Meta-regression Analysis of Study Heterogeneity for Systemic Outcomes after Periodontal Therapy.

INTRODUCTION: The contribution of periodontal disease to adverse systemic consequences remains controversial. This analysis examined 2 well-investigated conditions independently and combined-adverse pregnancy outcomes and glycemic control for patients with diabetes-based on shared pathogenic mechanisms of periodontal infection and inflammation. It was proposed that inconsistencies in study design significantly contribute to outcome discrepancies found between periodontal intervention studies undergoing meta-analysis. METHODS: Meta-analyses evaluating periodontal interventions on the rate of preterm birth and changes in glycated hemoglobin A1c in type 2 diabetes populations were conducted based on a systematic review of randomized controlled trials. Meta-regression covariates for exploring heterogeneity included sample size, level of medical management, and bias risk as moderator variables in a random-effects meta-regression. RESULTS: Systematic review identified 17 studies of diabetes and 13 of pregnancy outcomes. Analyses of these studies identified 0.50% reduction in HbA1c and 0.78 odds ratio for preterm births. The heterogeneity associated with the models was high (I2 = 92.4 and I2 = 62.7%, respectively). The adjusted models evaluating each systemic condition separately accounted for 52.2% of the effect for diabetes and 81.4% for pregnancy outcome effects independently, and 63.5% collectively, across interventional studies. CONCLUSION: This systematic review with meta-regression analysis of heterogeneity demonstrates that disparate results seen in randomized controlled trials of periodontal therapy affecting systemic outcomes may be explained in large part by study design, specifically stringency in consideration of medical management and sample size. The potential for confounding factors to influence outcomes remains a concern in understanding the implications of oral health on systemic conditions. KNOWLEDGE TRANSFER STATEMENT: The findings of this study demonstrate that much of the benefits seen from periodontal therapy on adverse systemic outcomes for diabetes and pregnancy are due to limitations in study design.

The effects of Ma-Xing-Gan-Shi-Tang on respiratory resistance and airway leukocyte infiltration in asthmatic guinea pigs.

Ma-Xing-Gan-Shi-Tang (MXGST), a traditional Chinese medicine, has been used in treatment of the bronchial asthma for several centuries. However, the therapeutic mechanisms of this Chinese medicine are still far from clear. To understand the mechanism of anti-asthmatic property of MXGST, a guinea pig model of allergic asthma was used to investigate the effects of MXGST on Dermatophagoides pteronyssinus-induced early and late asthmatic responses and airway inflammation, and examine direct beta2-adrenoceptor agonist activity in guinea-pig isolated trachea. Administration of MXGST (10 g/kg) extracts significantly inhibited the antigen induced immediate asthmatic responses (IAR) in actively sensitized guinea pig. MXGST caused concentration-dependent relaxation in strips of guinea pig trachea contracted with carbachol, and ICI-118551, a selective beta2-adrenoceptor antagonist, significantly inhibit the relaxation caused by MXGST. Furthermore, examination of bronchoalveolar lavage fluid (BALF) revealed that MXGST significantly inhibited the increase in neutrophil in the airway at 1, 6 and 24 hr after antigen challenge. Histopathologic examination results showed that MXGST suppressed the neutrophil infiltration into lung tissue. In conclusion, we suggest that the anti-asthmatic effects of MXGST are mainly due to its stimulation of beta2-adrenoceptors on bronchial smooth muscle and its anti-inflammatory ability to inhibit the neutrophil into the airway. The precise mechanism of action of MXGST in asthma remains to be elucidated.

Aspirin differentially regulates endotoxin-induced IL-12 and TNF-alpha production in human dendritic cells.

OBJECTIVE: In the development of autoimmune diseases, dendritic cells (DC) play critical roles. Here, we examined the effect of aspirin on lipopolysaccharide (LPS)-induced DC activation. METHODS: The monocyte-derived DC were established. The cytokine production was measured by ELISA, reverse transcriptase/polymerase chain reaction, or intracellular staining analyzed by flow cytometry. The expression of cell surface molecules was determined by flow cytometry. RESULTS: Aspirin inhibited LPS-induced DC maturation and costimulatory molecules expression. Aspirin, at therapeutic concentrations, also decreased LPS-induced IL-12 and IL-10 production. In contrast, the LPS-induced TNF-alpha production was enhanced by aspirin. The differential effects of aspirin on IL-12 and TNF-alpha production may not be due to down-regulation of cyclooxygenase activities. CONCLUSION: The various effects of aspirin on LPS-stimulated DC may influence the understanding of the diverse immunomodulatory mechanisms of this anti-inflammatory drug.

