Animal Models to Study Host-Bacteria Interactions Involved in Periodontitis

Animal models have distinct advantages because they can mimic cellular complexities that occur in humans in vivo and are often more accurate than in vitro studies that take place on plastic surfaces with limited numbers of cell types present. Furthermore, cause and effect relationships can be established by applying inhibitors or activators or through the use of genetically modified animals. Such gain or loss of function studies are often difficult to achieve in human clinical studies, particularly in obtaining target tissue due to important ethical considerations. Animal models in periodontal disease are particularly important at this point in the development of the scientific basis for understanding the predominant pathological processes. Periodontal disease can be broken down into discrete steps, each of which may be studied separately depending upon the animal model. These steps involve the development of a pathogenic biofilm, invasion of connective tissue by bacteria or their products, induction of a destructive host response in connective tissue and limitation of are pair process that follows tissue breakdown. Animal studies can test hypotheses related to each of these steps, and should be evaluated by their capacity to test a specific hypothesis rather than recapitulating all aspects of periodontal disease. Thus, each of the models described below can be adapted to test discrete components of the pathological process of periodontal disease, but not necessarily all of them

Analysis of tiling array expression studies with flexible designs in Bioconductor (waveTiling)

Background: Existing statistical methods for tiling array transcriptome data either focus on transcript discovery in one biological or experimental condition or on the detection of differential expression between two conditions. Increasingly often, however, biologists are interested in time-course studies, studies with more than two conditions or even multiple-factor studies. As these studies are currently analyzed with the traditional microarray analysis techniques, they do not exploit the genome-wide nature of tiling array data to its full potential. Results: We present an R Bioconductor package, waveTiling, which implements a wavelet-based model for analyzing transcriptome data and extends it towards more complex experimental designs. With waveTiling the user is able to discover (1) group-wise expressed regions, (2) differentially expressed regions between any two groups in single-factor studies and in (3) multifactorial designs. Moreover, for time-course experiments it is also possible to detect (4) linear time effects and (5) a circadian rhythm of transcripts. By considering the expression values of the individual tiling probes as a function of genomic position, effect regions can be detected regardless of existing annotation. Three case studies with different experimental set-ups illustrate the use and the flexibility of the model-based transcriptome analysis. Conclusions: The waveTiling package provides the user with a convenient tool for the analysis of tiling array trancriptome data for a multitude of experimental set-ups. Regardless of the study design, the probe-wise analysis allows for the detection of transcriptional effects in both exonic, intronic and intergenic regions, without prior consultation of existing annotation

Prevention of water borne diseases in the tsunami affected Thotagamuwa-Hikkaduwa area of southern Sri Lanka

Thotagamuwa, Hikkaduwa in the southern coast of Sri Lanka was devastated by the Indian Ocean tsunami of December 26, 2004 leaving the affected population with poor sanitation conditions and at risk to water borne diseases and vector borne diseases. The Thotagamuwa Tsunami Relief Environmental Health Program(THOTEN) is serving a community of four thousand households towards improving the quality of drinking water through chlorination and providing for hand washing with soap-the Safe Water System(SWS).The first monitoring and evaluation survey conducted after three months of interventions are revealing that the population is beginning to use the SWS introduced under the THOTEN program. It also revealed that numbers have increased in awareness of appropriate use of soap to wash hands. The paper describes the overall approach and methodology used and the preliminary results

Impact of Impaired Glucose Metabolism on Periodontitis Progression over Three Years

We evaluated the relationship between glucose abnormalities and periodontitis in overweight/obese individuals. Eight hundred and seventy (870) diabetes-free participants aged 40–65 years completed the three-year follow-up in the San Juan Overweight Adults Longitudinal Study. The ADA thresholds for fasting and 2-h post-load glucose and HbA1c were used to define prediabetes. The NHANES methods were used to assess periodontitis. Multivariable linear regression was used to evaluate the relationship between baseline glucose metabolism measures and periodontitis at follow-up, adjusting for potential confounders. There was no association between impaired glucose measures and mean pocket depth (PD), mean clinical attachment loss (CAL), or mean percent of sites ≥5 mm PD. Impaired glucose tolerance (IGT) was associated with a lower mean percent of sites ≥5 mm CAL (β = −1.6, p = 0.037). Prediabetes and impaired fasting glucose (IFG) were associated with improvement in mean percent of sites ≥5 mm PD (β = −1.4, p = 0.022; β = −1.6, p = 0.032; respectively). IFG and IGT were associated with improvement in mean percent of sites with ≥5 mm CAL (β = −1.6, p = 0.038; β = −1.9, p = 0.020; respectively). In conclusion, there were no consistent associations between baseline prediabetes or insulin resistance and periodontitis progression over a three-year period

