The effect of oral appliances that advanced the mandible forward and limited mouth opening in patients with obstructive sleep apnea: a systematic review and meta-analysis of randomised controlled trials.

Oral appliances (OAs) have demonstrated efficacy in treating obstructive sleep apnea (OSA), but many different OA devices are available. The Japanese Academy of Dental Sleep Medicine supported the use of OAs that advanced the mandible forward and limited mouth opening and suggested an evaluation of their effects in comparison with untreated or CPAP. A systematic search was undertaken in 16 April 2012. The outcome measures of interest were as follows: Apnea Hypopnea Index (AHI), lowest SpO2 , arousal index, Epworth Sleepiness Scale (ESS), the SF-36 Health Survey. We performed this meta-analysis using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Five studies remained eligible after applying the exclusion criteria. Comparing OA and control appliance, OA significantly reduced the weighted mean difference (WMD) in both AHI and the arousal index (favouring OA, AHI: -7.05 events h(-1) ; 95% CI, -12.07 to -2.03; P = 0.006, arousal index: -6.95 events h(-1) ; 95% CI, -11.75 to -2.15; P = 0.005). OAs were significantly less effective at reducing the WMD in AHI and improving lowest SpO2 and SF-36 than CPAP, (favouring OA, AHI: 6.11 events h(-1) ; 95% CI, 3.24 to 8.98; P = 0.0001, lowest SpO2 : -2.52%; 95% CI, -4.81 to -0.23; P = 0.03, SF-36: -1.80; 95% CI, -3.17 to -042; P = 0.01). Apnea Hypopnea Index and arousal index were significantly improved by OA relative to the untreated disease. Apnea Hypopnea Index, lowest SpO2 and SF-36 were significantly better with CPAP than with OA. The results of this study suggested that OAs improve OSA compared with untreated. CPAP appears to be more effective in improving OSA than OAs.

Influence of using synbiotics by various routes on Mandarah male chicks: intestinal bacterial counts, gut morphology and histological status.

This experiment investigated the influence of different synbiotic processing methods on the intestinal bacterial count, morphology and histological status of developed male Mandarah chicks. Two hundred and ten male Mandarah line chicks aged 1 d were randomized to receive one of 7 chicks. The method and dose for 1-time synbiotics administration to the day-old chicks were as follows: G1: chicks on basal diet received no treatment (control); G2: 0.25 mL synbiotics sprayed; G3: 0.50 mL synbiotics sprayed; G4: 0.25 mL of synbiotics are added to drinking water; G5: 0.50 mL of synbiotics are added to drinking water; G6: 0.25 mL of synbiotics dripped into the mouth; and G7: 0.50 mL of synbiotics dripped into mouth drops. Lactic acid bacteria(LAB) were significantly increased (P<0.0001) compared to the control group and other treated groups and had the maximum values after the use of synbiotics via drinking water (0.25 or 0.50 mL). Furthermore, when comparing the treated birds (G4, G5) with the control birds, the Escherichia coli concentration in the drinking water containing synbiotics was significantly lower. In addition, treated chickens at (G7) showed a higher duodenum, ileum villus height (VH), and VH. - Ileum crypt depth (CD) ratio compared to other groups. In addition, birds treated with 0.50 mL of synbiotics in drinking water (G5) performed better in duodenum, ileum, CD and VH. - CD ratio than the other groups. Meanwhile, intestinal tract length and visceral pH did not differ significantly between groups. It can be concluded that the use of 0.25 mL of synbiotics in drinking water can improve the overall health of birds.

Prevalence of early and late oral implant loss among smokers: a nationwide survey in Japan.

