Facially Driven Digital Workflow for Maxillary and Mandibular Milled Implant- Retained Overdentures Using Two Different Unsplinted Attachment Systems: Case Report.

Unsplinted attachment systems for implant overdentures offer various benefits for edentulous patients, including cost-effectiveness, enhanced cleansability, and less need for manual dexterity. This article describes a facially driven digital workflow for fabricating a maxillary implant overdenture retained by conometric-style attachments (Atlantis® Conus) with a palateless design opposing an implant overdenture retained by standard attachments (LOCATOR®). This procedure provides a predictable and accurate technique to digitally scan the master casts with wax rims for articulation and to guide the digital teeth design set-up for a predictable esthetic outcome. The removable prosthesis workflow involves virtual teeth set-up, a 3D-printed trial denture, a milled definitive prosthesis, and intraoral pick-up for both unsplinted attachment systems. The clinical and laboratory steps are described.

Anti-inflammatory and wound healing potential of citrus auraptene.

Auraptene is the most abundant naturally occurring geranyloxycoumarin. It is primarily isolated from plants in the Rutaceae family, many of which, like citrus fruits, are used as food in many countries. Auraptene is a biologically active secondary metabolite with valuable properties. The aim of our study was to identify novel properties of auraptene with potential for managing periodontal diseases, an inflammatory disease of bacterial origin affecting the tissues surrounding and supporting the teeth. In vitro assays showed that auraptene decreased, in a dose-dependent manner, the secretion of matrix metalloproteinase 2 as well as key inflammatory mediators, including interleukin-6 (IL-6), IL-8, and chemokine (C-C motif) ligand-5 secreted by Aggregatibacter actinomycetemcomitans lipopolysaccharide-stimulated oral epithelial cells. Using gingival fibroblasts, auraptene showed a significant (P<.05) wound healing effect by its capacity to increase cell migration. In conclusion, auraptene shows promise for promoting wound healing and controlling periodontal diseases through its capacity to interfere with inflammatory mediator secretion.

Antibacterial, antiadherence, antiprotease, and anti-inflammatory activities of various tea extracts: potential benefits for periodontal diseases.

Porphyromonas gingivalis is a key etiologic agent of chronic periodontitis. This Gram-negative anaerobic bacterium produces several virulence factors and can induce a host inflammatory response that contributes to periodontal disease. In the present study, we investigated green tea, white tea, oolong tea, and black tea extracts with a high polyphenol content for their effects on (i) the growth and adherence of P. gingivalis, (ii) the activity of host and bacterial proteases, and (iii) cytokine secretion by oral epithelial cells. All the tea extracts inhibited the growth of P. gingivalis (minimal inhibitory concentrations ranging from 200 to 500 µg/mL; minimal bactericidal concentrations=500 µg/mL). In addition, they dose dependently reduced the adherence of P. gingivalis to oral epithelial cells. Tea extracts also inhibited the catalytic activity of matrix metalloproteinase (MMP)-9, neutrophil elastase, and P. gingivalis collagenase. Lastly, the tea extracts dose dependently inhibited the secretion of interleukin (IL)-6, IL-8, and chemokine (C-C motif) ligand 5 (CCL-5) by P. gingivalis-stimulated oral epithelial cells. No marked differences in the various effects were observed among the four tea extracts. Extracts from green tea, white tea, oolong tea, and black tea show promise for controlling periodontal disease by their capacity to interfere with P. gingivalis growth and virulence properties, host destructive enzymes, and inflammatory mediator secretion. Such extracts may be incorporated to oral hygiene products or locally delivered into diseased periodontal sites.

Effects of biphenyl sulfonylamino methyl bisphosphonic acids on Porphyromonas gingivalis and cytokine secretion by oral epithelial cells.

