bluuebunny/crossref_metadata_2025 huggingface dataset:
Translational Mini-Review Series on Th17 Cells: Induction of interleukin-17 production by regulatory T cells
Authors: Afzali B , Mitchell P , Lechler R I , John S , Lombardi G
Published: November 2009

OTHER ARTICLES PUBLISHED IN THIS MINI-REVIEW SERIES ON Th17 CELLS Function and regulation of human T helper 17 cells in health and disease. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04037.x Are T helper 17 cells really pathogenic in autoimmunity? Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04039.x CD4+ T helper cells: functional plasticity and differential sensitivity to regulatory T cell-mediated regulation. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04040.x Development of mouse and human T helper 17 cells. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04041.x

Uncommitted (naive) CD4+ T helper cells (Thp) can be induced to differentiate to specific lineages according to the local cytokine milieu, towards T helper type 1 (Th1), Th2, Th17 and regulatory T cell (Treg) phenotypes in a mutually exclusive manner. Each phenotype is characterized by unique signalling pathways and expression of specific transcription factors, notably T-bet for Th1, GATA-3 for Th2, forkhead box P3 (FoxP3) for Tregs and receptor-related orphan receptor (ROR)α and RORγt for Th17 cells. Tregs and Th17 cells have been demonstrated to arise from common precursors in a reciprocal manner based on exposure to transforming growth factor (TGF)-β or TGF-β plus interleukin (IL)-6 and carry out diametrically opposing functions, namely suppression or propagation of inflammation, respectively. However, while epigenetic modifications in Th1 and Th2 differentiated cells prevents their conversion to other phenotypes, Th17 cells generated in vitro using TGF-β and IL-6 are unstable and can convert to other phenotypes, especially Th1, both in vitro and in vivo. Tregs are generated from naive precursors both in the thymus (natural, nTregs) and in the periphery (induced, iTregs). The highly suppressive function of Tregs enables them to control many inflammatory diseases in animals and makes them particularly attractive candidates for immunotherapy in humans. The stability of the Treg phenotype is therefore of paramount importance in this context. Recent descriptions of Treg biology have suggested that components of pathogens or inflammatory mediators may subvert the suppressive function of Tregs in order to allow propagation of adequate immune responses. Unexpectedly, however, a number of groups have now described conversion of Tregs to the Th17 phenotype induced by appropriate inflammatory stimuli. These observations are particularly relevant in the context of cell therapy but may also explain some of the dysregulation seen in autoimmune diseases. In this paper, we review Treg to Th17 conversion and propose some potential mechanisms for this phenomenon.
Translational Mini-Review Series on Th17 Cells: Are T helper 17 cells really pathogenic in autoimmunity?
Authors: Koenders M I , Van Den Berg W B
Published: November 2009

OTHER ARTICLES PUBLISHED IN THIS MINI-REVIEW SERIES ON Th17 CELLS Function and regulation of human T helper 17 cells in health and disease. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04037.x Induction of interleukin-17 production by regulatory T cells. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04038.x CD4+ T helper cells: functional plasticity and differential sensitivity to regulatory T cell-mediated regulation. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04040.x Development of mouse and human T helper 17 cells. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04041.x

In this review the authors discuss the evidence for T helper type 17 (Th17) cells as pathogenic T cells in autoimmunity. Studies with cytokine-deficient mice or blocking of interleukin (IL)-17, IL-21 and IL-22 have resulted in a conflicting data set. Although in the experimental autoimmune encephalomyelitis model the role of Th17 cells remains a point of debate, this IL-17-producing T cell in experimental arthritis is clearly contributing to inflammation and destruction.
Translational Mini-Review Series on Th17 Cells: CD4+ T helper cells: functional plasticity and differential sensitivity to regulatory T cell-mediated regulation
Authors: O'Connor R A , Taams L S , Anderton S M
Published: November 2009

OTHER ARTICLES PUBLISHED IN THIS MINI-REVIEW SERIES ON Th17 CELLS Function and regulation of human T helper 17 cells in health and disease. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04037.x Induction of interleukin-17 production by regulatory T cells. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04038.x Are T helper 17 cells really pathogenic in autoimmunity? Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04039.x Development of mouse and human T helper 17 cells. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04041.x

CD4+ T cells display considerable flexibility in their effector functions, allowing them to tackle most effectively the range of pathogenic infections with which we are challenged. The classical T helper (Th) 1 and Th2 subsets have been joined recently by the Th17 lineage. If not controlled, the potent effector functions (chiefly cytokine production) of which these different cells are capable can lead to (sometimes fatal) autoimmune and allergic inflammation. The primary cell population tasked with providing this control appears to be CD4+ regulatory T (Treg) cells expressing the forkhead box P3 (FoxP3) transcription factor. Here we consider the comparative capacity of FoxP3+ Tregs to influence the polarization, expansion and effector function of Th1, Th2 and Th17 cells in vitro and in vivo as well as in relation to human disease. This remains a particularly challenging series of interactions to understand, especially given our evolving understanding of Treg and T effector interrelationships, as well as recent insights into functional plasticity that cast doubt upon the wisdom of a strict categorization of T effector cells based on cytokine production.
Translational Mini-Review Series on Th17 Cells: Development of mouse and human T helper 17 cells
Authors: De Jong E , Suddason T , Lord G M
Published: November 2009