A cross-sectional, nationwide survey was conducted in Japan to examine the relationship between tobacco smoking and oral diseases including implant failure. A questionnaire survey was sent to designated facilities by post, and 158 answered questions regarding implant loss. Smoking status, number of implant failures, and other related variables were collected from the participating dentists as secondary data. A total of 1966 patients who were treated with dental implants by participating dentists during the survey period were analysed. Among the total sample, 90 (5%) had early implant loss (≤12 months) and 153 (8%) had late implant loss (>12 months and ≤120 months). The number of pack-years was significantly higher in the total (early and late) implant loss group (31.2±15.9) than in the group with no implant loss (26.1±18.1) (P=0.026). In the multivariate analysis, the number of implants installed, smoking, and pack-years were significant factors for total implant loss. The adjusted odds ratio for implant failure for current smokers compared with never smokers was 2.07 (95% CI 1.19-3.62) for early implant loss and 1.48 (95% CI 0.92-2.37) for late implant loss. This study reaffirms that current smoking is associated with an increased risk of early implant loss, irrespective of the duration of smoking exposure.

[Pulmonary venous obstruction after the Williams procedure for partial anomalous pulmonary venous connection].

A 54-year-old man was admitted to our hospital because of chest discomfort. Cardiac catheterization revealed partial anomalous pulmonary venous connection with an intact atrial septum. The right upper pulmonary vein (RUPV) drained into the upper segment of the superior vena cava (SVC). Using the Williams procedure, an atrial septal defect (ASD) was created and a fresh autologous pericardial patch was used to fashion a new pulmonary vein return route from SVC to the ASD. Although the patient was stable after the procedure, he was admitted again 6 months later because of obstruction of RUPV. At reoperation, it was found that the previous pulmonary vein route was obstructed and that the pericardial baffle had adhered to the atrial septum above the ASD. The shrunken and thickened pericardial baffle was removed and the orifice of the ASD was extensively enlarged, after which an expanded polytetrafluoroethylene (ePTFE) patch was used as a new baffle. After the reoperation, the patient's condition improved.

Contribution to oral and maxillary surgery and surgical technique of osteo-odontokeratoprosthesis in Japan.

Osteo-odontokeratoprosthesis (OOKP) is a technique invented by Strampelli in 1963, in which the patient's own tooth root is used to support an optical cylinder. It uses an autologous tooth-bone-periodontal complex to mount an optical cylinder, which is stabilised by overlying autologous buccal mucosa. OOKP involves two, staged procedures done by ophthalmologists and oral surgeons, and the main contribution from the oral surgeon is during the first stage. To date we have done nine first-stage, and completed eight second-stage, OOKP operations in Japan with a mean follow-up of eight years and 11 months by modifying the original method of the oral surgery. All OOKP procedures were unilateral, and canines were selected as the donor teeth. Patients developed ocular blindness as a result of Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and chemical and thermal burns to the cornea and ocular surface. All eight patients who completed the second stage have been stable, and there have been no major perioperative or postoperative oral complications. The patients' visual acuities were stable with no serious complications. Here we report the technical details of the oral contribution to OOKP.

Demonstration of mother-to-child transmission of Streptococcus mutans using multilocus sequence typing.

A new reliable genotyping method, multilocus sequence typing (MLST), was used to evaluate vertical transmission of the cariogenic pathogen Streptococcus mutans. A total of 136 S. mutans strains were isolated from saliva samples of 20 Japanese mother-child pairs, including 5 girls and 5 boys with primary dentition, and 5 girls and 5 boys with mixed dentition. The nucleotide sequences of 8 partial housekeeping genes, aroE, murI, gltA, glnA, glk, tkt, lepC, and gyrA, were analyzed and a similarity for all of those sequences between strains from a mother-child pair was regarded as indicating transmission, which was shown in 70% of the pairs. Interestingly, the rate of transmitted strains from mothers was significantly higher in the girls (90%) than in the boys (p = 0.001). Furthermore, the S. mutans sequence type (ST) with the highest distribution percentage in each maternal saliva sample was found to be transferred to their children. In addition, variations in two large conjugative-transfer associated regions, TnSmu1 and TnSmu2, were determined and compared with the STs defined by MLST. No variations in those two regions shown by PCR patterns were present in any of the strains isolated from the same families with the same STs, though isolates of some STs from different families showed distinct patterns for TnSmu2. Our results indicate that mothers are the main source for transmission of S. mutans to their children, while the present MLST method was also shown to be useful for investigating bacterial transmission.

Inflammatory immune responses by water-insoluble alpha-glucans.

