Synthesis of DPIE [2-(1,2-Diphenyl-1H-indol-3-yl)ethanamine] Derivatives and Their Regulatory Effects on Pro-Inflammatory Cytokine Production in IL-1ß-Stimulated Primary Human Oral Cells.

Interleukin-1 beta (IL-1ß) has diverse physiological functions and plays important roles in health and disease. In this report, we focus on its function in the production of pro-inflammatory cytokines, including IL-6 and IL-8, which are implicated in several autoimmune diseases and host defense against infection. IL-1ß activity is markedly dependent on the binding affinity toward IL-1 receptors (IL-1Rs). Several studies have been conducted to identify suitable small molecules that can modulate the interactions between 1L-1ß and 1L-1R1. Based on our previous report, where DPIE [2-(1,2-Diphenyl-1H-indol-3-yl)ethanamine] exhibited such modulatory activity, three types of DPIE derivatives were synthesized by introducing various substituents at the 1, 2, and 3 positions of the indole group in DPIE. To predict a possible binding pose in complex with IL-1R1, a docking simulation was performed. The effect of the chemicals was determined in human gingival fibroblasts (GFs) following IL-1ß induction. The DPIE derivatives affected different aspects of cytokine production. Further, a group of the derivatives enabled synergistic pro-inflammatory cytokine production, while another group caused diminished cytokine production compared to DPIE stimulation. Some groups displayed no significant difference after stimulation. These findings indicate that the modification of the indole site could modulate IL-1ß:IL1R1 binding affinity to reduce or enhance pro-inflammatory cytokine production.

Resveratrol enhances bone formation by modulating inflammation in the mouse periodontitis model.

OBJECTIVE: To evaluate the effect of resveratrol on periodontal bone regeneration after local delivery and to determine its effect on inflammatory mediators. BACKGROUND: Resveratrol is considered an anti-inflammatory polyphenolic stilbene involved in the modulation of inflammation. MATERIALS AND METHODS: Periodontitis was induced in mouse molars using a 5-day ligature model followed by the left second molar extraction and 50 µM resveratrol treatment for 1 and 2 weeks. We then examined specimens treated for 1 week histologically and with immunostaining. Microfocus-computed tomography (micro-CT) was used to examine the bone volume formation. RESULTS: After 1 week of treatment, proinflammatory cytokine levels (TNF-alpha and IL6), cells exhibiting neutrophil and macrophage marker (MPO), cell proliferation marker (Ki67), and preosteoblastic marker (RUNX2) reactivity decreased in the resveratrol-treated specimens compared to the control group. In contrast, we observed a higher number of CD31-, F4/80-, and osteocalcin- (OCN-) positive cells in the resveratrol-treated specimens. After 2 weeks, micro-CT confirmed an increased bone mass in the region of the extraction socket in the resveratrol-treated group. CONCLUSION: After 1 week, the resveratrol-treated specimens revealed evidence of inflammation modulation compared to the control group. These data suggest that resveratrol not only affects inflammation control but also is useful for treating periodontitis-related tissue defects and bone regeneration.

Efficacy of a modified short fully covered self-expandable metal stent for perihilar benign biliary strictures.

BACKGROUND AND AIM: Endoscopic management of a benign biliary stricture (BBS) on the hilum is complicated and challenging. Although the placement of a fully covered self-expandable metal stent (FCSEMS) is possible to increase effectiveness, stent migration and stent-induced adverse events are problematic. We aimed to evaluate the usefulness of a modified short FCSEMS with a long lasso in patients with a difficult perihilar BBS. METHODS: Patients with perihilar BBS within 2 cm from the hilar confluence that failed initially with plastic stents were enrolled. A modified short FCSEMS was deployed and then removed 5-6 months later. The primary outcome was clinical success. Other technical success, adverse events, endoscopic success of stent removal, and recurrence of stricture during the follow-up period were measured. RESULTS: Endoscopic intraductal placement was technically successful in all patients (n = 19). Combined contralateral plastic stent placement was performed in 13 patients (68.4%). The median duration of stent placement was 163 days (range, 138-196 days). Endoscopic stent removal was successful in all patients except one spontaneous distal migration. Stricture resolution without de novo focal stricture occurrence was 100%. Endoscopic stone removal after stricture improvement was successful in all 13 patients with bile duct stones above the stricture. During a follow-up period (median 635 days) after stent removal, only one recurrence developed. CONCLUSIONS: Temporary placement of a modified intraductal short FCSEMS with or without a contralateral plastic stent improved perihilar BBS in patients that primarily failed by plastic stents. Combined biliary stones were also successfully removed after stricture resolution.