OTHER ARTICLES PUBLISHED IN THIS MINI-REVIEW SERIES ON Th17 CELLS Function and regulation of human T helper 17 cells in health and disease. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04037.x Induction of interleukin-17 production by regulatory T cells. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04038.x Are T helper 17 cells really pathogenic in autoimmunity? Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04039.x CD4+ T helper cells: functional plasticity and differential sensitivity to regulatory T cell-mediated regulation. Clin Exp Immunol 2009; doi:10.1111/j.1365-2249.2009.04040.x

There has been a considerable amount of interest in the immunological community about new phenotypic subsets of CD4+ T cells, particularly cells that produce the cytokine interleukin (IL)-17 [named T helper type 17 (Th17) cells]. While the initial discovery of Th17 cells and the pathways that controlled their development was in the mouse, recent attention has shifted to the existence of these cells and the relevant upstream cytokine signals in humans. While it is clear that CD4+ T cells producing IL-17 exist in vivo, their relevance to disease pathogenesis is only just being understood. In this paper, we review the data regarding the generation of human Th17 cells in vitro and the evidence that this effector population is important in human disease states.
Recipient NOD2/CARD15 status affects cellular infiltrates in human intestinal graft-versus-host disease
Authors: Landfried K , Bataille F , Rogler G , Brenmoehl J , Kosovac K , Wolff D , Hilgendorf I , Hahn J , Edinger M , Hoffmann P , Obermeier F , Schoelmerich J , Andreesen R , Holler E
Published: November 2009

Nucleotide-binding oligomerization domain 2/caspase recruitment domain 15 (NOD2/CARD15) polymorphisms have been identified as risk factors of both Crohn's disease and graft-versus-host disease (GVHD) following allogeneic stem cell transplantation. However, the role of these receptors of innate immunity in the pathophysiology of gastrointestinal GVHD is still poorly defined. Immunohistological features of intestinal GVHD were analysed in gastrointestinal biopsies from 58 patients obtained at the time of first onset of intestinal symptoms. The observed changes were correlated with concomitant risk factors and the presence of polymorphisms within the pathogen recognition receptor gene NOD2/CARD15. Intestinal GVHD was associated with a stage-dependent decrease in CD4 T cell infiltrates and an increase in CD8 T cells in the lamina propria; CD8 infiltrates correlated with extent of apoptosis and consecutive epithelial proliferation. The presence of NOD2/CARD15 variants in the recipient was associated with a significant loss of CD4 T cells: in a semiquantitative analysis, the median CD4 score for patients with wild-type NOD2/CARD15 was 1·1 (range 3), but only 0·4 (range 2) for patients with variants (P = 0·002). This observation was independent from severity of GVHD in multivariate analyses and could not be explained by the loss of forkhead box P3+ T cells. Our results suggest a loss of protective CD4 T cells in intestinal GVHD which is enhanced further by the presence of NOD2/CARD15 variants. Our study might help to identify more selective therapeutic strategies in the future.
Gene expression profiles for the human pancreas and purified islets in Type 1 diabetes: new findings at clinical onset and in long-standing diabetes
Authors: Planas R , Carrillo J , Sanchez A , Ruiz de Villa M C , Nuñez F , Verdaguer J , James R F L , Pujol-Borrell R , Vives-Pi M
Published: November 2009

Type 1 diabetes (T1D) is caused by the selective destruction of the insulin-producing β cells of the pancreas by an autoimmune response. Due to ethical and practical difficulties, the features of the destructive process are known from a small number of observations, and transcriptomic data are remarkably missing. Here we report whole genome transcript analysis validated by quantitative reverse transcription–polymerase chain reaction (qRT–PCR) and correlated with immunohistological observations for four T1D pancreases (collected 5 days, 9 months, 8 and 10 years after diagnosis) and for purified islets from two of them. Collectively, the expression profile of immune response and inflammatory genes confirmed the current views on the immunopathogenesis of diabetes and showed similarities with other autoimmune diseases; for example, an interferon signature was detected. The data also supported the concept that the autoimmune process is maintained and balanced partially by regeneration and regulatory pathway activation, e.g. non-classical class I human leucocyte antigen and leucocyte immunoglobulin-like receptor, subfamily B1 (LILRB1). Changes in gene expression in islets were confined mainly to endocrine and neural genes, some of which are T1D autoantigens. By contrast, these islets showed only a few overexpressed immune system genes, among which bioinformatic analysis pointed to chemokine (C-C motif) receptor 5 (CCR5) and chemokine (CXC motif) receptor 4) (CXCR4) chemokine pathway activation. Remarkably, the expression of genes of innate immunity, complement, chemokines, immunoglobulin and regeneration genes was maintained or even increased in the long-standing cases. Transcriptomic data favour the view that T1D is caused by a chronic inflammatory process with a strong participation of innate immunity that progresses in spite of the regulatory and regenerative mechanisms.
Serum insulin‐like growth factor‐I and body composition in community dwelling older people
Authors: Jakobsdóttir Sigridur , Caroline van Nieuwpoort I. , Schaap Laura A. , Van Schoor Natasja M. , Lips Paul , Drent Madeleine L.
Published: November 2009

Objectives The decline in the growth hormone/insulin‐like growth factor‐I (GH/IGF‐I) axis during normal aging might be involved in the changes in body composition associated with increasing age. We conducted a study to investigate serum IGF‐I levels across different age categories and a possible association between serum IGF‐I and measurements of body composition in older people.