Water-insoluble alpha-glucans are synthesized from sucrose by glucosyltransferase-I of mutans streptococci and play an important role in the development of dental plaque. Several types of beta-glucans in fungal cell wall components and water-soluble alpha-glucans from Streptococcus mutans are known to modulate innate immunity. In the present study, we investigated whether water-insoluble alpha-glucans also induced inflammatory innate immune responses. Our results showed that water-insoluble alpha-glucans synthesized by Streptococcus sobrinus activated mouse peritoneal exudate macrophages to produce pro-inflammatory cytokines. The immunological responses were not due to contamination by sucrose, water-soluble alpha-glucan, lipopolysaccharide, or peptidoglycan. Furthermore, human monocytes stimulated by water-insoluble alpha-glucans produced TNF-alpha and IL-8, while human polymorphonuclear cells were activated by water-insoluble alpha-glucans, resulting in chemotaxis and hydrogen peroxide production. The results demonstrated that water-soluble alpha-glucans modulate macrophage- and granulocyte-induced inflammatory immune responses, and suggest that inflammation induced by those alpha-glucans is associated with the development of periodontal diseases.

Oral adjuvants enhance IgA responses to Streptococcus mutans.

The induction of immune responses to orally-administered trinitrophenyl (TNP)-haptenated Streptococcus mutans or its cell wall components and enhancement of immune responses with oral adjuvants has been studied in high IgA responsive C3H/HeJ mice and in gnotobiotic rats. Gastric intubation of TNP-S. mutans to LPS non-responsive C3H/HeJ or syngeneic, LPS responsive C3H/HeN mice induced IgA responses as determined by measuring splenic plaque-forming cell (PFC) responses and IgA anti-TNP antibodies in serum, saliva, and urine. Higher IgA responses always occurred in C3H/HeJ mice given oral S. mutans antigen than similarly treated C3H/HeN animals. Oral administration of the adjuvants concanavalin A or S. mutans cell wall peptidoglycan (PG) with antigen resulted in augmented IgA responses, especially in C3H/HeJ mice. On the other hand, oral administration of muramyl dipeptide (MDP) with antigen boosted anti-TNP responses in C3H/HeN, but not in C3H/HeJ, mice. Gnotobiotic rats given S. mutans whole cells (WC) or purified cell walls (CW) by the oral route exhibited a salivary IgA immune response which was potentiated greater than twofold when antigen was given with PG or MDP. In other studies, S. mutans WC or CW antigen in water-oil-water (W/O/W) emulsion or liposomes was administered by gastric intubation to rats. Significant salivary IgA responses were induced with these antigen-adjuvant preparations. Although rats given S. mutans WC or CW were protected from S. mutans challenge, the greatest degree of caries immunity was obtained in animals which received antigen and adjuvant and which exhibited significant salivary IgA antibody levels. In preliminary studies, it was observed that local injection of rats in the salivary gland region with a ribosomal preparation from S. mutans resulted in a significant salivary IgA response and caries immunity. The potential for soluble and lipid carrier adjuvants in oral vaccines for induction of protective antibodies to S. mutans is discussed.

Molecular analysis of the inhibitory effects of oolong tea polyphenols on glucan-binding domain of recombinant glucosyltransferases from Streptococcus mutans MT8148.

An oolong tea polyphenol (OTF6) has been shown to possess a strong anti-glucosyltransferase (GTF) activity and inhibit experimental dental caries in rats infected with mutans streptococci. The effects of OTF6 on the functional domains of GTFs of Streptococcus mutans, an N-terminal catalytic domain (CAT), and a C-terminal glucan-binding domain (GBD), were examined. The maximum velocity of glucan synthesis by recombinant GTFB (rGTFB) and GTFD (rGTFD) became significantly slower in the presence of OTF6, however, Km values remained stable when compared in their absence. These results suggest that OTF6 reduces glucan synthesis by non-competitively inhibiting the GBD of S. mutans GTFB and GTFD. Further, the recombinant proteins of CAT (rCAT) and GBD (rGBD) were expressed using Escherichia coli, and purified by affinity column chromatography. rGBD but not rCAT was found to possess dextran-binding activity, which was shown to be inhibited by OTF6. These results indicate that OTF6, a polymeric polyphenol specific for oolong tea is able to reduce glucan synthesis by inhibiting the GBD of S. mutans GTFB.