Biliary stenting for hilar malignant biliary obstruction.

Although endoscopic intervention is the mainstay for palliation of malignant biliary obstruction, a percutaneous approach has been preferred, particularly in patients with advanced high-grade hilar malignant biliary obstruction, because of the technical difficulty and risk of complications. However, recently, primary endoscopic palliation using plastic or metal stents has had higher technical and clinical success with fewer adverse events than the percutaneous approach. Endoscopic interventions are being done more and more frequently because of advances in metal stents, accessories, and techniques. However, several concerns, such as optimal stent type, number, and deployment method, remain to be resolved. Therefore, we reviewed the literature in order to identify the optimal biliary stenting strategy for patients with hilar malignant biliary obstruction, focusing on stent type (plastic vs metal), number (unilateral [single] vs bilateral [multiple]), and deployment method (stent-in-stent vs stent-by-stent).

Osmunda japonica Extract Suppresses Pro-Inflammatory Cytokines by Downregulating NF-κB Activation in Periodontal Ligament Fibroblasts Infected with Oral Pathogenic Bacteria.

Periodontal diseases are caused by bacterial infection and may progress to chronic dental disease; severe inflammation may result in bone loss. Therefore, it is necessary to prevent bacterial infection or control inflammation. Periodontal ligament fibroblasts (PDLFs) are responsible for the maintenance of tissue integrity and immune and inflammatory events in periodontal diseases. The formation of bacterial complexes by Fusobacterium nucleatum and Porphyromonas gingivalis is crucial in the pathogenesis of periodontal disease. F. nucleatum is a facultative anaerobic species, considered to be a key mediator of dental plaque maturation and aggregation of other oral bacteria. P. gingivalis is an obligate anaerobic species that induces gingival inflammation by secreting virulence factors. In this study, we investigated whether Osmunda japonica extract exerted anti-inflammatory effects in primary PDLFs stimulated by oral pathogens. PDLFs were stimulated with F. nucleatum or P. gingivalis. We showed that pro-inflammatory cytokine (IL-6 and IL-8) expression was induced by LPS or bacterial infection but decreased by treatment with O. japonica extract following bacterial infection. We found that the activation of NF-κB, a transcription factor for pro-inflammatory cytokines, was modulated by O. japonica extract. Thus, O. japonica extract has immunomodulatory activity that can be harnessed to control inflammation.

Safety and efficacy of a metal stent covered with a silicone membrane containing integrated silver particles in preventing biofilm and sludge formation in endoscopic drainage of malignant biliary obstruction: a phase 2 pilot study.

BACKGROUND AND AIMS: Membrane-covered self-expandable metal stents (SEMSs) have been developed to prolong the patency of stents by reducing tissue hyperplasia or tumor ingrowth. However, their effectiveness is attenuated by stent clogging as a result of biofilm formation on the inner surface of the membrane. The aim of this pilot study was to evaluate the efficacy and safety of SEMSs covered with a silicone membrane containing integrated silver particles (Ag-P) in malignant distal biliary obstruction. METHODS: Twenty-four patients who underwent SEMS placement because of malignant distal biliary obstruction were enrolled in this single-center pilot study. The main outcomes were technical success, clinical success, adverse events, stent patency, and survival. RESULTS: The technical and clinical success rates were 100% and 91.7% (22 of 24), respectively. The rates of early and late adverse events were 22.7% and 36.4%, respectively. The primary reintervention rate was 27.3% (6 of 22). Only 1 case involving stent malfunction was associated with sludge impaction. Median stent patency was 179 days. During follow-up, there were no serious adverse events or mortality related to the stents or Ag-P. Serum and urine silver concentrations before and after stent placement and at 32 weeks after placement did not differ. All serum and urine silver concentrations were <3 µg/L (3 ppb) and 5 µg/L (5 ppb), respectively. CONCLUSIONS: SEMSs covered with a silicone membrane containing integrated Ag-Ps may be effective and safe in malignant distal biliary obstruction. Stent dysfunction related to sludge impaction may be less frequent using this new stent. (Clinical Research Information Service identifier: KCT 0002310.).