Design A cross‐sectional analysis of community dwelling older people, which participated in a large longitudinal cohort study (Longitudinal Aging Study Amsterdam).

Subjects 1319 subjects, 644 men, mean age 75·6 ± 6·6 years and 675 women, mean age 75·4 ± 6·6 years.

Main Outcome Measurements IGF‐I, body mass index (BMI), waist, waist‐hip ratio (WHR), fat mass, lean body mass and total bone mineral density.

Results IGF‐I levels were significantly lower in the highest age categories. BMI and biceps skinfold measurements were lower in the lowest IGF‐I quartile in men aged ≥75·5 years. In men with a low total physical activity score (<131 min/day), BMI, WHR and skinfolds were significantly lower in the lowest IGF‐I quartile. In women with a high total physical activity score (>174 min/day), WHR was lower in the lowest IGF‐I quartiles.

Conclusion In this large cohort of community dwelling older people, we observed lower serum IGF‐I levels in the higher age categories. A low serum IGF‐I was associated with significantly lower measurements of body composition, such as BMI, skinfolds and WHR. These results do not support previous findings that high IGF‐I levels are favourable for a healthy body composition in community dwelling older people.
Characterization of thyroglobulin epitopes in Sardinian adults and juveniles with Hashimoto’s thyroiditis: evidence against a major effect of age and genetic background on B‐cell epitopes
Authors: Latrofa Francesco , Ricci Debora , Vitti Paolo , Prinzis Alessia , Cambuli Valentina Maria , Ghiani Mariangela , Pilia Sabrina , Carta Daniela , Loche Sandro , Pinchera Aldo , Mariotti Stefano
Published: November 2009

Background  Using recombinant human monoclonal thyroglobulin antibodies expressed as Fab molecules (TgAb‐Fab), we have recently confirmed the restriction of Tg epitopes in Hashimoto’s thyroiditis (HT).

Objective  To investigate Tg epitopes of serum TgAb in HT adults and HT juveniles from a geographically isolated area (Sardinia).

Design and Patients  Serum TgAb of 39 Sardinian HT adults, 53 Sardinian HT juveniles and 45 non‐Sardinian HT adults were evaluated. The binding of serum TgAb to Tg in ELISA was inhibited by four recombinant human TgAb‐Fab, identifying Tg epitopic regions A–D. The percentage of Tg binding inhibition was calculated comparing the binding of serum TgAb in presence of each TgAb‐Fab with that in its absence.

Results  In the whole cohort of 137 patients, A region TgAb‐Fab induced the highest levels of inhibition (55·3 ± 17·8%) (mean ± SD). Lower levels of inhibition were induced by TgAb‐Fab of regions B (27·8 ± 25·8%), C (26·8 ± 24·6%) and D (17·5 ± 18·4%). In Sardinian HT adults inhibition by TgAb‐Fab of regions A, B and C were comparable to Sardinian HT juveniles; the marginal D region TgAb‐Fab induced a slightly higher inhibition (22·1 vs. 13·8%; P = 0·034) in the former than in the latter group. In Sardinian and non‐Sardinian HT adults inhibitions by the four TgAb‐Fab were similar.

Conclusions  In HT, the Tg epitope pattern of serum TgAb was similar in juveniles and adults from a geographically restricted area and in two adult populations from different geographical areas. Thus, in HT, neither age nor genetic background appear to influence B‐cell epitopes.
Urinary L‐FABP and anaemia: distinct roles of urinary markers in type 2 diabetes
Authors: Von Eynatten M. , Baumann M. , Heemann U. , Zdunek D. , Hess G. , Nawroth P. P. , Bierhaus A. , Humpert P. M.
Published: November 2009

Eur J Clin Invest 2010; 40 (2): 95–102

Background  Urinary liver‐type fatty acid binding protein (L‐FABP) and kidney injury molecule (KIM)‐1, novel urinary biomarkers of renal tubulointerstitial function, have previously been associated with acute ischaemic kidney injury. We studied the clinical significance of urinary L‐FABP, KIM‐1 and N‐acetyl‐β‐glucosaminidase (NAG) as potential markers of renal function and chronic ischaemic injury in patients with diabetic nephropathy.

Material and methods  A total of 130 type 2 diabetes patients with early diabetic nephropathy and 40 healthy controls were studied. Urinary L‐FABP, KIM‐1, NAG, albumin excretion rate (AER) and creatinine clearance were obtained from 24‐h urine samples, and correlated with measures of red blood cell count, renal function and metabolic control.

Results  Urinary L‐FABP was significantly increased in diabetes patients compared with healthy controls [8·1 (interquartile 0·6–11·6) vs. 2·4 (0·5–3·6) μg/g creatinine, P < 0·001] and correlated with AER (r = 0·276, P = 0·002), creatinine clearance (r = −0·189, P = 0·033) and haemoglobin levels (r = −0·190, P = 0·030). In multivariable linear regression analysis, haemoglobin (β = −0·247, P = 0·015) and AER (β = 0·198, P = 0·046) were significant predictors of urinary L‐FABP. Prevalent anaemia was independently associated with a 6‐fold risk for increased tubulointerstitial kidney damage (upper vs. lower two L‐FABP tertiles: OR, 6·06; 95% CI: 1·65–22·23; P = 0·007). Urinary KIM‐1 was not significantly associated with kidney function, AER, or measures of red blood cell count while urinary NAG was associated with parameters of glucose control and renal function.