Porphyromonas gingivalis fimbriae and their synthetic peptides induce proinflammatory cytokines in human peripheral blood monocyte cultures.

Porphyromonas gingivalis fimbriae as well as synthetic peptides that mimic the fimbrial subunit protein, which includes the amino acid sequence XLTXXLTXXNXX, induced high production of proinflammatory cytokines such as interleukin-1 beta, interleukin-6, interleukin-8, tumor necrosis factor-alpha in human peripheral blood monocyte/macrophage cultures. Responses induced by some peptide segments were comparable to those induced by Escherichia coli lipopolysaccharides. A chemically modified peptide analogous to an active peptide segment was found to be antagonistic with regard to interleukin-6 production induced by the native fimbriae. It may be suggested that P. gingivalis fimbriae and their degraded peptides function as proinflammatory agents in vivo, while certain analog peptides inhibited the process.

Specific interactions between Porphyromonas gingivalis fimbriae and human extracellular matrix proteins.

The interactions of the extracellular matrix (ECM) proteins (laminin, elastin, fibronectin, type I collagen, thrombospondin and vitronectin) with the fimbriae of Porphyromonas gingivalis were analyzed based on surface plasmon resonance (SPR) spectroscopy using a biomolecular interaction analyzing system (BIAcore). The BIAcore profiles demonstrated that fimbriae specifically bound to all of the ECM proteins with significant association constants (Ka). Vitronectin showed the highest affinity to fimbriae (Ka = 3.79 x 10(6) M-1), while the affinity of laminin was lowest (Ka = 2.15 x 10(6) M-1). A synthetic peptide which is a potent inhibitor of fimbrial binding to salivary proteins was not significantly effective on the fimbrial interactions with the ECM proteins. Using polystyrene microtiter plates revealed that P. gingivalis fimbriae bound markedly to immobilized fibronectin and type I collagen, while the interaction of fimbriae with the other ECM proteins was not clearly demonstrated. These results suggest that interactions between fimbriae and the ECM proteins occur with specific affinities which are not mediated by mechanisms identical to those of salivary proteins. It was also shown that SPR spectroscopy is a useful method to analyze these specific interactions.

Inconsistency between the fimbrilin gene and the antigenicity of lipopolysaccharides in selected strains of Porphyromonas gingivalis.

Immunochemical specificity of lipopolysaccharide and the molecular property of the gene encoding the fimbrilin (fimA) of Porphyromonas gingivalis strains were examined using 'fimbriated' strains 381 and HG564 and 'non-fimbriated' strains 381FL and W50. Lipopolysaccharide from strains 381, 381FL and HG564 reacted with monoclonal antibody raised to lipopolysaccharide from strain 381 to give a fused precipitin band by the immunodiffusion test. However, silver staining and Western blotting of lipopolysaccharide clearly revealed a difference in profile of bands between strains 381 and 381FL. On the other hand, lipopolysaccharide from W50 formed another precipitin band and reacted with the antibody, but only at higher concentrations of lipopolysaccharide. The fimA genes in these strains were amplified by polymerase chain reaction and cloned. Sequencing of the fimA gene revealed that the fimA(W50) was almost identical to fimA(HG564), but a notable difference was observed at the start codon of the open reading frame, while the fimA(381FL) was considerably different from fimA of other strains and its open reading frame was found to be missing. These results indicate that the molecular structure of the fimA genes of these strains is not homologous, indicating that molecular modifications in the fimA gene should occur during in vitro passages and maintenance of strains of P. gingivalis in laboratories.

Tyrosine protein phosphorylation in murine B lymphocytes by stimulation with lipopolysaccharide from Porphyromonas gingivalis.

