Effects of removal of dietary polyunsaturated fatty acids on plasma extravasation and mechanical allodynia in a trigeminal neuropathic pain model

<p>Abstract</p> <p>Background</p> <p>Neuropathic pain (NP) is partially mediated by neuroinflammatory mechanisms, and also modulates local neurogenic inflammation. Dietary lipids, in particular the total amount and relative proportions of polyunsaturated fatty acids (PUFAs) of the ω-3 and ω-6 families, have been reported to modify the threshold for thermal and mechanical allodynia in the partial sciatic nerve ligation model of NP in rats. The effects of dietary lipids on other popular NP models, such as the chronic constriction injury (CCI), have not yet been examined. It is also unknown whether dietary PUFAs exert any effect on the capsaicin (CAP)-induced neurogenic inflammation under control or NP conditions. In this study we investigated these interrelated phenomena in the trigeminal territory, which has been much less explored, and for which not all data derived from limb nerves can be directly applied.</p> <p>Results</p> <p>We studied the effects of a CCI of the infraorbital nerve (IoN) on the development of mechanical allodynia and CAP-induced plasma extravasation in rats fed either a regular diet (RD), or a modified diet (MD) with much lower total content and ω-3:ω-6 ratio of PUFAs. In rats kept on MD, mechanical allodynia following CCI-IoN was more pronounced and developed earlier. Extravasation was substantially increased in naive rats fed MD, and displayed differential diet-depending changes one and four weeks after CCI-IoN. When compared with basal levels (in naive and/or sham cases), the net effect of CCI-IoN on ipsilateral extravasation was a reduction in the MD group, but an increase in the RD group, effectively neutralizing the original intergroup differences.</p> <p>Conclusion</p> <p>In summary, PUFA intake reduces CAP-induced neurogenic plasma extravasation in the trigeminal territory, and their removal significantly alters the mechanical allodynia and the plasma extravasation that result from a unilateral CCI-IoN. It is likely that this "protective" effect of dietary lipids is temporary. Also, the presence of contralateral effects of CCI-IoN precludes using the contralateral side as control.</p

Elevated antibody to D-alanyl lipoteichoic acid indicates caries experience associated with fluoride and gingival health

BACKGROUND: Acidogenic, acid-tolerant bacteria induce dental caries and require D-alanyl glycerol lipoteichoic acid (D-alanyl LTA) on their cell surface. Because fluoride inhibits acid-mediated enamel demineralization, an elevated antibody response to D-alanyl LTA may indicate subjects with more acidogenic bacteria and, therefore, an association of DMFT with fluoride exposure and gingival health not apparent in low responders. METHODS: Cluster analysis was used to identify low antibody content. Within low and high responders (control and test subjects), the number of teeth that were decayed missing and filled (DMFT), or decayed only (DT) were regressed against fluoride exposure in the water supply and from dentrifice use. The latter was determined from gingival health: prevalences of plaque (PL) and bleeding on probing (BOP), and mean pocket depth (PD). Age was measured as a possible confounding cofactor. RESULTS: In 35 high responders, DMFT associated with length of exposure to fluoridated water (F score), PL and BOP (R(2) = 0.51, p < 0.001), whereas in 67 low D-ala-IgG responders, DMFT associated with PL, age, and PD (R(2) = 0.26, p < 0.001). BOP correlated strongly with number of 7 7 decayed teeth (DT) in 54 high responders (R(2) = 0.57, p < 0.001), but poorly in 97 low responders (R(2) = 0.12, p < 0.001). The strength of the PD association with DMFT, or of BOP with DT, in high responders significantly differed from that in low responders (p < 0.05). CONCLUSION: Caries associates with gingival health and fluoridated water exposure in high D-alanyl LTA antibody responders

Scope and Impact of International Research in Human Pluripotent Stem Cells

In a recent study published in this journal it was claimed that the rate of publications from US-based authors in the human embryonic stem cell (hESC) research field was slowing or even declining from 2008 to 2010. It was assumed that this is the result of long-term effects of the Bush administration’s funding policy for hESC research and the uncertain policy environment of recent years. In the present study, we analyzed a pool of more than 1,700 original hESC research papers published world-wide from 2007 to 2011. In contrast to the previous study, our results do not support the hypothesis of a decline in the productivity of US-based research but rather confirm a nearly unchanged leading position of US research in the hESC field with respect to both publication numbers and impact of research. Moreover, we analyzed about 500 papers reporting original research involving human induced pluripotent stem cells (hiPSCs) published through 2011 and found a dominant position of US research in this research field as well. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12015-012-9409-0) contains supplementary material, which is available to authorized users

Mesenchymal stromal-cell transplants induce oligodendrocyte progenitor migration and remyelination in a chronic demyelination model.