Bisphosphonate drugs are well known to inhibit osteoclastic activity and have been proposed for the management of bone diseases, including periodontitis which is associated with alveolar bone destruction. In this study, we evaluated the effects of four arylsulfonamide bisphosphonates on growth of the periodontopathogenic bacterium Porphyromonas gingivalis as well as their capacity to reduce cytokine secretion by lipopolysaccharide (LPS)-stimulated oral epithelial cells. The growth of P. gingivalis was inhibited by (4'-Chloro-biphenyl-4-sulfonylamino)methyl-1,1- bisphosphonic acid while the three other arylsulfonamide bisphosphonates ((4-Methoxy-phenylsulfonylamino)methyl-1,1- bisphosphonic acid, (4-Nitro-phenylsulfonylamino)methyl-1,1-bisphosphonic acid, and (Biphenyl-4-sulfonylamino) methyl-1,1-bisphosphonic acid) had no effect. Growth inhibition was more pronounced under an iron-restricted condition. All four arylsulfonamide bisphosphonates decreased the production of the pro-inflammatory cytokines IL-6 and IL-8 by Aggregatibacter actinomycetemcomitans LPS-stimulated oral epithelial cells. In conclusion, we uncovered additional properties of bisphosphonates that may be beneficial for the treatment of periodontal diseases. In particular, (4'-Chlorobiphenyl- 4-sulfonylamino)methyl-1,1-bisphosphonic acid combines the already disclosed antiresoptive activity with antiinflammatory and antibacterial properties.

Cranberry proanthocyanidins: natural weapons against periodontal diseases.

Cranberry ( Vaccinium macrocarpon ) is known to have a beneficial effect on several aspects of human health. Proanthocyanidins (PACs), the most abundant flavonoids extracted from red cranberry fruits, have been reported to possess antimicrobial, antiadhesion, antioxidant, and anti-inflammatory properties. Recent in vitro studies have shown that cranberry PACs may be potential therapeutic agents for the prevention and management of periodontitis, an inflammatory disease of bacterial origin affecting tooth-supporting tissues. After presenting an overview of cranberry phytochemicals and their potential for human health benefits, this review will focus on the effects of cranberry PACs on connective tissue breakdown and alveolar bone destruction, as well as their potential for controlling periodontal diseases. Possible mechanisms of action of cranberry PACs include the inhibition of (i) bacterial and host-derived proteolytic enzymes, (ii) host inflammatory response, and (iii) osteoclast differentiation and activity. Given that cranberry PACs have shown interesting properties in in vitro studies, clinical trials are warranted to better evaluate the potential of these molecules for controlling periodontal diseases.

Porphyromonas gingivalis-mediated shedding of extracellular matrix metalloproteinase inducer (EMMPRIN) by oral epithelial cells: a potential role in inflammatory periodontal disease.

Extracellular matrix metalloproteinase inducer (EMMPRIN) or CD147 is a transmembrane glycoprotein expressed by various cell types, including oral epithelial cells. Recent studies have brought evidence that EMMPRIN plays a role in periodontitis. In the present study, we investigated the effect of Porphyromonas gingivalis, a major pathogen in chronic periodontitis, on the shedding of membrane-anchored EMMPRIN and on the expression of the EMMPRIN gene by oral epithelial cells. A potential contribution of shed EMMPRIN to the inflammatory process of periodontitis was analyzed by evaluating the effect of recombinant EMMPRIN on cytokine and matrix metalloproteinase (MMP) secretion by human gingival fibroblasts. ELISA and immunofluorescence analyses revealed that P. gingivalis mediated the shedding of epithelial cell-surface EMMPRIN in a dose- and time-dependent manner. Cysteine proteinase (gingipain)-deficient P. gingivalis mutants were used to demonstrate that both Arg- and Lys-gingipain activities are involved in EMMPRIN shedding. Real-time PCR showed that P. gingivalis had no significant effect on the expression of the EMMPRIN gene in epithelial cells. Recombinant EMMPRIN induced the secretion of IL-6 and MMP-3 by gingival fibroblasts, a phenomenon that appears to involve mitogen activated protein kinases. The present study brought to light a new mechanism by which P. gingivalis can promote the inflammatory response during periodontitis.