The molecular effect of lipopolysaccharides (LPS) from porphyromonas gingivalis as well as Escherichia coli on the tyrosine protein phosphorylation in the splenic B lymphocytes from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ mice was examined. P. gingivalis LPS induced tyrosine phosphorylation of selected membrane proteins that included the phosphoproteins with apparent molecular masses of 24.8 kDa and 26.0 kDa (p24.8 and p26.) in the B lymphocytes from both strains of mice, while E. coli LPS induced p24.8 and p26.0 in C3H/HeN B Lymphocytes only. These findings suggest that through the same tyrosine phosphorylation pathway as observed in C3H/HeN B lymphocytes, P. gingivalis LPS induced the activation of C3H/HeJ B lymphocytes in which a trigger signal by E. coli LPS could not be transduced to initiate tyrosine protein phosphorylation.

Peroxidase-catalyzed generation of catechin oligomers that inhibit glucosyltransferase from Streptococcus sobrinus.

Oolong tea extract (OTE) and the purified polymeric polyphenols from OTE have been found to inhibit glucosyltransferase (GTase) of mutans streptococci. In view of the partial fermentation characteristic of oolong tea, we describe here an in vitro model reaction system to produce partially fermented products of D-(+)-catechin or green tea extract (GTE) using horseradish peroxidase. A dimeric catechin molecule was identified as dehydro-dicatechin A by instrumental analyses. The molecular size of some oligomeric catechins was estimated by the elution profile with HPLC. These catechin oligomers markedly inhibited GTase from Streptococcus sobrinus 6715. As the degree of polymerization of catechin or GTE increased, GTase was inhibited more effectively. These results suggest that polymeric polyphenols found in OTE are synthesized by partial fermentation due to oxidases/peroxidases present in tea leaves.

Humoral and cellular immune responses to the fimbriae of Porphyromonas gingivalis and their synthetic peptides.

Subcutaneous injection of fimbriae from Porphyromonas gingivalis strain 381 in Freund's incomplete adjuvant (FIA) resulted in an excellent serum anti-fimbrial immunoglobulin G (IgG) response in guinea-pigs and BALB/c mice. Administration of P. gingivalis fimbriae also elicited distinct cellular immune responses to the fimbriae in terms of ear lobe reaction in BALB/c but not in BALB/c nu/nu mice, and of skin reaction in guinea-pigs. When the guinea-pigs were given a semi-synthetic adjuvant GM-53--sodium beta-N-acetylglycosaminyl-(1-->4)-N-acetylmuramyl-L-alanyl-D-isogl utaminyl- (L)-stearoyl-(D)-meso-2, 6-diaminopimelic acid-(D)-amide-D-alanine--and fimbriae in FIA by subcutaneous injection, more enhanced production of serum anti-fimbrial IgG and stronger cellular immune responses were induced in the guinea-pigs than in those given fimbriae alone. Synthetic peptide FP381(202-221), which corresponds to the amino-acid residue numbers 202-221 based on the amino-acid sequence of fimbrilin from P. gingivalis strain 381, elicited humoral and cellular immune responses in guinea-pigs immunised with the fimbriae or FP381(202-221). Furthermore, subcutaneous administration of synthetic peptide FP381(61-80) with GM-53 induced lesser degrees of humoral and cellular immune responses in guinea-pigs than did FP381(202-221). However, when the fimbriae or FP381(61-80) were administered with bovine serum albumin (BSA), markedly elevated levels of specific anti-BSA antibody were seen in the serum of BALB/c mice. These results clearly indicated that fimbriae from P. gingivalis 381 and their oligopeptide segments induced humoral and cellular immune responses and exhibited immuno-adjuvant activities in guinea-pigs and BALB/c mice.

Virulence factors of Streptococcus mutans and dental caries prevention.

Streptococcus mutans possesses the abilities to adhere to pellicle-coated tooth surfaces and to form acids - two characteristics associated with the cariogenicity of this micro-organism. De novo synthesis of insoluble glucan by S. mutans glucosyltransferase from sucrose is essential in the adherence process. Therefore, agents which interfere with the adherence ability of S. mutans would be useful for controlling dental caries. In the present report, we have summarized our recent findings concerning virulence factors of S. mutans and means for prevention of S. mutans-induced dental caries.