Conclusions  Different urinary biomarkers may reflect distinct pathophysiological mechanisms of tubulointerstitial damage in early diabetic nephropathy: Urinary L‐FABP could be a novel biomarker for chronic intrarenal ischaemia.
Malignancy in patients with haemophilia: a review of the literature
Authors: DUNN A. L.
Published: November 2009

Summary.  Haemophilia A and B are rare X‐linked conditions. Elevated rates of HIV and hepatitis C related malignancies in these patients are well reported, however rates of other types of cancers are not. Therefore, a retrospective literature review of cancer in patients with haemophilia was conducted. A Medline search of articles from January 1966 to July 2009 utilizing the keywords haemophilia, leukaemia, malignancy, mortality, neoplasm and cancer was performed. The articles were reviewed and additional relevant publications were located from the references. Data on age, type and severity of haemophilia, HIV status, type of malignancy and outcomes were recorded as available. Thirty‐two cases of leukaemia were identified as well as 159 malignant solid tumours. Specific incidence and prevalence rates could not be calculated due to the limited nature of the information available in the reports. Many types of malignancy have been reported in persons with haemophilia irrespective of infection with HIV and hepatitis C yet prevalence and incidence rates compared to the general population remain unknown. Patients with haemophilia can manifest non infectious related malignancies and symptomatic patients should be evaluated accordingly.
Purification and characterization of a new recombinant factor VIII (N8)
Authors: THIM L. , VANDAHL B. , KARLSSON J. , KLAUSEN N. K. , PEDERSEN J. , KROGH T. N. , KJALKE M. , PETERSEN J. M. , JOHNSEN L. B. , BOLT G. , NØRBY P. L. , STEENSTRUP T. D.
Published: November 2009

Summary.  A new recombinant factor VIII (FVIII), N8, has been produced in Chinese hamster ovary (CHO) cells. The molecule consists of a heavy chain of 88 kDa including a 21 amino acid residue truncated B‐domain and a light chain of 79 kDa. The two chains are held together by non‐covalent interactions. The four‐step purification includes capture, affinity purification using a monoclonal recombinant antibody, anion exchange chromatography and gel filtration. The specific clotting activity of N8 was 8800–9800 IU mg−1. Sequence and mass spectrometry analysis revealed two variants of the light chain, corresponding to two alternative N‐terminal sequences also known from plasma FVIII. Two variants of the heavy chain are present in the purified product, namely with and without the B‐domain linker attached. This linker is removed upon thrombin activation of N8 rendering an activated FVIII (FVIIIa) molecule similar to plasma FVIIIa. All six known tyrosine sulphations of FVIII were confirmed in N8. Two N‐linked glycosylations are present in the A3 and C1 domain of the light chain and two in the A1 domain of the heavy chain. The majority of the N‐linked glycans are sialylated bi‐antennary structures. An O‐glycosylation site is present in the B‐domain linker region. This site was glycosylated with a doubly sialylated GalNAc‐Gal structure in approximately 65% of the product. In conclusion, the present data show that N8 is a pure and well‐characterized FVIII product with biochemical properties that equal other FVIII products.
Development and preliminary testing of a Paediatric Version of the Haemophilia Activities List (pedhal)
Authors: GROEN W. G. , Van Der NET J. , HELDERS P. J. M. , FISCHER K.
Published: November 2009

Summary.  Worldwide, children with haemophilia suffer from limitations in performing activities of daily living. To measure such limitations in adults a disease‐specific instrument, the Haemophilia Activities List (HAL), was created in 2004. The aim of this study was to adapt the HAL for children with haemophilia and to assess its psychometric properties. The structure and the main content were derived from the HAL. Additionally, items of the Childhood Health Assessment Questionnaire and the Activity Scale for Kids were considered for inclusion. This version was evaluated by health professionals (n = 6), patients (n = 4), and parents (n = 3). A pilot test in a sample of 32 Dutch children was performed to assess score distribution, construct validity (Spearman’s rho) and reproducibility. Administration of the pedhal was feasible for children from the age of 4 years onwards. The pedhal scores of the Dutch children were in the high end of the scale, reflecting a good functional status. Most subscales showed moderate associations with the joint examination (rho = 0.42–0.63) and moderate‐to‐good associations with the physical function subscale of the CHQ‐50 (rho = 0.48–0.74). No significant associations were found for the pedhal and the subscales mental health and behaviour, except for the subscales leisure and sport and mental health (rho = 0.47). Test–retest agreement was good. The pedhal is a promising tool, but further testing in populations with a higher level of disability is warranted to study the full range of its psychometric properties.
A micro‐computed tomographic evaluation of apical root canal preparation using three instrumentation techniques
Authors: Moore J. , Fitz‐Walter P. , Parashos P.
Published: November 2009

Aim  To investigate the morphological changes in the apical third of the root canal after preparation with three techniques.

Methodology  Forty molar teeth were scanned using micro‐computed tomography before and after instrumentation with: Group 1 – stainless steel K‐files using the balanced force technique; Group 2 – stainless steel K‐files (balanced force) and then refining the apical preparation with the equivalent size 0.04 taper FlexMaster instrument; Group 3 – a hybrid ProTaper/FlexMaster (ProFile for sizes 45 and 60) sequence. Eight canals were excluded because of artefacts in the images or unnegotiable blockages leaving 110 canals that could be analysed. Apical root canal preparation was evaluated with respect to the amount of dentine removed, canal roundness, transportation and how the dimensions of the prepared apical root canal correlated with those of the final instrument used.