A-type cranberry proanthocyanidins inhibit the RANKL-dependent differentiation and function of human osteoclasts.

This study investigated the effect of A-type cranberry proanthocyanidins (AC-PACs) on osteoclast formation and bone resorption activity. The differentiation of human pre-osteoclastic cells was assessed by tartrate-resistant acid phosphatase (TRAP) staining, while the secretion of interleukin-8 (IL-8) and matrix metalloproteinases (MMPs) was measured by ELISA. Bone resorption activity was investigated by using a human bone plate coupled with an immunoassay that detected the release of collagen helical peptides. AC-PACs up to 100 µg/mL were atoxic for osteoclastic cells. TRAP staining evidenced a dose-dependent inhibition of osteoclastogenesis. More specifically, AC-PACs at 50 µg/mL caused a 95% inhibition of RANKL-dependent osteoclast differentiation. This concentration of AC-PACs also significantly increased the secretion of IL-8 (6-fold) and inhibited the secretion of both MMP-2 and MMP-9. Lastly, AC-PACs (10, 25, 50 and 100 µg/ml) affected bone degradation mediated by mature osteoclasts by significantly decreasing the release of collagen helical peptides. This study suggests that AC-PACs can interfere with osteoclastic cell maturation and physiology as well as prevent bone resorption. These compounds may be considered as therapeutic agents for the prevention and treatment of periodontitis.

Proteases of Porphyromonas gingivalis as important virulence factors in periodontal disease and potential targets for plant-derived compounds: a review article.

Periodontitis is a common chronic inflammatory disorder of bacterial origin, which affects the tooth-supporting tissues. A wide range of evidences suggests that Porphyromonas gingivalis plays a key role in the initiation and progression of chronic periodontitis. This Gram-negative anaerobic bacterium produces several types of proteolytic enzymes, including gingipains, collagenases, and a dipeptidyl aminopeptidase IV. Although these enzymes have physiological functions for P. gingivalis, they have been suggested to play multiple roles in the pathogenic process of periodontitis. Indeed, P. gingivalis proteases hydrolyze a variety of serum and tissue proteins thus contributing to neutralize the immune defense system and to cause tissue destruction. Considering the key roles that P. gingivalis proteases may play in the pathogenesis of periodontitis, inhibitors of these enzymes are considered potentially new therapeutics agents. In recent years, several groups have identified natural plant-derived inhibitors effective on P. gingivalis proteases. More specifically, polyphenols isolated from cranberry and green tea were found to inhibit several proteases produced by P. gingivalis. This paper will discuss the pathological roles of P. gingivalis proteases and review the scientific literature for bioactive plant-derived compounds endowed with a capacity to inhibit these enzymes.

Modulation of matrix metalloproteinase and cytokine production by licorice isolates licoricidin and licorisoflavan A: potential therapeutic approach for periodontitis.

BACKGROUND: Inflammatory cytokines and matrix metalloproteinases (MMPs) produced by resident and inflammatory cells in response to periodontopathogens play a major role in the tissue destruction observed in periodontitis, which is a disease that affects tooth-supporting structures. In the present study, we investigate the effects of licorice-derived licoricidin (LC) and licorisoflavan A (LIA) on the secretion of various cytokines and MMPs by human monocyte-derived macrophages stimulated with Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) lipopolysaccharide (LPS). METHODS: Macrophages were treated with non-toxic concentrations of LC or LIA before being stimulated with A. actinomycetemcomitans LPS. The secretion of cytokines and MMPs and the activation of nuclear factor-kappa B (NF-κB) p65 and activator protein (AP)-1 were assessed by enzyme-linked immunosorbent assays. RESULTS: LC and LIA inhibited the secretion of interleukin (IL)-6 and chemokine (C-C motif) ligand 5 in a concentration-dependent manner but did not affect the secretion of IL-8 by LPS-stimulated macrophages. LC and LIA also inhibited the secretion of MMP-7, -8, and -9 by macrophages. The suppression of cytokine and MMP secretion by LC and LIA was associated with the reduced activation of NF-κB p65 but not that of AP-1. CONCLUSION: The present study suggests that LC and LIA have potential for the development of novel host-modulating strategies for the treatment of cytokine and/or MMP-mediated disorders such as periodontitis.