Effects of oleanolic acid acetate on bone formation in an experimental periodontitis model in mice.

OBJECTIVE: We evaluated the role of oleanolic acid acetate (OAA), a triterpenoid commonly used in the treatment of liver disorders, inflammatory diseases, and metastasis, in bone formation after tooth loss by periodontitis. BACKGROUND: Periodontitis causes the sequential degradation of the alveolar bone and associated structures, resulting in tooth loss. Several studies have attempted to regenerate the bone for implantation following tooth loss. METHODS: Maxillary left second molar was extracted from 8-week-old male mice following induction of periodontitis by ligature for 5 days. The extraction socket was treated with 50 ng/µL OAA for 1, 2, and 3 weeks. Detailed morphological changes were examined using Masson's trichrome staining, and the precise localization patterns of various signaling molecules, including CD31, F4/80, interleukin (IL)-6, and osteocalcin, were observed. The volume of bone formation was examined by Micro-CT. Osteoclasts were enumerated using tartrate-resistant acid phosphatase (TRAP) staining. For molecular dissection of signaling molecules, we employed the hanging-drop in vitro cultivation method at E14 for 1 day and examined the expression pattern of transforming growth factor (TGF)-ß superfamily and Wnt signaling genes. RESULTS: Histomorphometrical examinations showed facilitated bone formation in the extraction socket following OAA treatment. In addition, OAA-treated specimens showed the altered localization patterns of inflammatory and bone formation-related signaling molecules including CD31, F4/80, IL-6, and osteocalcin. Also, embryonic tooth germ mesenchymal tissue cultivation with OAA treatment showed the significant altered expression patterns of signaling molecules such as transforming growth factor (TGF)-ß superfamily and Wnt signaling. CONCLUSIONS: Oleanolic acid acetate induces bone formation and remodeling through proper modulation of osteoblast, osteoclast, and inflammation with regulations of TGF-ß and Wnt signaling.

Modified non-flared fully covered self-expandable metal stent versus plastic stent for preoperative biliary drainage in patients with resectable malignant biliary obstruction.

BACKGROUND AND AIM: Fully covered self-expandable metal stents (FCSEMS) may be better than plastic stents (PS) for preoperative biliary drainage (PBD) to relieve cholangitis or jaundice for resectable malignant biliary obstruction (MBO). However, modification of current FCSEMS designed originally for nonresectable MBO is needed to be a proper stent for PBD. The aim of this study was to evaluate the possible superiority of non-flared modified FCSEMS (M-FCSEMS) with 12-mm diameter and waist of central portion over PS in patients with resectable MBO. METHODS: Eighty-five consecutive patients underwent PBD followed by operation from August 2015 to December 2017. In each M-FCSEMS and PS group, 29 patients were matched for age, sex, body mass index, and preoperative albumin and bilirubin levels. RESULTS: The overall technical success rates of PBD using M-FCSEMS and PS were 100%. The time to operation was similar between groups (18.6 ± 10.8 vs 19.3 ± 11.6 days, respectively; P = 0.843). The prevalence of PBD-related adverse events (AEs) was 6.9% (2/29) in the M-FCSEMS group versus 27.6% (8/29) in the PS group (P = 0.037). Re-intervention before operation was required in 20.7% (6/29) of patients in the PS group but no patients in the M-FCSEMS group (P = 0.023). No differences were found between perioperative AEs in the M-FCSEMS and PS groups (27.5% vs 31.0%, respectively; P = 0.773). CONCLUSION: Modified FCSEMS led to lower PBD-related AEs, re-intervention rate, and comparable perioperative AEs compared with PS. M-FCSEMS may be a potential novel stent for PBD in patients with resectable MBO.

Litsea japonica Leaf Extract Suppresses Proinflammatory Cytokine Production in Periodontal Ligament Fibroblasts Stimulated with Oral Pathogenic Bacteria or Interleukin-1ß.