Results  The median apical preparation sizes for the three groups respectively were: 30, 30 and 40. Despite the larger size and less experienced operator, the volumetric change (the amount of dentine removed) in canals prepared with a hybrid rotary nickel–titanium instrumentation technique remained small and, a more rounded preparation (P < 0.001) that closely matched the final instrument dimensions (P < 0.001) was produced. There was a trend for less canal transportation using rotary nickel–titanium instruments.

Conclusions  Stainless steel hand preparation was not conservative of apical dentine. When used correctly, even by less experienced operators, rotary nickel–titanium instruments were able to precisely ‘machine’ a canal to larger apical sizes with minimal risk of iatrogenic damage.
Distance from file tip to the major apical foramen in relation to the numeric meter reading on the display of three different electronic apex locators
Authors: Higa R. A. , Adorno C. G. , Ebrahim A. K. , Suda H.
Published: November 2009

Aim  To establish and compare the relationship between the distance from the file tip to the apical foramen and the numeric meter reading on the display of three different electronic apex locators (EALs).

Methodology  A total of 12 extracted intact, straight, single‐rooted human teeth with complete roots were used. The actual root canal length (AL) was determined after access preparation. For the electronic measurements with each EAL, silicon stops were fixed with auto‐polymerizing resin to size 15 K‐files at AL and 0.5, 1, 2, 3, 4 mm short of AL. The data was analysed by two‐way anova and Tukey’s honestly significant difference (HSD) test for multiple comparisons amongst EALs. Additionally, one‐way anova and Tukey’s HSD test were carried out for multiple comparisons amongst the measurements of each EAL.

Results  There was a statistically significant difference amongst all EALs in indicating the position of file tips in relation to the major foramen (P < 0.05). The correlation between the meter reading and the position of the file tip from the apical foramen was statistically significant in the three EALs. There were significant differences amongst the measurements at distances from 0 to 2 mm in Justy III. In Dentaport, significant differences were found from 0 to 1 mm. However, the E‐Magic Finder showed significant differences from 0 to 0.5 mm.

Conclusions  Justy III was more capable of displaying the intracanal position of the file tip from the major foramen in mm whilst advancing through the root canal during electronic measurements than the Dentaport and E‐Magic Finder Deluxe.
Micro‐computed tomography of tooth tissue volume changes following endodontic procedures and post space preparation
Authors: Ikram O. H. , Patel S. , Sauro S. , Mannocci F.
Published: November 2009

Aim  To compare the volume of hard tooth tissue lost after caries removal, access cavity preparation, root canal preparation, fibre post space and cast post preparation in carious premolar teeth. The null hypothesis tested was that there is no difference between the volumes of hard tooth tissue lost expressed as a percentage of the preoperative hard tooth tissue volume, after each operative procedure.

Methodology  Twelve extracted human premolars with mesial or distal carious cavities penetrating into the pulp chamber were selected. Teeth were scanned using a microCT scanner. After each operative procedure the loss of hard tooth tissue volume was measured. The data were statistically analysed using one‐way analysis of variance and Fisher’s PLSD test with statistical significance set at α = 0.01.

Results  The percentage of preoperative hard tooth tissue volume lost after caries removal was 8.3 ± 5.83, after access cavity preparation the loss of volume reached 12.7 ± 6.7% (increase of 4.4%). After root canal preparation, fibre post space and cast post preparation the hard tissue volume lost reached, 13.7 ± 6.7 (increase of 1%), 15.1 ± 6.3 (increase of 1.4%) and 19.2 ± 7.4 (increase of 4.1%) respectively. Each procedure performed after caries removal significantly increased (P < 0.01) the amount of hard tissue volume lost with the exception of the root canal preparation.

Conclusions  Access cavity and post space preparation are the procedures during root canal treatment which result in the largest loss of hard tooth tissue structure. Cast post space preparation causes a larger loss of tooth structure than fibre post space preparation. This should be taken into account when planning root canal treatment and restoration of root filled teeth that are to be restored with cuspal coverage restorations.
One step pulp revascularization treatment of an immature permanent tooth with chronic apical abscess: a case report
Authors: Shin S. Y. , Albert J. S. , Mortman R. E.
Published: November 2009

Aim  To describe a case in which a mandibular right second premolar with a necrotic pulp, sinus tract, periradicular radiolucency and an immature apex underwent revascularization via a single treatment approach.

Summary  Revascularization procedures have the potential to heal a partially necrotic pulp, which can be beneficial for the continued root development of immature teeth. However, it is not clear which revascularization protocols are the most effective. This case report details the outcome of a successful revascularization procedure on tooth 45 (FDI) in a 12‐year‐old patient, eliminating the associated periapical pathosis within 19 months. The tooth was treated using coronal root irrigation with 6% NaOCl and 2% chlorhexidine without instrumentation in a single visit. The successful outcome of this case report suggests that this conservative revascularization treatment approach can preserve the vitality of the dental pulp stem cells and create a suitable environment for pulp regeneration, resulting in the completion of root maturation.

Key learning points

The noninstrumentation procedure using 6% NaOCl and 2% chlorhexidine coronal irrigation may help preserve the remaining vital dental pulp stem cells believed to be critical for pulp revascularization.