Demyelinating disorders such as leukodystrophies and multiple sclerosis are neurodegenerative diseases characterized by the progressive loss of myelin that may lead toward a chronic demyelination of the brain¿s white matter, impairing normal axonal conduction velocity and ultimately causing neurodegeneration. Current treatments modifying the pathological mechanisms are capable of ameliorating the disease; however, frequently, these therapies are not sufficient to repress the progressive demyelination into a chronic condition and permanent loss of function. To this end, we analyzed the effect that bone marrowderived mesenchymal stromal cell (BM-MSC) grafts exert in a chronically demyelinated mouse brain. As a result, oligodendrocyte progenitors were recruited surrounding the graft due to the expression of various trophic signals by the grafted MSCs. Although there was no significant reaction in the non-grafted side, in the grafted regions oligodendrocyte progenitors were detected. These progenitors were derived from the nearby tissue as well as from the neurogenic niches, including the subependymal zone and dentate gyrus. Once near the graft site, the cells matured to myelinating oligodendrocytes. Finally, electrophysiological studies demonstrated that axonal conduction velocity was significantly increased in the grafted side of the fimbria. In conclusion, we demonstrate here that in chronic demyelinated white matter, BM-MSC transplantation activates oligodendrocyte progenitors and induces remyelination in the tissue surrounding the stem cell graft

Management of orthodontic emergencies in primary care – self-reported confidence of general dental practitioners

Objective: To determine general dental practitioners’ (GDPs) confidence in managing orthodontic emergencies. Design: Cross-sectional study. Setting: Primary dental care. Subjects and methods: An online survey was distributed to dentists practicing in Wales. The survey collected basic demographic information and included descriptions of ten common orthodontic emergency scenarios. Main outcome measure Respondents’ self-reported confidence in managing the orthodontic emergency scenarios on a 5‑point Likert scale. Differences between the Likert responses and the demographic variables were investigated using chi-squared tests. Results: The median number of orthodontic emergencies encountered by respondents over the previous six months was 1. Overall, the self-reported confidence of respondents was high with 7 of the 10 scenarios presented scoring a median of 4 indicating that GDPs were ‘confident’ in their management. Statistical analysis revealed that GDPs who saw more orthodontic emergencies in the previous six months were more confident when managing the presented scenarios. Other variables such as age, gender, geographic location of practice and number of years practising dentistry were not associated with self reported confidence. Conclusions: Despite GDPs encountering very few orthodontic emergencies in primary care, they appear to be confident in dealing with commonly arising orthodontic emergency situations

HSP60 as a Target of Anti-Ergotypic Regulatory T Cells

The 60 kDa heat shock protein (HSP60) has been reported to influence T-cell responses in two ways: as a ligand of toll-like receptor 2 signalling and as an antigen. Here we describe a new mechanism of T-cell immuno-regulation focused on HSP60: HSP60 is up-regulated and presented by activated T cells (HSP60 is an ergotope) to regulatory (anti-ergotypic) T cells. Presentation of HSP60 by activated T cells was found to be MHC-restricted and dependent on accessory molecules - CD28, CD80 and CD86. Anti-ergotypic T cells responded to T-cell HSP60 by proliferation and secreted IFNγ and TGFβ1. In vitro, the anti-ergotypic T cells inhibited IFNγ production by their activated T-cell targets. In vivo, adoptive transfer of an anti-ergotypic HSP60-specific T-cell line led to decreased secretion of IFNγ by arthritogenic T cells and ameliorated adjuvant arthritis (AA). Thus, the presentation of HSP60 by activated T cells turns them into targets for anti-ergotypic regulatory T cells specific for HSP60. However, the direct interaction between the anti-ergotypic T regulators (anti-HSP60) and the activated T cells also down-regulated the regulators. Thus, by functioning as an ergotope, HSP60 can control both the effector T cells and the regulatory HSP60-specific T cells that control them

A polymorphism at codon 31 of gene p21 is not associated with primary open angle glaucoma in Caucasians