Viabilisation du recyclage de composites à renfort carbone et matrice thermodurcissable. Premiers éléments d'étude

À l’origine développés pour des applications hautement techniques dans l’aéronautique et le spatial, l’usage des composites à renfort carbone et matrice thermodurcissable s’élargit depuis plusieurs années aux industries de l’automobile et des sports et loisirs. Toutefois, le choix du composite dépend parfois moins de ses performances techniques, que de critères esthétiques ou de l’image de haute technicité qu’il véhicule. Il en résulte ainsi un surdimensionnement des propriétés des constituants (en particulier, de la fibre de carbone) par rapport à la fonction du produit. En outre du point de vue environnemental, il a été montré que dans la mise en œuvre du composite, c’est la production de la fibre de carbone qui est la plus impactante. Une réponse économique et environnementale à ces inadéquations consiste donc à viabiliser le développement de composites à renfort recyclé. Ainsi le recyclage du composite en fin de vie, même limité à la seule récupération des fibres, pourrait permettre de diminuer certains impacts anthropiques en réduisant les matières premières nécessaires à sa production (produits pétroliers essentiellement). En outre, ce recyclage du renfort peut être élargi aux déchets de production (fibres ou prépregs inutilisés, chutes de pièces composites, etc.). Les concepteurs seraient alors à même d’équilibrer coût et efficacité énergétique par la production de matériaux dits de seconde génération (p. ex. destinés d’abord à des pièces non-structurelles). Toutefois, viabiliser cette filière de recyclage nécessite de palier les réticences des utilisateurs en les assurant de ses bienfondés technique, économique, environnemental et législatif. Ainsi, après avoir rappelé ces différents contextes, le recyclage des composite par solvolyse de la matrice par de l’eau en conditions supercritiques, ainsi que la mise en œuvre de semi-produits de seconde génération attractifs, seront présentés. Un premier bilan économique et environnemental de cette filière sera enfin dressé

Bacterial Infection Increases Periodontal Bone Loss in Diabetic Rats Through Enhanced Apoptosis