Periodontal disease, a chronic disease caused by bacterial infection, eventually progresses to severe inflammation and bone loss. Regulating excessive inflammation of inflamed periodontal tissues is critical in treating periodontal diseases. The periodontal ligament (PDL) is primarily a connective tissue attachment between the root and alveolar bone. PDL fibroblasts (PDLFs) produce pro-inflammatory cytokines in response to bacterial infection, which could further adversely affect the tissue and cause bone loss. In this study, we determined the ability of Litsea japonica leaf extract (LJLE) to inhibit pro-inflammatory cytokine production in PDLFs in response to various stimulants. First, we found that LJLE treatment reduced lipopolysaccharide (LPS)-induced pro-inflammatory cytokine (interleukin-6 and interleukin-8) mRNA and protein expression in PDLFs without cytotoxicity. Next, we observed the anti-inflammatory effect of LJLE in PDLFs after infection with various oral bacteria, including Fusobacterium nucleatum, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. These anti-inflammatory effects of LJLE were dose-dependent, and the extract was effective following both pretreatment and posttreatment. Moreover, we found that LJLE suppressed the effect of interleukin-1 beta-induced pro-inflammatory cytokine production in PDLFs. Taken together, these results indicate that LJLE has anti-inflammatory activity that could be exploited to prevent and treat human periodontitis by controlling inflammation.

DPIE [2-(1,2-diphenyl-1H-indol-3-yl)ethanamine] Augments Pro-Inflammatory Cytokine Production in IL-1ß-Stimulated Primary Human Oral Cells.

Interleukin-1β (IL-1β) is a prominent pro-inflammatory cytokine that is implicated in a variety of autoimmune diseases and plays an important role in host defense against infections. IL-1β activity increases with its increasing binding capacity to IL-1 receptors (IL-1Rs). Thus, numerous studies have targeted the discovery of molecules modulating the interactions between IL-1β and IL-1R1. We have conducted an IL-1R1 structure-based virtual screening to identify small molecules that could alter IL-1β activity, using in silico computational analysis. Sixty compounds from commercial libraries were predicted to bind to IL-1R1, and their influence on cytokine production in IL-1β-stimulated gingival fibroblasts (GFs) was determined. Of these, only (2-(1,2-diphenyl-1H-indol-3-yl)ethanamine (DPIE) showed a synergistic increase in inflammatory molecules and cytokine production (IL-6, IL-8, and COX-2) at both mRNA and protein levels in IL-1β-stimulated GFs. The enhancing activity of DPIE in IL-1β-induced cytokine production increased in a dose-dependent manner without cytotoxicity. This pattern was also observed in IL-1β-stimulated primary human periodontal ligament cells (PDLs). Furthermore, we measured the impact of DPIE on the IL-1β⁻IL-1R1 system using surface plasmon resonance and demonstrated that DPIE increased the binding affinity of IL-1β to IL-1R1. These data indicate that DPIE boosts IL-1β signaling by enhancing the binding of IL-1β to IL-1R1 in oral primary cells.

NOX1/2 activation in human gingival fibroblasts by Fusobacterium nucleatum facilitates attachment of Porphyromonas gingivalis.

Periodontal diseases are infectious polymicrobial inflammatory diseases that lead to destruction of the periodontal ligament, gingiva, and alveolar bone. Sequential colonization of a broad range of bacteria, including Fusobacterium nucleatum and Porphyromonas gingivalis, is an important phenomenon in this disease model. F. nucleatum is a facultative anaerobic species thought to be a key mediator of dental plaque maturation due to its extensive coaggregation with other oral bacteria, while P. gingivalis is an obligate anaerobic species that induces gingival inflammation by secreting various virulence factors. The formation of a bacterial complex by these two species is central to the pathogenesis of periodontal disease. Reactive oxygen species (ROS) are produced during bacterial infections and are involved in intracellular signaling. However, the impact of oral bacteria-induced ROS on the ecology of F. nucleatum and P. gingivalis has yet to be clarified. In the present study, we investigated ROS production induced in primary human oral cells by F. nucleatum and P. gingivalis and its effect on the formation of their bacterial complexes and further host cell apoptosis. We found that in primary human gingival fibroblasts (GFs), two NADPH oxidase isoforms, NOX1 and NOX2, were activated in response to F. nucleatum infection but not P. gingivalis infection. Accordingly, increased NADPH oxidase activity and production of superoxide anion were observed in GFs after F. nucleatum infection, but not after P. gingivalis infection. Interestingly, in NOX1, NOX2, or NOX1/NOX2 knockdown cells, the number of P. gingivalis decreased when the cells were coinfected with F. nucleatum. A similar pattern of host cell apoptosis was observed. This implies that F. nucleatum contributes to attachment of P. gingivalis by triggering activation of NADPH oxidase in host cells, which may provide an environment more favorable to strict anaerobic bacteria and have a subsequent effect on apoptosis of host cells.