Oral bacteria and respiratory infection: effects on respiratory pathogen adhesion and epithelial cell proinflammatory cytokine production.

Several microbiologic and epidemiologic studies have suggested an association between dental plaque, poor oral health, and respiratory diseases such as nosocomial pneumonia and chronic obstructive pulmonary disease (COPD). A number of hypotheses are suggested to help explain how oral bacteria may participate in the pathogenesis of respiratory infection. Resident bacteria in oral secretions are likely aspirated along with respiratory pathogens and may affect the adhesion of the later organisms to the respiratory epithelium. Preliminary studies performed in our laboratory suggest that oral bacteria may modulate the adhesion of respiratory pathogens to epithelial cell lines. In addition, oral bacterial products or cytokines in oral/pharyngeal aspirates may stimulate cytokine production from respiratory epithelial cells, resulting in recruitment of inflammatory cells. The resulting inflamed epithelium may be more susceptible to respiratory infection. Further preliminary data are presented that some species of oral bacteria may induce the release of proinflammatory cytokines from epithelial cell lines to an extent similar to that seen for respiratory pathogens.

Changes in sphingolipid levels induced by epidermal growth factor in osteoblastic cells. Effects of these metabolites on cytosolic calcium levels.

Sphingolipids mediate a number of cellular functions in a variety of cell systems. The role they play in osteoblast signaling is yet unknown. This study investigated the effects of epidermal growth factor (EGF) on the levels of ceramide, sphingosine (SPH), and sphingosine-1-phosphate (S1P) in rat calvariae osteoblastic cells, and whether these metabolites mediated cytosolic calcium ([Ca2+]i) mobilization in these cells. EGF significantly (P<0.05) increased the levels of all three sphingolipids, and the phorbol ester PMA partially inhibited these effects. SPH and S1P markedly increased [Ca2+]i levels, with thapsigargin (depletes [Ca2+]i pools) decreasing the response by 60%. Verapamil (calcium channel blocker) only inhibited ceramide's effects on [Ca2+]i. Furthermore, SPH enhanced the EGF' induced increase in [Ca2+]i. This study demonstrates that ceramide, SPH and S1P mediate [Ca2+]i mobilization in rat calvarial osteoblastic cells, and that EGF induces changes in the levels of these metabolites with PKC playing an important role in the mechanisms regulating these events.

Clinical evaluation of the bone marrow imaging agent 99Tcm-phytate in the detection of bone metastases.

The aims of this study were to assess whether 99Tcm-phytate can detect metastatic skeletal lesions, and to compare it with 99Tcm-methylene diphosphonate (99Tcm-MDP) and 99Tcm-labelled human serum albumin nanocolloids (99Tcm-NC). Twenty-four patients with multiple bony metastases, investigated by 99Tcm-MDP whole-body scintigraphy, underwent 99Tcm-phytate bone marrow imaging. A separate bone marrow scintigram with 99Tcm-NC was performed in 20 of the patients. All of the metastatic lesions detected on the 99Tcm-phytate scintigrams exhibited photon-abundant foci only. Most of the 99Tcm-phytate scintigrams detected fewer metastatic lesions than the corresponding bone scintigrams. Visual comparison of the 99Tcm-NC images showed that 13 of 20 99Tcm-NC images were superior to the 99Tcm-phytate images in the detection of metastatic involvement of the skeleton. Thus 99Tcm-phytate should not be used as a bone marrow imaging agent for the detection of skeletal metastases.

Brachial and femoral blood pressures during the prenatal period.

In 202 young primigravidas, right-sided brachial and femoral arterial pressures were recorded in both supine and left lateral positions during prenatal visits in the second and third trimesters. Roll-over tests were performed in 78 of these. Position-related falls predominantly in femoral artery pressure--indicative of aortic compression-were demonstrable earlier and with greater frequency than falls predominantly in brachial artery pressure-indicative of caval compression. While the sequelae of caval compression were perceived by the gravida, those of aortic compression were not. Therefore, education to the risks of the supine position should start early in pregnancy. There was no relationship between decreases in blood pressures and subsequent development of pre-eclampsia. Roll-over tests were positive in 45 gravidas (58%) and pre-eclampsia developed in 15 (33%). Roll-over tests were negative in 33 gravidas (42%) and pre-eclampsia developed in two (6%). This difference was significant at the 0.02 level.