A single visit pulp revascularization protocol can be a favourable treatment option for an immature permanent tooth with a partially necrotic pulp.
Laser‐activated irrigation within root canals: cleaning efficacy and flow visualization
Authors: De Groot S. D. , Verhaagen B. , Versluis M. , Wu M.‐K. , Wesselink P. R. , Van Der Sluis L. W. M.
Published: November 2009

Aim  To test ex vivo the efficiency of laser‐activated irrigation in removing dentine debris from the apical part of the root canal and to visualize in vitro the fluid dynamics during the activation of the irrigant by laser, using high‐speed imaging at a relevant timescale.

Methodology  Root canals with a standardized groove in one canal wall filled with dentine debris were irrigated with syringe irrigation, ultrasonically or laser‐activated irrigation (LAI) using 2% sodium hypochlorite as irrigant. The quantity of dentine debris after irrigation was determined. Visualization of the fluid dynamics during activation was achieved using a high‐speed camera and a glass model.

Results  Laser‐activated irrigation was significantly more effective in removing dentine debris from the apical part of the root canal than passive ultrasonic irrigation or hand irrigation when the irrigant was activated for 20 s.

Conclusions  The in vitro recordings suggest that streaming, caused by the collapse of the laser‐induced bubble, is the main cleaning mechanism of LAI.
Sealing properties of a new root canal sealer
Authors: Salz U. , Poppe D. , Sbicego S. , Roulet J.‐F.
Published: November 2009

Aim  To evaluate bacterial leakage of Apexit Plus, a new root canal sealer, in comparison with AH Plus.

Methodology  A total of 56 single‐rooted human teeth were randomly divided into two experimental groups of 16 roots and two control groups. Roots were filled by lateral condensation with Gutta‐percha and AH Plus or with Gutta‐percha and Apexit Plus. A split chamber microbial leakage model was used in which Streptococcus mutans placed in the upper chamber could reach the lower chamber only through the filled canal. Positive controls were filled only with Gutta‐percha and tested with bacteria, whereas negative controls were sealed with wax to test the seal between chambers. Additionally, film thickness, solubility and dimensional change were determined.

Results  All positive controls leaked within 24 h, whereas none of the negative controls leaked after 30 days. Apexit Plus had significant less bacterial leakage (log‐rank test, P < 0.0001) than AH Plus. AH Plus (0.3% solubility) showed a slightly lower solubility than Apexit Plus (0.5% solubility) but a larger film thickness (28 vs. 11 μm) according to ISO 6876:2001.

Conclusion  Apexit Plus had a better sealing ability in comparison with AH Plus.
A tactile method for canal length determination in teeth with open apices
Authors: ElAyouti A. , Dima E. , Löst C.
Published: November 2009

Aim  To present a tactile method for working length determination in teeth with open apices and to determine its accuracy and repeatability.

Methodology  Ninety teeth with 129 root canals were prepared to create open apices. The correct working length (CWL) for each canal was determined by introducing a file into the root canal until it was visible at the apex. Consequently, the tactile working length (TWL) was determined by the ‘Tactile Method’ using a K‐file that was bent at the tip. Two operators repeated the measurement once in each root canal. The accuracy of the TWL was determined by comparing the TWL with the CWL. The mean of the absolute differences and the corresponding 99% confidence interval (CI) were calculated. Both the repeatability and inter‐operator agreement of the tactile method were determined by performing paired analysis of the differences between repeated measurements and the two operators.

Results  Overall, 97% (CI: 91–99) of the TWL were within 0.5 mm from the CWL, the mean of absolute differences was 0.1 mm (CI: 0.1–0.2). The maximum difference between repeated measurements was 0.2 mm and between the two operators was 0.6 mm.

Conclusions  The tactile method may provide an accurate determination of canal length in teeth with open apices.
Preliminary study of the presence and association of bacteria and archaea in teeth with apical periodontitis
Authors: Jiang Y. T. , Xia W. W. , Li C. L. , Jiang W. , Liang J. P.
Published: November 2009

Aim  To investigate, by reverse transcription polymerase chain reaction (RT‐PCR), the presence and association of bacteria and archaea in primary and secondary root canal infections.

Methodology  A total of 77 root canal samples from 77 Chinese patients, 42 with necrotic pulp tissues (primary infection) and 35 with failed prior conventional root canal treatment (secondary infection), aseptically exposed at the first patient visit, were studied. Total RNA was isolated directly from each sample, and 16S rRNA gene‐based RT‐PCR assays were used to determine the presence of bacteria and archaea, respectively.

Results  Bacteria were detected in 39/42 (93%) of root canal samples from teeth with primary infections, and archaea in 16/42 (38%). In the cases diagnosed as secondary root‐infected canals, bacteria were detected in 30/35 (86%), whilst archaea were detected in 6/35 (17%) of cases. Amongst the canals, which were positive for bacteria, archaea were always found in combination with bacteria. The incidence of symptomatic cases positive for both bacteria and archaea (16/22, 73%) were significantly higher than those positive for bacteria alone (21/47, 45%) (P < 0.05).

Conclusions  This study confirms the presence of archaea in root canal infections and further implicates them in an association with clinical symptoms. The nature of this association requires further study.
Antibiotic prescribing in dental practice in Belgium
Authors: Mainjot A. , D’Hoore W. , Vanheusden A. , Van Nieuwenhuysen J.‐P.
Published: November 2009

Aim  To assess the types and frequency of antibiotic prescriptions by Belgian dentists, the indications for antibiotic prescription, and dentists’ knowledge about recommended practice in antibiotic use.