Disparities in the experience and treatment of dental caries among children aged 9-18 years: the cross-sectional study of Korean National Health and Nutrition Examination Survey (2012-2013).

BACKGROUND: The aim of this study is to examine the association between parental socioeconomic status (SES) and the experience as well as treatment of dental caries among children aged 9 to 18 years. METHODS: Data from 1253 children aged 9-18 years from the Korean National Health and Nutrition Examination Survey (2012-2013) were analyzed. Parental socioeconomic status was measured using household income level and maternal educational level. The decayed, missing, and filled teeth (DMFT) index was used to measure experience of dental caries (DMFT ≥ 1). Non-treatment of dental caries was measured according to whether the participants who experienced dental caries used a dental service at a dental clinic to treat caries during the previous year. Logistic regression was used to investigate the association between parental socioeconomic status and the experience of dental caries as well as the association between parental socioeconomic status and the non-treatment of dental caries among children that have experienced caries. RESULTS: A total of 808 subjects (64.5 %) experienced dental caries among 1253 participants, and 582 of these 808 subjects (72.0 %) did not receive treatment among those having experience of dental caries. Parental socioeconomic status was not associated with experience of dental caries. However, those from low- and middle-income households were less likely to receive treatment than those from high-income households (odds ratio [OR] 2.11 [95 % confidence interval (CI) 1.16-3.86], OR 2.14 [95 % CI 1.27-3.62]). In particular, those from low- and middle-income households who had regular dental checkups were more likely to have untreated caries than those from high-income households (OR 3.58 [95 % CI 1.25-10.24]). CONCLUSIONS: This study demonstrates the parental household income-related disparities in children's dental health treatment. Efforts should be made to lower financial barriers to dental health services, particularly among those from low-income households, in order to reduce dental health disparities in the treatment of caries in children.

Polymeric embolization coil of bilayered polyvinyl alcohol strand for therapeutic vascular occlusion: a feasibility study in canine experimental vascular models.

PURPOSE: To investigate the feasibility of polyvinyl alcohol (PVA) polymer coil as a new endovascular embolic agent and to gauge the related histologic response in a canine vascular model. MATERIALS AND METHODS: PVA polymer coil was fabricated by cross-linking PVA and tantalum particles. Basic properties were then studied in vitro via swelling ratio and bending diameter. Normal renal segmental arteries and wide-necked aneurysms of carotid sidewalls served as canine vascular models. Endovascular PVA coil embolization of normal renal segmental arteries (N = 20) and carotid aneurysms (N = 8) was performed under fluoroscopic guidance in 10 dogs. Degree of occlusion was assessed immediately and at 4 weeks after embolization by conventional and computed tomographic angiography. Histologic features were also graded at acute (day 1, six segmental arteries and four aneurysms) and chronic phases (week 4, 14 segmental arteries and four aneurysms) after embolization to assess inflammation, organization of thrombus, and neointimal proliferation. RESULTS: Swelling ratio declined as concentrations of cross-linking agent increased. Mean bending diameters were 2.05 mm (range, 0.86-6.25 mm) in water at 37 °C and 2.29 mm (range, 0.94-6.38 mm) in canine blood samples at 37 °C. Occlusion of normal renal segmental arteries was sustained (complete occlusion at day 1, n = 20; at week 4, n = 14), whereas immediate outcomes in carotid aneurysms (day 1, complete occlusion, n = 5; residual neck only, n = 3) were not sustained (week 4, complete occlusion, n = 1; minor recanalization, n = 1; major recanalization, n = 2). At week 4, chronic inflammatory cells predominated, with progressive organization of thrombus and fibrocellular ingrowth. All aneurysms bore full neointimal linings on the coil mass in the chronic phase. CONCLUSIONS: Vascular occlusion by PVA polymer coil proved superior in normal renal segmental arteries and feasible in surgically constructed carotid aneurysms (with packing densities ≥ 30%), constituting acceptable radiologic feasibility and histologic response.

