HMGB1 Localization during Experimental Periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

OBSERVING BEHAVIOR AND ATYPICALLY RESTRICTED STIMULUS CONTROL

Restricted stimulus control refers to discrimination learning with atypical limitations in the range of controlling stimuli or stimulus features In the study reported here 4 normally capable individuals and 10 individuals with Intellectual disabilities (ID) performed two-sample delayed matching to sample Sample stimulus observing was recorded with an eye tracking apparatus High accuracy scores indicated stimulus control by both sample stimuli for the 4 nondisabled participants and 4 participants with ID and eye tracking data showed reliable observing of all stimuli Intermediate accuracy scores indicated restricted stimulus control for the remaining 6 participants Their eye tracking data showed that errors were related to failures to observe sample stimuli and relatively brief observing durations Five of these participants were then given interventions designed to improve observing behavior For 4 participants the interventions resulted initially in elimination of observing failures increased observing durations and Increased accuracy For 2 of these participants contingencies sufficient to maintain adequate observing were not always sufficient to maintain high accuracy subsequent procedure modifications restored It however For the 5th participant initial improvements in observing were not accompanied by improved accuracy in apparent Instance of observing without attending accuracy improved only after an additional intervention that imposed contingencies on observing behavior Thus interventions that control observing behavior seem necessary but may not always be sufficient for the remediation of restricted stimulus control

Pro-inflammatory biomarkers during experimental gingivitis in patients with type 1 diabetes mellitus: a proof-of-concept study

To compare gingival crevicular fluid (GCF) biomarker levels and microbial distribution in plaque biofilm (SP) samples for subjects with type 1 diabetes (T1DM) versus healthy subjects without diabetes during experimental gingivitis (EG).

Advanced reconstructive technologies for periodontal tissue repair

Reconstructive therapies to promote the regeneration of lost periodontal support have been investigated through both preclinical and clinical studies. Advanced regenerative technologies using new barrier-membrane techniques, cell-growth-stimulating proteins or gene-delivery applications have entered the clinical arena. Wound-healing approaches using growth factors to target the restoration of tooth-supporting bone, periodontal ligament and cementum are shown to significantly advance the field of periodontal-regenerative medicine. Topical delivery of growth factors, such as platelet-derived growth factor, fibroblast growth factor or bone morphogenetic proteins, to periodontal wounds has demonstrated promising results. Future directions in the delivery of growth factors or other signaling models involve the development of innovative scaffolding matrices, cell therapy and gene transfer, and these issues are discussed in this paper.

A global view of Staphylococcus aureus whole genome expression upon internalization in human epithelial cells

BACKGROUND: Staphylococcus aureus, a leading cause of chronic or acute infections, is traditionally considered an extracellular pathogen despite repeated reports of S. aureus internalization by a variety of non-myeloid cells in vitro. This property potentially contributes to bacterial persistence, protection from antibiotics and evasion of immune defenses. Mechanisms contributing to internalization have been partly elucidated, but bacterial processes triggered intracellularly are largely unknown. RESULTS: We have developed an in vitro model using human lung epithelial cells that shows intracellular bacterial persistence for up to 2 weeks. Using an original approach we successfully collected and amplified low amounts of bacterial RNA recovered from infected eukaryotic cells. Transcriptomic analysis using an oligoarray covering the whole S. aureus genome was performed at two post-internalization times and compared to gene expression of non-internalized bacteria. No signs of cellular death were observed after prolonged internalization of Staphylococcus aureus 6850 in epithelial cells. Following internalization, extensive alterations of bacterial gene expression were observed. Whereas major metabolic pathways including cell division, nutrient transport and regulatory processes were drastically down-regulated, numerous genes involved in iron scavenging and virulence were up-regulated. This initial adaptation was followed by a transcriptional increase in several metabolic functions. However, expression of several toxin genes known to affect host cell integrity appeared strictly limited. CONCLUSION: These molecular insights correlated with phenotypic observations and demonstrated that S. aureus modulates gene expression at early times post infection to promote survival. Staphylococcus aureus appears adapted to intracellular survival in non-phagocytic cells.

Identification of pathogen and host-response markers correlated with periodontal disease