Methodology  In this cross‐sectional survey, dental practitioners were asked to record information about all antibiotics prescribed to their patients during a 2‐week period. The dental practitioners were also asked to complete a self‐administered questionnaire regarding demographic data, prescribing practices, and knowledge about antibiotic use. A random sample of 268 Belgian dentists participated in the survey.

Results  During the 2‐week period, 24 421 patient encounters were recorded; 1033 patients were prescribed an antibiotic (4.2%). The median number of prescriptions per dentist for the 2 weeks was 3. Broad spectrum antibiotics were most commonly prescribed: 82% of all prescriptions were for amoxycillin, amoxycillin‐clavulanic acid and clindamycin. Antibiotics were often prescribed in the absence of fever (92.2%) and without any local treatment (54.2%). The most frequent diagnosis for which antibiotics were prescribed was periapical abscess (51.9%). Antibiotics were prescribed to 63.3% of patients with periapical abscess and 4.3% of patients with pulpitis. Patterns of prescriptions were confirmed by the data from the self‐reported practice.

Conclusions  Discrepancies between observed and recommended practice support the need for educational initiatives to promote rational use of antibiotics in dentistry in Belgium.
P450‐aromatase activity and expression in human testicular tissues with severe spermatogenic failure
Authors: Lardone M. C. , Castillo P. , Valdevenito R. , Ebensperger M. , Ronco A. M. , Pommer R. , Piottante A. , Castro A.
Published: November 2009

There is evidence that impaired spermatogenesis is associated with an imbalance in the oestradiol/testosterone ratio and with Leydig cell (LC) dysfunction. In testis, P450‐aromatase, encoded by CYP19, is responsible for the conversion of testosterone to oestradiol. The aims of this study were to quantify CYP19 mRNA expression, aromatase activity and protein localization, and to measure the oestradiol to testosterone ratio in testicular tissues of men with spermatogenic impairment. Twenty‐four men with complete Sertoli cell‐only syndrome (SCOS), 14 with focal SCOS, 14 with maturation arrest (MA), 8 with mixed atrophy and 30 controls with normal spermatogenesis were subjected to testicular biopsy. All subjects underwent a physical examination, cytogenetic and serum hormonal studies. Testicular CYP19 mRNA was quantified using real time RT‐PCR. Testicular aromatase activity was measured using the 3H20 assay and protein expression was evaluated using immunohistochemistry. In cases, serum testosterone and oestradiol were normal, but the testosterone/LH ratio was lower compared with controls (p < 0.05). Aromatase was localized in the Leydig, Sertoli and germ cells of all tissues, although stronger intensity was observed in LC. Aromatase mRNA and activity were not altered in cases and correlated positively with LC number (r = 0.516 and r = 0.369; p < 0.008). The intratesticular oestradiol/testosterone ratio was elevated (p = 0.005) in complete SCOS patients compared with controls. In conclusion, testicular aromatase seems to be normal in most subjects with impaired spermatogenesis. However, an altered intratesticular oestradiol/testosterone ratio in some patients with complete SCOS suggests that aromatase is increased, which might contribute to Leydig cell dysfunction.
Stromal remodelling is required for progressive involution of the rat ventral prostate after castration: Identification of a matrix metalloproteinase‐dependent apoptotic wave
Authors: Bruni‐Cardoso A. , Augusto T. M. , Pravatta H. , Damas‐Souza D. M. , Carvalho H. F.
Published: November 2009

Prostate epithelial‐cell apoptosis occurs in response to androgen deprivation. We have hypothesized that continued regression would require stromal changes. Studying apoptosis kinetics up to the 14th day after castration, we identified successive waves of apoptosis, with a prominent peak on day 11. This peak was associated with caspase‐3 activity, nuclear translocation of apoptosis‐inducing factor and clusterin expression. The apoptosis peak on day 11 was preceded by increased MMP‐2 and MMP‐7 activation, and MMP‐9 expression on days 9 and 10. Treatment with the matrix metalloproteinases inhibitors doxycyclin, hydrocortisone, or GM6001 caused significant reduction in the apoptosis rate on day 11. The present data demonstrate that prostatic epithelial‐cell deletion at the 11th day after castration was induced by focal degradation of the extracellular matrix associated with stromal remodelling.
Proteome analysis and genome‐wide regulatory motif prediction identify novel potentially sex‐hormone regulated proteins in rat efferent ducts
Authors: Trépos‐Pouplard M. , Lardenois A. , Staub C. , Guitton N. , Dorval‐Coiffec I. , Pineau C. , Primig M. , Jégou B.
Published: November 2009

The efferent ducts are a series of tubules that conduct sperm from the rete testis to the epididymis. They absorb most fluid and proteins originating from the rete testis during concentration of spermatozoa prior to their entry into the epididymis. Proteome analysis of micro‐dissected efferent duct samples from adult rats was combined with genome‐wide computational prediction of conserved hormone response elements to identify factors likely regulated by oestrogens and androgens. We identified 165 proteins and found subsets of the promoters controlling their corresponding genes to contain androgen‐ and oestrogen response elements (ARE/EREs) at similar frequencies. Moreover, EREs were significantly enriched among the loci identified compared with their genome‐wide occurrence. The expression and localization of Anxa6, Ckb, Krt19, Park7, Pdzk1 and Tpt1 in the efferent ducts and other related hormone controlled tissues was further validated at the RNA or protein level. This study identifies many novel proteins predicted to play roles in sperm maturation and male fertility and provides significant computational evidence that the efferent ducts express genes transcriptionally controlled by sex hormones.
Impact of obstructive interval and sperm granuloma on patency and pregnancy after vasectomy reversal
Authors: Magheli A. , Rais‐Bahrami S. , Kempkensteffen C. , Weiske W. H. , Miller K. , Hinz S.
Published: November 2009