Active principles of Grindelia robusta exert antiinflammatory properties in a macrophage model.

Plant extracts and/or secondary metabolites are receiving considerable attention as therapeutic agents for treating inflammatory diseases such as periodontitis, which affects the tooth supporting tissues. The aim of this study was to investigate the effect of a Grindelia robusta extract enriched in saponins and polyphenols on Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS)-induced inflammatory mediator (IL-6, TNF-a, RANTES, MCP-1, PGE(2) ) and matrix metalloproteinase (MMP-1, -3, -7, -8, -9, -13) secretion by macrophages. LPS induced a marked increase in the secretion of all inflammatory mediators and MMPs tested by macrophages, as determined by enzyme-linked immunosorbent assays. At non-cytotoxic concentrations, the G. robusta extract inhibited dose-dependently the secretion of IL-6, RANTES, MCP-1 and, to a lesser extent, PGE(2) and TNF-a. Such inhibition was also observed for MMP-1, -3, -7, -8, -9 and -13 secretion. This ability of G. robusta extract to reduce the LPS-induced secretion of inflammatory mediators and MMPs was associated with a reduction of nuclear factor-kappa B (NF-kB) p65 activation. The results suggest that G. robusta extract possesses an antiinflammatory therapeutic potential through its capacity to reduce the accumulation of inflammatory mediators and MMPs.

Anti-Porphyromonas gingivalis and anti-inflammatory activities of A-type cranberry proanthocyanidins.

A-type cranberry proanthocyanidins (AC-PACs) have recently been reported to be beneficial for human health, especially urinary tract health. The effect of these proanthocyanidins on periodontitis, a destructive disease of tooth-supporting tissues, needs to be investigated. The purpose of this study was to investigate the effects of AC-PACs on various virulence determinants of Porphyromonas gingivalis as well as on the inflammatory response of oral epithelial cells stimulated by this periodontopathogen. We examined the effects of AC-PACs on P. gingivalis growth and biofilm formation, adherence to human oral epithelial cells and protein-coated surfaces, collagenase activity, and invasiveness. We also tested the ability of AC-PACs to modulate the P. gingivalis-induced inflammatory response by human oral epithelial cells. Our results showed that while AC-PACs neutralized all the virulence properties of P. gingivalis in a dose-dependent fashion, they did not interfere with growth. They also inhibited the secretion of interleukin-8 (IL-8) and chemokine (C-C motif) ligand 5 (CCL5) but did not affect the secretion of IL-6 by epithelial cells stimulated with P. gingivalis. This anti-inflammatory effect was associated with reduced activation of the nuclear factor-kappaB (NF-kappaB) p65 pathway. AC-PACs may be potentially valuable bioactive molecules for the development of new strategies to treat and prevent P. gingivalis-associated periodontal diseases.

Grape seed extract suppresses lipopolysaccharide-induced matrix metalloproteinase (MMP) secretion by macrophages and inhibits human MMP-1 and -9 activities.