BACKGROUND: Periodontitis is the major cause of tooth loss in adults and is linked to systemic illnesses, such as cardiovascular disease and stroke. The development of rapid point-of-care (POC) chairside diagnostics has the potential for the early detection of periodontal infection and progression to identify incipient disease and reduce health care costs. However, validation of effective diagnostics requires the identification and verification of biomarkers correlated with disease progression. This clinical study sought to determine the ability of putative host- and microbially derived biomarkers to identify periodontal disease status from whole saliva and plaque biofilm. METHODS: One hundred human subjects were equally recruited into a healthy/gingivitis group or a periodontitis population. Whole saliva was collected from all subjects and analyzed using antibody arrays to measure the levels of multiple proinflammatory cytokines and bone resorptive/turnover markers. RESULTS: Salivary biomarker data were correlated to comprehensive clinical, radiographic, and microbial plaque biofilm levels measured by quantitative polymerase chain reaction (qPCR) for the generation of models for periodontal disease identification. Significantly elevated levels of matrix metalloproteinase (MMP)-8 and -9 were found in subjects with advanced periodontitis with Random Forest importance scores of 7.1 and 5.1, respectively. The generation of receiver operating characteristic curves demonstrated that permutations of salivary biomarkers and pathogen biofilm values augmented the prediction of disease category. Multiple combinations of salivary biomarkers (especially MMP-8 and -9 and osteoprotegerin) combined with red-complex anaerobic periodontal pathogens (such as Porphyromonas gingivalis or Treponema denticola) provided highly accurate predictions of periodontal disease category. Elevated salivary MMP-8 and T. denticola biofilm levels displayed robust combinatorial characteristics in predicting periodontal disease severity (area under the curve = 0.88; odds ratio = 24.6; 95% confidence interval: 5.2 to 116.5). CONCLUSIONS: Using qPCR and sensitive immunoassays, we identified host- and bacterially derived biomarkers correlated with periodontal disease. This approach offers significant potential for the discovery of biomarker signatures useful in the development of rapid POC chairside diagnostics for oral and systemic diseases. Studies are ongoing to apply this approach to the longitudinal predictions of disease activity.

Staphylococcus aureus: new evidence for intracellular persistence

Many reports have documented that Staphylococcus aureus can invade host cells and persist intracellularly for various periods of time in cell culture models. However, it is not clear whether intracellular persistence of S. aureus also occurs in the course of infections in whole organisms. This is a subject of intense debate and is difficult to assess experimentally. Intracellular persistence would provide S. aureus with an ideal strategy to escape from professional phagocytes and extracellular antibiotics and would promote recrudescent infection. Here, we present a brief overview of the mounting evidence that S. aureus has the potential to internalize and survive within host cells.

Improving Conditions of Latino Children Brightens the Future of America

An introduction to the inaugural issue of the Journal of Applied Research on Children.

Crevicular fluid biomarkers and periodontal disease progression.

AIM Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers as predictors of periodontal disease progression (PDP). MATERIALS AND METHODS In this study, 100 individuals participated in a 12-month longitudinal investigation and were categorized into four groups according to their periodontal status. GCF, clinical parameters and saliva were collected bi-monthly. Subgingival plaque and serum were collected bi-annually. For 6 months, no periodontal treatment was provided. At 6 months, patients received periodontal therapy and continued participation from 6 to 12 months. GCF samples were analysed by ELISA for MMP-8, MMP-9, Osteoprotegerin, C-reactive Protein and IL-1β. Differences in median levels of GCF biomarkers were compared between stable and progressing participants using Wilcoxon Rank Sum test (p = 0.05). Clustering algorithm was used to evaluate the ability of oral biomarkers to classify patients as either stable or progressing. RESULTS Eighty-three individuals completed the 6-month monitoring phase. With the exception of GCF C-reactive protein, all biomarkers were significantly higher in the PDP group compared to stable patients. Clustering analysis showed highest sensitivity levels when biofilm pathogens and GCF biomarkers were combined with clinical measures, 74% (95% CI = 61, 86). CONCLUSIONS Signature of GCF fluid-derived biomarkers combined with pathogens and clinical measures provides a sensitive measure for discrimination of PDP (ClinicalTrials.gov NCT00277745).

Wound models for periodontal and bone regeneration: the role of biologic research

The ultimate goals of periodontal therapy remain the complete regeneration of those periodontal tissues lost to the destructive inflammatory-immune response, or to trauma, with tissues that possess the same structure and function, and the re-establishment of a sustainable health-promoting biofilm from one characterized by dysbiosis. This volume of Periodontology 2000 discusses the multiple facets of a transition from therapeutic empiricism during the late 1960s, toward regenerative therapies, which is founded on a clearer understanding of the biophysiology of normal structure and function. This introductory article provides an overview on the requirements of appropriate in vitro laboratory models (e.g. cell culture), of preclinical (i.e. animal) models and of human studies for periodontal wound and bone repair. Laboratory studies may provide valuable fundamental insights into basic mechanisms involved in wound repair and regeneration but also suffer from a unidimensional and simplistic approach that does not account for the complexities of the in vivo situation, in which multiple cell types and interactions all contribute to definitive outcomes. Therefore, such laboratory studies require validatory research, employing preclinical models specifically designed to demonstrate proof-of-concept efficacy, preliminary safety and adaptation to human disease scenarios. Small animal models provide the most economic and logistically feasible preliminary approaches but the outcomes do not necessarily translate to larger animal or human models. The advantages and limitations of all periodontal-regeneration models need to be carefully considered when planning investigations to ensure that the optimal design is adopted to answer the specific research question posed. Future challenges lie in the areas of stem cell research, scaffold designs, cell delivery and choice of growth factors, along with research to ensure appropriate gingival coverage in order to prevent gingival recession during the healing phase.