The objective of this study was to determine the effect of the obstructive interval and the presence of a sperm granuloma on vas patency and pregnancy rate following vasectomy reversal. We identified 334 patients with complete follow‐up who met the inclusion criteria. There were significant associations between the obstructive interval and procedure performed as well as with patient age. Patients with longer obstructive intervals were more often older (p < 0.001) and more likely to have a vaseoepididymostomy performed (p < 0.001). There was no association between the presence of a sperm granuloma or the length of the obstructive interval with post‐operative vas patency and pregnancy rates. The only independent predictor of post‐operative fertility was age of the female partner (p = 0.015). Our data clearly demonstrates that when state of the art surgical techniques are used, neither the presence of a sperm granuloma nor the obstructive interval serve as prognosticators of post‐operative vas patency and pregnancy rates. However, when counselling patients and their female partners, it is of utmost importance to stress that the age of the female partner is an independent predictor of successful vasectomy reversal.
Kisspeptin/GPR54 system as potential target for endocrine disruption of reproductive development and function
Authors: Tena‐Sempere M.
Published: November 2009

Kisspeptins, the products of Kiss1 gene acting via G protein‐coupled receptor 54 (also termed Kiss1R), have recently emerged as essential gatekeepers of puberty onset and fertility. Compelling evidence has now documented that expression and function of hypothalamic Kiss1 system is sensitive not only to the activational effects but also to the organizing actions of sex steroids during critical stages of development. Thus, studies in rodents have demonstrated that early exposures to androgens and oestrogens are crucial for proper sexual differentiation of the patterns of Kiss1 mRNA expression, whereas the actions of oestrogen along puberty are essential for the rise of hypothalamic kisspeptins during this period. This physiological substrate provides the basis for potential endocrine disruption of reproductive maturation and function by xeno‐steroids acting on the kisspeptin system. Indeed, inappropriate exposures to synthetic oestrogenic compounds during early critical periods in rodents persistently decreased hypothalamic Kiss1 mRNA levels and kisspeptin fibre density in discrete hypothalamic nuclei, along with altered gonadotropin secretion and/or gonadotropin‐releasing hormone neuronal activation. The functional relevance of this phenomenon is stressed by the fact that exogenous kisspeptin was able to rescue defective gonadotropin secretion in oestrogenized animals. Furthermore, early exposures to the environmentally‐relevant oestrogen, bisphenol‐A, altered the hypothalamic expression of Kiss1/kisspeptin in rats and mice. Likewise, maternal exposure to a complex cocktail of endocrine disruptors has been recently shown to disturb foetal hypothalamic Kiss1 mRNA expression in sheep. As a whole, these data document the sensitivity of Kiss1 system to changes in sex steroid milieu during critical periods of sexual maturation, and strongly suggest that alterations of endogenous kisspeptin tone induced by inappropriate (early) exposures to environmental compounds with sex steroid activity might be mechanistically relevant for disruption of puberty onset and gonadotropin secretion later in life. The potential interaction of xeno‐hormones with other environmental modulators (e.g., nutritional state) of the Kiss1 system warrants further investigation.
Pulsed resources affect the timing of first breeding and lifetime reproductive success of tawny owls
Authors: Millon A. , Petty S. J. , Lambin X.
Published: November 2009

1. According to life‐history theory, environmental variability and costs of reproduction account for the prevalence of delayed reproduction in many taxa. Empirical estimates of the fitness consequences of different ages at first breeding in a variable environment are few however such that the contributions of environmental and individual variability remains poorly known.

2. Our objectives were to elucidate processes that underpin variation in delayed reproduction and to assess lifetime consequences of the age of first breeding in a site‐faithful predator, the tawny owlStrix alucoL. subjected to fluctuating selection linked to cyclical variation in vole density (typically 3‐year cycles with low, increasing and decreasing vole densities in successive years).

3. A multistate capture–recapture model revealed that owl cohorts had strikingly different juvenile survival prospects, with estimates ranging from 0·08 to 0·33 respectively for birds born in Decrease and Increase phases of the vole cycle. This resulted in a highly skewed population structure with >75% of local recruits being reared during Increase years. In contrast, adult survival remained constant throughout a vole cycle. The probability of commencing reproduction was lower at age 1 than at older ages, and especially so for females. From age 2 onwards, pre‐breeders had high probabilities of entering the breeding population.

4. Variation in lifetime reproductive success was driven by the phase of the vole cycle in which female owls started their breeding career (26–47% of variance explained, whether based on the number of local recruits or fledglings), more than by age at first breeding or by conditions experienced at birth. Females who postponed reproduction to breed for the first time at age 3 during an Increase phase, produced more recruits, even when accounting for birds that may have died before reproduction. No such effects were detected for males.

5. Sex‐specific costs of early reproduction may have accounted for females being more prone to delay reproduction. Contrary to expectations from a best‐of‐a‐bad job strategy, early‐hatched, hence potentially higher‐quality females were more likely to breed at age 1, but then experienced rapidly declining food resources and so seemed caught in a life‐history trap set by the multiannual vole cycle.