BACKGROUND: Matrix metalloproteinases (MMPs) produced by resident and inflammatory cells in response to Gram-negative periodontopathogens play a major role in the tissue destruction observed during periodontitis, a disease that affects tooth-supporting structures. In this study, we investigated the effect of grape seed extract (GSE) on MMP secretion by human monocyte-derived macrophages stimulated with Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) lipopolysaccharide (LPS) and on the activity of human recombinant MMP-1 and -9. METHODS: Macrophages were treated with various concentrations of GSE prior to being stimulated with A. actinomycetemcomitans LPS. The secretion of MMPs and activation of nuclear factor-kappa B (NF-kappaB) p65 and activator protein-1 (AP-1) were assessed by enzyme-linked immunosorbent assay (ELISA). The effect of GSE on the catalytic activity of human recombinant MMP-1 and -9 was tested using fluorogenic assays. RESULTS: GSE inhibited the secretion of MMP-1, -3, -7, -8, -9, and -13 by LPS-stimulated macrophages in a concentration-dependent manner. The suppression of MMP secretion was associated with inhibition of NF-kappaB p65 and AP-1 activation. Also, GSE dose-dependently inhibited the activity of MMP-1 and -9. CONCLUSION: The present study suggests that GSE may be potentially used in the development of novel host-modulating strategies for the treatment of MMP-mediated disorders such as periodontitis.

Cytoprotective effect of proanthocyanidin-rich cranberry fraction against bacterial cell wall-mediated toxicity in macrophages and epithelial cells.

Recent studies brought evidence regarding the potential beneficial effects of cranberry polyphenols for periodontal infections. In this study, we evaluated the capacity of a proanthocyanidin-rich cranberry fraction to protect macrophages and oral epithelial cells against cytotoxicity induced by bacterial components. U937 cells, differentiated into adherent macrophage-like cells, as well as oral epithelial cells were treated with cell wall or lipopolysaccharide preparations from periodontopathogens. Cell viability was monitored using a commercial MTT (3-[4,5-diethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. The cytoprotective effect was evaluated by pre-incubating human cells with a proanthocyanidin-rich cranberry fraction prior to treatment with the bacterial components at toxic concentrations. Among the various bacterial components tested, Peptostreptotoccus micros cell wall was found to be the most toxic for macrophages and epithelial cells and was thus selected for further analyses. Treatment of monocyte-derived macrophages with cell wall of P. micros (20 microg/ml) decreased the cell viability by approximately 50%. Adding the cranberry fraction prior to treating cells with P. micros cell wall dose-dependently protected monocyte-derived macrophages from the toxic effect. A dose-dependent cytoprotective effect of the cranberry fraction was also observed with oral epithelial cells treated with P. micros cell wall. This study suggests that cranberry polyphenols may exert a protective effect for host cells against the toxicity induced by bacterial components.

A licorice extract reduces lipopolysaccharide-induced proinflammatory cytokine secretion by macrophages and whole blood.

BACKGROUND: Periodontal diseases are a group of inflammatory disorders initiated by specific Gram-negative periodontopathogenic bacteria that lead to the destruction of tooth-supporting tissues. In this study, we tested whether a carbon dioxide-supercritical extract of Glycyrrhiza uralensis (licorice) can reduce the periodontopathogen-induced inflammatory response. METHODS: Monocyte-derived macrophages were treated with various concentrations of the licorice extract prior to being stimulated with Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) and Porphyromonas gingivalis lipopolysaccharide (LPS). The capacity of the licorice extract to mediate the inflammatory response was also tested in an ex vivo whole blood model stimulated with P. gingivalis LPS. The secretion of interleukin (IL)-1beta, -6, and -8 and tumor necrosis factor-alpha (TNF-alpha) in both models was assessed by enzyme-linked immunosorbent assays. Changes in the phosphorylation state of macrophage intracellular kinases induced by A. actinomycetemcomitans LPS and the licorice extract in the macrophage model were characterized by immunoblotting. RESULTS: The licorice extract exhibited potent anti-inflammatory properties, inhibiting the periodontopathogen LPS-induced IL-1beta, -6, and -8 and TNF-alpha responses of macrophages. The licorice extract inhibited the phosphorylation of important macrophage intracellular signaling proteins, including nuclear factor-kappa B p65 nuclear transcription factor and Jun proto-oncogene-encoded activator protein (AP) 1 transcription factor, which are involved in inflammatory signaling pathways. The licorice extract was also a potent inhibitor of the proinflammatory cytokine response in the ex vivo human whole blood model. CONCLUSION: This CO(2)-supercritical licorice extract is a potential candidate for the development of a new therapy to prevent and/or treat periodontitis-associated tissue destruction.