Proteomic analysis of gingival tissue and alveolar bone during alveolar bone healing.

Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build-up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven useful for studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare proteins with altered expression in gingival soft tissue and alveolar bone following tooth extraction. For target identification and validation, hard and soft tissue were extracted from mini-pigs at the indicated times after tooth extraction. From triplicate experiments, 56 proteins in soft tissue and 27 proteins in alveolar bone were found to be differentially expressed before and after tooth extraction. The expression of 21 of those proteins was altered in both soft tissue and bone. Comparison of the activated networks in soft tissue and alveolar bone highlighted their distinct responsibilities in bone and tissue healing. Moreover, we found that there is crosstalk between identified proteins in soft tissue and alveolar bone with respect to cellular assembly, organization, and communication. Among these proteins, we examined in detail the expression patterns and associated networks of ATP5B and fibronectin 1. ATP5B is involved in nucleic acid metabolism, small molecule biochemistry, and neurological disease, and fibronectin 1 is involved in cellular assembly, organization, and maintenance. Collectively, our findings indicate that bone regeneration is accompanied by a profound interaction among networks regulating cellular resources, and they provide novel insight into the molecular mechanisms involved in the healing of periodontal tissue after tooth extraction.

Technical feasibility and revision efficacy of the sequential deployment of endoscopic bilateral side-by-side metal stents for malignant hilar biliary strictures: a multicenter prospective study.

BACKGROUND: Theoretically, the side-by-side bilateral placement of metal stents may be technically easier than stent-in-stent bilateral placement in stent revision. However, side-by-side placement can be technically challenging, as the deployment of the first stent can preclude the passage of the second stent. AIM: We explored the technical feasibility and revision efficacy of endoscopic bilateral side-by-side stent placement for malignant hilar biliary strictures. METHODS: Forty-four patients with Bismuth type II or higher malignant hilar biliary strictures were enrolled in seven academic tertiary referral centers. Endoscopic placement of side-by-side bilateral metal stents with 7F thin delivery shaft was performed. The outcome measurements were the technical and functional success, adverse events, endoscopic revision success rate, and stent patency. RESULTS: Overall, the technical and functional success rates were 91 % (40/44), and 98 % (39/40), respectively. Two of the failed patients were converted successfully with subsequent contralateral stent-in-stent placement, and the other patients underwent percutaneous intervention. Early stent-related adverse events occurred in 10 %. The endoscopic revision rate due to stent malfunction during follow-up (median: 180 days) was 45 % (18/40; tumor ingrowth in 4 and in-stent sludge impaction/stone formation in 14 patients). The endoscopic revision success rate was 92 % (12/13). Five patients with comorbidity underwent initial percutaneous intervention. The median survival and stent patency periods were 180 and 157 days, respectively. CONCLUSIONS: The sequential placement of a metal stent with a 7F thin delivery shaft in bilateral side-by-side procedures may be feasible and effective for malignant hilar biliary strictures and for endoscopic stent revision.

Feasibility of placing a modified fully covered self-expandable metal stent above the papilla to minimize stent-induced bile duct injury in patients with refractory benign biliary strictures (with videos).

