute to neurological damage or confer neuroprotection. This review intends to give a concise overview of the regulatory roles of MCs in brain disease.