Rhamnus alpinus leaf extract suppresses lipopolysaccharide-induced, monocyte-derived macrophage chemokine secretion.

Periodontitis is a chronic inflammatory disease of bacterial etiology that affects tooth-supporting tissues. The aim of the present study was to investigate the effect of Rhamnus alpinus extracts on lipopolysaccharide (LPS)-induced chemokine secretion by human macrophage-like cells. Phorbol myristic acid-differentiated macrophages were stimulated with Aggregatibacter actinomycetemcomitans LPS in the absence and presence of various concentrations of the extracts. The secretion of interleukin-8 (IL-8), regulated on activation normal T cell expressed and secreted (RANTES), and monocyte chemotactic protein (MCP)-1 was measured using enzyme-linked immunosorbent assays (ELISA). Activation of NF-kappaB p65 was evaluated with an ELISA-based kit containing immobilized oligonucleotides with an NF-kappaB consensus binding site. A. actinomycetemcomitans LPS (1 microg/ml) induced a marked increase in the secretion of IL-8 and RANTES by monocyte-derived macrophages. At non-cytotoxic concentrations, the R. alpinus leaf extract, which contains polyphenols, inhibited the secretion of RANTES and, to a lesser extent, IL-8 in a dose-dependent manner. The extract also decreased the basal levels of MCP-1 secreted by monocyte-derived macrophages. The extract appeared to exert its anti-inflammatory effect by inhibiting NF-kappaB p65 activation. Our results suggest that the leaf extract of R. alpinus possesses a therapeutic potential through its capacity to limit the infiltration of immune cells into periodontal sites. This may impede the progression and aggravation of inflammation given that the migration of immune cells plays an important role in the outcome of periodontitis.

Evidence for louse-transmitted diseases in soldiers of Napoleon's Grand Army in Vilnius.

BACKGROUND: Many soldiers in Napoleon's Grand Army died of infectious diseases during its retreat from Russia. Because soldiers were commonly infested with body lice, it has been speculated that louse-borne infectious diseases, such as epidemic typhus (caused by Rickettsia prowazekii), were common. METHODS: We investigated this possibility during recent excavations of a mass grave of Napoleon's soldiers in Vilnius, Lithuania. Segments of 5 body lice, identified morphologically and by polymerase chain reaction (PCR) amplification and sequencing, were found in earth from the grave that also contained fragments of soldiers' uniforms. RESULTS: DNA of Bartonella quintana (the agent of trench fever) was identified by PCR and sequencing in 3 of the lice. Similarly, PCR and sequencing of dental pulp from the remains of 35 soldiers revealed DNA of B. quintana in 7 soldiers and DNA of R. prowazekii in 3 other soldiers. CONCLUSIONS: Our results show that louse-borne infectious diseases affected nearly one-third of Napoleon's soldiers buried in Vilnius and indicate that these diseases might have been a major factor in the French retreat from Russia.

Bartonella quintana in domestic cat.

We recovered Bartonella quintana DNA from dental pulp of a domestic cat. This study, the first to detect B. quintana in a nonhuman mammal, changes our understanding of the epidemiology of this infection and proposes that cats may be an emerging source of human infection.

Molecular detection of Bartonella henselae DNA in the dental pulp of 800-year-old French cats.

Bartonella species are responsible for chronic bacteremia in domestic cats, which raises a question about the antiquity of the relationship between Bartonella species and cats that act as reservoirs for the organism. The sequencing of Bartonella pap31 and groEL genes from the dental pulp of cats dating from the 13th to 16th centuries identified the presence of B. henselae genotype Houston; the observation of a unique mutation in the results of PCR assays for Bartonella species ruled out modern DNA contamination of the dental pulp samples. We conclude that cats had bacteremia due to B. henselae 800 years ago.