Alexandru Bucur

Telocytes in Parotid Glands

The parotid histological structure includes acinar, ductal, and myoepithelial cells, surrounded by a connective stromal component. The parotid stroma is mostly regarded as an inert shell, consisting of septa, which divide the parenchyma. Telocytes were recently identified as a new stromal cell type in various organs, including exocrine pancreas. We aimed to evaluate telocytes presence in parotid stroma and whether their topographical features might support an involvement in parotid function modulation. Serial ultrathin sections of human and rat parotid glands were studied and compared by transmission electron microscopy. Two-dimensional concatenation of sequenced micrographs allowed the ultrastructural identification of parotid telocytes, with their specific long, thin, and moniliform prolongations (telopodes). Telocyte location appeared frequently as a strategic one, in close contact or vicinity of both secretory (acini and ducts) and regulatory (nerves and blood vessels) apparatuses. They were also found in the interacinar and the subductal stroma. Two previously reported telocyte markers (c-kit/CD117 and vimentin) were assayed by immunohistochemistry. Actin expression was also evaluated. Telocytes are making a network, especially by branching of their long telopodes. Elements of this telocyte network are interacting with each other (homocellular connections) as well as with other cell types (heterocellular connections). These interactions are achieved either by direct contact (stromal synapse), or mediated via shed microvesicles/exosomes. Since telocyte connections include both neurovascular and exocrine elements (e.g., acini and ducts), it is attractive to think that telocytes might mediate and integrate neural and/or vascular input with parotid function.

Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

BACKGROUND Head and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases. METHODS We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. RESULTS Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) < or =18.5 kg/m(2) (2.13, 1.75-2.58) and reduced for BMI >25.0-30.0 kg/m(2) (0.52, 0.44-0.60) and BMI > or =30 kg/m(2) (0.43, 0.33-0.57), compared with BMI >18.5-25.0 kg/m(2). These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI < or =18.5 kg/m(2) was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m(2) was present only in smokers and drinkers. CONCLUSIONS In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies.

A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35). Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case–control studies. Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08–1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95–1.09, P = 0.66; P-heterogeneity (Phet) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12–1.34, P = 7 × 10−6) but not males (OR = 1.02, 95% CI = 0.97–1.08, P = 0.35; Phet = 6 × 10−4). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (Phet = 0.86). Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Impact: Further research is warranted to elucidate the mechanisms underlying these observations. Cancer Epidemiol Biomarkers Prev; 20(4); 658–64. ©2011 AACR.

Inflammatory-Driven Angiogenesis in Bone Augmentation with Bovine Hydroxyapatite, B-Tricalcium Phosphate, and Bioglasses: A Comparative Study

Introduction The clinical use of bioactive materials for bone augmentation has remained a challenge because of predictability and effectiveness concerns, as well as increased costs. The purpose of this study was to analyse the ability to integrate bone substitutes by evaluating the immunohistochemical expression of the platelet endothelial cell adhesion molecules, vascular endothelial growth factor, collagen IV, laminin, and osteonectin, in the vicinity of bone grafts, enabling tissue revascularization and appearance of bone lamellae. There is a lack of in vivo studies of inflammatory-driven angiogenesis in bone engineering using various grafts. Methods The study was performed in animal experimental model on the standardized monocortical defects in the tibia of 20 New Zealand rabbits. The defects were augmented with three types of bone substituents. The used bone substituents were beta-tricalcium phosphate, bovine hydroxyapatite, and bioactive glasses. After a period of 6 months, bone fragments were harvested for histopathologic examination. Endothelial cell analysis was done by analysing vascularization with PECAM/CD31 and VEGF and fibrosis with collagen IV, laminin, and osteonectin stains. Statistical analysis was realized by descriptive analysis which was completed with the kurtosis and skewness as well as the Kruskal-Wallis and Mann-Whitney statistical tests. Results The discoveries show that the amount of bone that is formed around beta-tricalcium phosphate and bovine hydroxyapatite is clearly superior to the bioactive glasses. Both the lumen diameter and the number of vessels were slightly increased in favor of beta-tricalcium phosphate. Conclusion We can conclude that bone substitutes as bovine bone and beta-tricalcium phosphate have significant increased angiogenesis (and subsequent improved osteogenesis) compared to the bioactive glass. In our study, significant angiogenesis is linked with a greater tissue formation, indicating that in bone engineering with the allografts we used, inflammation has more benefic effects, the catabolic action being exceeded by the tissue formation.

Use of Collagen, PTFE and PRF Membranes in Bone Reconstruction an Experimental and Histomorphometric Study

Bone regeneration techniques cannot be done without barrier membranes, even if horizontal or vertical ridge augmentation and socket ridge preservation is taken into consideration. This study presents a comparison between outcomes of bone regeneration, after producing standardized bone defects followed by covering them with membranes, on an animal experimental model. The study was conducted on 18 New Zeeland rabbits, by creating 2 defects in the left tibial bone of each rabbit: one standardized defect with a diameter of 4 mm, and the second by creating 5 monocortical holes with a small round bur. The defects were augmented with bovine bone, beta-tricalcium phosphate and perioglass and they were covered with 3 types of membrane: collagen (12 defects group A), PTFE membrane (12 defects group B) and PRF membrane, made from the blood of the same rabbit (12 defects – group C). The animals were sacrificed after 6 months and analysed histomorphometrically. The new bone around graft particles has a thickness of 98.26 μm for collagen membrane, 49.19 μm for PTFE membrane and 63.98 μm for PRF membrane. The density of osteoblasts and osteocytes has an average of 0.0012 for collagen membrane, 0.0009 for PTFE membrane and 0.0010 for PRF membrane. Regarding the collagen membrane, it is observed that when used the bone regeneration appears to have a higher density of osteoforming cells and a higher quantity of