Adherence of serotype e Streptococcus mutans and the inhibitory effect of Lancefield group E and S mutans type e antiserum.

S mutans strain MT703 from an active carious lesion in the tooth of a child had type e specificity and showed a cross-reaction with the Lancefield group E cell wall streptococcal polysaccharide antigen. Heat-killed cells MT703 adhered to a glass surface in the presence of CGT MT703 and sucrose. Pretreatment of the cells with anti-MT703 whole cell serums inhibited adherecne. The removal of glycerol teichoic acid antibody and group E antibody from the MT703 serum did not result in a loss of inhibitory activity. Antiserum with or without adsorption significantly inhibited glucan synthesis by CGT from sucrose. Antibodies specific for the polyglycerol phosphate of teichoic acid did not inhibit adherence. Anti-group E serum and serums specific for other types of S mutans, did not show adherence inhibitory activity except for an occasional type c specific antiserum. Antibody specific for the type e antigen produced significant inhibition of the binding of CGT to the MT703 cell wall, and adherence of these cells did not occur. Antibody to CGT inhibited glucan synthesis. Treatment of the cells with dextranase, dextran antibody, or trypsin caused a significant reduction in adherence. The results suggest that the type antigen and dextran on the surface of the S mutans type e cell are functional in adherence, and that these polymers are associated with cell wall protein.

Susceptibility of rats, hamsters, and mice to carious infection by Streptococcus mutans serotype c and d organisms.

Susceptibility of rats, hamsters, and mice to carious infection by S. mutans serotypes c and d was compared. S. mutans serotype c induced a similar level of carious lesions at experimental periods of 68, 82, and 98 d in rats, hamsters, and mice, respectively. On the other hand, S. mutans serotype d developed a high level of caries at those experimental periods in rats and hamsters, whereas in mice it showed weak caries activity.

Synergistic effects of streptococcal glucosyltransferases on adhesive biofilm formation.

Glucosyltransferases (GTF)-I and GTF-SI of Streptococcus mutans synthesize water-insoluble and both water-soluble and -insoluble glucans, respectively, and play essential roles in the sucrose-dependent adhesion of the organism to tooth surfaces. To examine the interactions of different GTFs on artificial biofilm formed by S. mutans and other oral streptococci, we generated GTF-I- and GTF-SI-hyperproducing isogenic mutant strains. Transformant B42-21, which hyperexpressed GTF-SI, exhibited firm adhesion in the presence of sucrose, whereas transformant B42-10, which hyperexpressed GTF-I, failed to exhibit firm adhesion. Furthermore, co-culture of transformant B42-21 with water-soluble glucan-synthesizing Streptococcus sanguinis yielded firm adhesion, while the addition of dextran T10 to B42-21 growing culture had no effect on adhesion. These findings suggest that GTF-SI has a strong effect on sucrose-dependent adhesion and is essential for biofilm formation on smooth surfaces, in cooperation with water-soluble glucans synthesized de novo by oral streptococci that inherently lack cell adhesion ability.

Differential and quantitative analyses of mRNA expression of glucosyltransferases from Streptococcus mutans MT8148.

Streptococcus mutans produces three glucosyltransferases, coded by gtfB, gtfC, and gtfD, whose cooperative action is essential for sucrose-dependent cellular adhesion. This cellular adhesion plays an important role in the formation of dental plaque and the initiation of dental caries. Since they bear genetic similarities and are large in size, differentiation of their gene expression has been difficult, and little is known about the dynamic process of gtf expression. Using a real-time reverse-transcription/polymerase chain-reaction, we determined the expression of each gtf. Under various conditions, the relative levels of transcription were gtfB > gtfD > gtfC. Sucrose enhanced gtfD expression, whereas it reduced that of gtfB and gtfC, suggesting the presence of independent promoters. Quantitative analyses demonstrated coincidence between the ratio of expression of each gtf and the ratio previously identified as optimal for sucrose-dependent adhesion in vitro, suggesting that S. mutans produces GTF at an optimal ratio to adhere to the tooth surface.