Periodontal disease is the most common osteolytic disease in humans and is significantly increased by diabetes mellitus. We tested the hypothesis that bacterial infection induces bone loss in diabetic animals through a mechanism that involves enhanced apoptosis. Type II diabetic rats were inoculated with Aggregatibacter actinomycetemcomitans and treated with a caspase-3 inhibitor, ZDEVD-FMK, or vehicle alone. Apoptotic cells were measured with TUNEL; osteoblasts and bone area were measured in H&E sections. New bone formation was assessed by labeling with fluorescent dyes and by osteocalcin mRNA levels. Osteoclast number, eroded bone surface, and new bone formation were measured by tartrate-resistant acid phosphatase staining. Immunohistochemistry was performed with an antibody against tumor necrosis factor-α. Bacterial infection doubled the number of tumor necrosis factor-α–expressing cells and increased apoptotic cells adjacent to bone 10-fold (P \u3c 0.05). Treatment with caspase inhibitor blocked apoptosis, increased the number of osteoclasts, and eroded bone surface (P \u3c 0.05); yet, inhibition of apoptosis resulted in significantly greater net bone area because of an increase in new bone formation, osteoblast numbers, and an increase in bone coupling. Thus, bacterial infection in diabetic rats stimulates periodontitis, in part through enhanced apoptosis of osteoblastic cells that reduces osseous coupling through a caspase-3–dependent mechanism. Diabetes is a chronic inflammatory disease characterized by hyperglycemia that affects 26 million Americans.1 Diabetes has several complications, such as cardiovascular, renal, microvascular, and periodontal diseases. Periodontal disease is one of the most common forms of osteolytic bone disease and one of the most frequent complications of the diabetes.2 Recent research suggests that the relationship between periodontitis and diabetes is reciprocal.3, 4 People with diabetes are more susceptible to periodontitis, and periodontitis may affect serum glucose levels and contribute to progression of diabetes.5 Diabetes may contribute to periodontitis because of its effect on inflammation.6, 7 Despite being triggered by bacterial infection, periodontal bone loss is tied to the inflammatory host response, which leads to the generation of prostaglandins and cytokines that stimulate osteoclastogenesis and periodontal bone loss.8 Several of the detrimental aspects of periodontal disease have recently been shown to be mediated by elevated levels of tumor necrosis factor-α (TNF-α).9, 10 TNF-α is a proinflammatory cytokine produced by leukocytes and other cell types.11 Enhanced TNF-α levels have been directly linked to cellular changes in diabetic retinopathy, deficits in wound healing, and diabetes-enhanced periodontitis.12, 13, 14 Some of the detrimental effects of diabetes-enhanced TNF-α levels may be because of the induction of cell death by triggering caspase activity. Caspases are a family of cysteine proteases that can act as either initiators (caspases 2, 8, and 9) or executioners (caspases 3, 6, and 7) of apoptosis.15 Caspase-3 appears to play a central role in bacteria and lipopolysaccharide-mediated apoptosis.16, 17 In addition, it has been shown that TNF-α can stimulate the expression of several pro-apoptotic genes, many of which are regulated by the pro-apoptotic transcription factor, forkhead box-O1 (FOXO1).18 The functional role of apoptosis in pathological processes can be studied with caspase inhibitors, which are small peptides that block the activity of well-defined caspases.19 These inhibitors have been used in animal models to attenuate cell death and diminish tissue damage in ischemic conditions, sepsis, and other pathological processes.20, 21 Other studies using caspase inhibitors have shown that part of the detrimental effect of diabetes on healing after infection is the result of increased fibroblast or osteoblast apoptosis.16, 22 To understand how diabetes may affect periodontal bone loss through apoptosis, we used a caspase-3/7 inhibitor in a type 2 Goto-Kakizaki (GK) diabetic rat model of periodontal disease induced by bacterial infection. The aim of this study was to determine how apoptosis of osteoblasts contributed to periodontal bone loss by its effect on bone formation in diabetic animals

A.Actinomycetemcomitans‐Induced Periodontal Disease Promotes Systemic and Local Responses in Rat Periodontium

Aim To characterize the histologic and cellular response to A. actinomycetemcomitans (Aa) infection. Material & Methods Wistar rats infected with Aa were evaluated for antibody response, oral Aa colonization, loss of attachment, PMN recruitment, TNF‐α in the junctional epithelium and connective tissue, osteoclasts and adaptive immune response in local lymph nodes at baseline and 4, 5 or 6 weeks after infection. Some groups were given antibacterial treatment at 4 weeks. Results An antibody response against Aa occurred within 4 weeks of infection, and 78% of inoculated rats had detectable Aa in the oral cavity (p \u3c 0.05). Aa infection significantly increased loss of attachment that was reversed by antibacterial treatment (p \u3c 0.05). TNF‐α expression in the junctional epithelium followed the same pattern. Aa stimulated high osteoclast formation and TNF‐α expression in the connective tissue (p \u3c 0.05). PMN recruitment significantly increased after Aa infection (p \u3c 0.05). Aa also increased the number of CD8+ T cells (p \u3c 0.05), but not CD4+ T cells or regulatory T cells (Tregs) (p \u3e 0.05). Conclusion Aa infection stimulated a local response that increased numbers of PMNs and TNF‐α expression in the junctional epithelium and loss of attachment. Both TNF‐α expression in JE and loss of attachment was reversed by antibiotic treatment. Aa infection also increased TNF‐α in the connective tissue, osteoclast numbers and CD8+ T cells in lymph nodes. The results link Aa infection with important characteristics of periodontal destruction