BACKGROUND: Primary open angle glaucoma (POAG) is considered to be a neurodegenerative optic neuropathy, in which cell death occurs by apoptosis. p21, is an important protective component of the apoptotic pathway, regulating cellular arrest in the presence of DNA damage. An unstable or altered p21 protein could modify the cellular response to genomic injury and abolish the effect of p21. A previous study on a Chinese cohort suggested that the p21 codon 31 polymorphism may alter the state of apoptosis in glaucomatous optic neuropathy, failing to protect the ganglion cells. The aim of this study was to test the hypothesis that a p21 codon 31 polymorphism is associated with POAG on a Caucasian cohort. METHODS: 140 POAG patients and a control group of 73 healthy individuals were included in the study. All the subjects were of Caucasian origin. Genomic DNA was amplified by polymerase chain reaction, followed by enzymatic restriction fragment length polymorphism technique (PCR-RFLP). Patients and controls were genotyped for a single nucleotide polymorphism (C/A transversion) in the third base of codon 31 of p21, which leads to a serine (Ser)/arginine (Arg) substitution. RESULTS: The distribution of the genotypes in the POAG patients showed 128 (91.4%) Ser homozygotes, 10 (7.1%) Ser/Arg heterozygotes and 2 (1.5%) Arg homozygotes. In the control cohort, there were 61 (83.6%) Ser homozygotes and 12 (16.4%) Ser/Arg heterozygotes. No Arg homozygotes were present amongst the control group. Both the allelic and genotypic frequencies of the Ser or Arg residues at codon 31 were not significantly different between POAG patients and controls (Fisher's exact test, P = 0.20 for alleles and P = 0.0561 for genotypes). CONCLUSION: This study suggests that the p21 codon 31 polymorphism does not contribute to the risk of POAG in the Caucasian population

Prioritising surveillance for alien organisms transported as stowaways on ships travelling to South Africa

The global shipping network facilitates the transportation and introduction of marine and terrestrial organisms to regions where they are not native, and some of these organisms become invasive. South Africa was used as a case study to evaluate the potential for shipping to contribute to the introduction and establishment of marine and terrestrial alien species (i.e. establishment debt) and to assess how this varies across shipping routes and seasons. As a proxy for the number of species introduced (i.e. 'colonisation pressure') shipping movement data were used to determine, for each season, the number of ships that visited South African ports from foreign ports and the number of days travelled between ports. Seasonal marine and terrestrial environmental similarity between South African and foreign ports was then used to estimate the likelihood that introduced species would establish. These data were used to determine the seasonal relative contribution of shipping routes to South Africa's marine and terrestrial establishment debt. Additionally, distribution data were used to identify marine and terrestrial species that are known to be invasive elsewhere and which might be introduced to each South African port through shipping routes that have a high relative contribution to establishment debt. Shipping routes from Asian ports, especially Singapore, have a particularly high relative contribution to South Africa's establishment debt, while among South African ports, Durban has the highest risk of being invaded. There was seasonal variation in the shipping routes that have a high relative contribution to the establishment debt of the South African ports. The presented method provides a simple way to prioritise surveillance effort and our results indicate that, for South Africa, port-specific prevention strategies should be developed, a large portion of the available resources should be allocated to Durban, and seasonal variations and their consequences for prevention strategies should be explored further. (Résumé d'auteur

The development and piloting of the graduate assessment of preparedness for practice (GAPP) questionnaire

Introduction Most new dental graduates in the UK begin their professional career following a year in dental foundation training (DFT). There has been little investigation of how prepared they feel for independent general dental practice across all four domains of the General Dental Council’s curriculum ‘Preparing for practice’. This paper describes the development of the Graduate Assessment of Preparedness for Practice (GAPP) questionnaire to address this. Methodology The GAPP questionnaire was developed and piloted using a cohort of educational supervisors (ESs) and foundation dentists (FDs). The questionnaire comprised three parts, the first of which collected respondent demographic data. The second was based on Preparing for practice and was used to develop 34 ‘competence areas’ and required a tick-box response on a 7‑category Likert Scale. The third comprised free text questions in order to further explore the subject’s responses. Results Pilot feedback was positive, the statements were felt to be clear and unambiguous, allowing them sufficient scope to state their position. The pilot study informed small cosmetic changes to the GAPP questionnaire and inclusion of a ‘comments’ column for respondents to qualify their responses. The pilot results indicated that both FDs and their ESs felt that at ten months of DFT, the FDs were very well prepared for independent general dental practice. Discussion The paper describes the important considerations relating to the reliability and validity of the GAPP questionnaire. Conclusions GAPP appears to be a suitable questionnaire to measure preparedness of new graduates with a degree of reliability and validity. The instrument is designed to be simple to complete and provides a useful analytical instrument for both self-assessment of competence and for wider use within dental education