Distribution of abundance of planktic foraminifera and calcareous nannofossils at DSDP Sites 17-167 and 62-463

New paleomagnetic and paleontologic data from Pacific DSDP Sites 463 and 167 define the magnetic reversals that predate the Cretaceous Normal Polarity Superchron (K-N). Data from Mid-Pacific Mountain Site 463 provide the first definition of polarity chron M0 in the Pacific deep-sea sedimentary record. Foraminiferal biostratigraphy suggests that polarity chron M0 is contained entirely within the lower Aptian Hedbergella similis Zone, in agreement with foraminiferal data from the Italian Southern Alps and Atlantic Ocean. Nannofossil assemblages also suggest an early Aptian age for polarity chron M0, contrary to results from the Italian Umbrian Apennines and Southern Alps, which place polarity chron M0 on the Barremian-Aptian boundary. Biostratigraphic dating discrepancies caused by the time-transgressive, preservational, or provincial nature of paleontological species might be reconciled by the use of magnetostratigraphy, specifically polarity chron M0 which lies close to the Barremian-Aptian boundary. At Magellan Rise Site 167, five reversed polarity zones are recorded in Hauterivian to Aptian sediments. Correlation with M-anomalies is complicated by synsedimentary and postsedimentary sliding about 25 m.y. after basement formation, producing gaps in, and duplications of, the stratigraphic sequence. The magnitude and timing of such sliding must be addressed when evaluating the stratigraphy of these oceanic-rise environments.

(Table 1) Geochemistry of ODP Hole 130-807C carbonates across the K/T boundary

Paleontological, stable isotopic, trace elemental abundance, and magnetostratigraphic studies have been performed on limestones spanning the Cretaceous/Tertiary boundary transition at Ocean Drilling Program (ODP) Hole 807C. Paleontological evidence exists for considerable resedimentation, which we attribute to the fact that Hole 807C is located in a basement graben. Age estimates based on planktonic foraminiferal biostratigraphy, as well as magnetostratigraphy, indicate that sedimentation rates could have been on the order of 12-14 m/m.y. This is significantly higher than those documented in other important Deep Sea Drilling Project (DSDP) and ODP Cretaceous/Tertiary boundary sections using the same age control points (e.g., DSDP Hole 577 and ODP Hole 690B), although not as high as those documented from DSDP Hole 524. The expanded nature of this succession has resulted in the Cretaceous/Tertiary boundary d13C decrease occurring over approximately a 9-m interval. Ir analysis of these sediments do not show a single large anomaly, as has been found in other Cretaceous/Tertiary boundary sections, but trivial background levels instead. Ce data support the hypothesis that this section has been expanded by secondary sedimentological processes.

Distribution of Cretaceous redeposited benthic foraminifers at DSDP Site 89-585

Cretaceous benthic foraminifers from Site 585 in the East Mariana Basin, western Pacific Ocean, provide an environmental and tectonic history of the Basin and the surrounding seamounts. Age diagnostic species (from a fauna of 155 benthic species identified) range from late Aptian to Maestrichtian in age. Displaced species in sediments derived from the tops and flanks of nearby seamounts were deposited sporadically on the Basin floor well below the carbonate compensation depth (CCD) at abyssal depths of 5000 to 6000 m. These depths, characterized by an indigenous assemblage of benthic foraminifers, recrystallized radiolarians, fish debris, and sponge spicules, existed in the Mariana Basin from late Aptian to the present. Early Albian and older edifice-building volcanism had reached the photic zone with associated shallow-water bank or reef environments. By middle Albian, the dominant source areas subsided to outer-neritic to upper-bathyal depths. Major volcanic activity ceased and fine-grained sediments were deposited by distal turbidites, although intermittent volcanism and the influx of rare neritic material continued until the late Albian. By the Cenomanian to Turonian, upper- to middle-bathyal depths were reached by the dominant source areas, and the sediments recovered from this interval include organic carbon-rich layers. Rare benthic foraminifers from the Coniacian-Santonian interval indicate a continuation of dominantly middle-bathyal source areas. A change in sedimentation during the Campanian-Maestrichtian from older zeolitic claystone to abundant chert in the Campanian, and nannofossil chalk and claystone in the Maestrichtian resulted from migration of the site beneath the equatorial productive zone due to northwestward plate motion. The appearance of rare middle-neritic and upper-bathyal species in the Maestrichtian interval associated with volcanogenic debris gives evidence of the remobilization and downslope transport of pelagic deposits due to thermally induced uplift. Episodic redeposition of shallow-water material during the Aptian-Albian was produced by edifice-building volcanism perhaps combined with eustatic lowering of sea level. The Cenomanian-Turonian pulse coincided with a low global sea-level stand as does the transported material during the Coniacian-Santonian. The Maestrichtian pulse was caused by renewed midplate volcanism that extended over a large area of the central Pacific.