BACKGROUND: Endoscopic placement of fully covered self-expandable metal stents (FCSEMS) has been attempted to manage benign biliary strictures, but currently available FCSEMSs may be associated with unintended complications, including de novo strictures, in patients with normal life expectancy. OBJECTIVE: To evaluate the feasibility of an intraductally placed modified FCSEMS to minimize stent-induced bile duct injury in patients with benign biliary strictures. DESIGN: Prospective observational clinical feasibility study. SETTING: Tertiary-care academic center. PATIENTS: This study involved 21 patients with symptomatic benign biliary strictures in whom conventional endoscopic management failed. INTERVENTION: Strictured segments were 15 mm above the ampulla of Vater. The modified FCSEMS has convex margins, a lasso, and an anti-migrating waist on the central portion. Stents were placed entirely above the papilla and removed after 3 to 5 months. MAIN OUTCOME MEASUREMENTS: Success, complications, removability, midterm outcome. RESULTS: FCSEMSs were successfully placed inside the bile duct in all patients. No episodes of pancreatitis, cholangitis, or sepsis were noted during the stenting period. Stent migration occurred in 4 patients (19.0%), but 3 were asymptomatic during follow-up. All stents were removed successfully with rat-tooth forceps without complications. Post-stenting cholangiograms showed improvement of strictures in 20 of 21 patients, without de novo focal stricture. The clinical success rate was 95.2%, with one recurrent stricture. LIMITATIONS: The small number and lack of comparison with other types of FCSEMSs. CONCLUSION: Temporary intraductal placement of a newly modified FCSEMS effectively improved strictures and prevented potential stent-induced complications in patients with benign biliary strictures. Controlled large-scale trials are needed to confirm the long-term efficacy.

Bioelectric effect utilized a healthcare device for effective management of dental biofilms and gingivitis.

Oral healthcare is a critical condition for high quality of life. According to statistics, gingivitis is one of major diseases in the world (The Global Burden of Disease Study 2019, 3.5 billion population worldwide). Oral diseases, that initiated by a group of multispecies bacteria with diverse extracellular slime that called biofilms, are modifiable risk factors with the cancer, cardiovascular disease, chronic respiratory disease. Hence, effective management of biofilms is important. Since biofilms are comprised of extracellular matrix that inhibit drug diffusion, the traditional antibiotic treatment requires 500 -5000 times more concentration than planktonic bacterial infection. The biofilm cleaning in dentistry includes time-consuming and painful physical brushing. In this work, we have developed a new electric toothbrush in emphasis on demonstration of convenient and painless gingivitis improvement device. For the first time, the toothbrush has been integrated with an electromagnetic technology for effective biofilm removal, known for bioelectric effect (BE). Biofilms consists of electrically charged molecules that are affected by external electric fields. Thus, when an electric field is applied, it creates interruption of metabolism, reduction of enzyme activity, weakening surface attachment, and nonuniform electrolyte distribution, resulting in separation from the surface. Thus, integration of the BE on a toothbrush enables enhanced biofilm reduction. The toothbrush tested with mild gingival patient (N=40) at the department of dentistry, Ulsan University Hospital, South Korea. The patient used the BE toothbrush and non-BE toothbrush consecutively for 2 weeks in each, following their gingival index (GI) and plaque index (PI) measurement for the quantitative analysis. The results demonstrate 1.75 times more decrease of GI in BE toothbrush than the data of the non-BE device (p < 0.05). In conclusion, a new electromagnetic wave toothbrush has been successfully demonstrated especially in reduction of inflammation. Based on this work, we are going to further develop a medical device that dedicated on the treatment of inflammation.

Optimal reproduction of a porcine benign biliary stricture model using endobiliary radiofrequency ablation.

The use of endobiliary radiofrequency ablation (RFA) to generate a benign biliary stricture (BBS) model has a significant reproducibility problem. The aims of this animal study were to create an optimal BBS model using endobiliary RFA and determine the best way to develop it. The first step was performed on the common bile duct (CBD) of 10 miniature pigs using endoscopic RFA with a target temperature-controlled mode (80 â„ƒ, 7 W for 90 s). The second step was performed on the CBD of five miniature pigs to understand more about the time-dependent changes in BBS development and the causes of adverse events. Using the conditions and techniques identified in the previous steps, the third step was conducted to create an optimal BBS model in 12 miniature pigs. In the first trial, four out of 10 animals died (40%) after the procedure due to cholangitis-induced sepsis. Based on this, biliary obstruction was prevented in further steps by placing a biliary plastic stent after RFA application. Histologic examinations over time showed that a severe abscess developed at the RFA application site on the fifth day, followed by fibrosis on the tenth day, and completion on the twentieth day. In the third trial, 11 animals survived (91.7%), the average BBS fibrotic wall thickness was 1107.9 µm (763.1-1864.6 µm), and the degree of upstream biliary dilation was 14.4 mm (11.05-20.7 mm). In conclusion, endobiliary RFA combined with a biliary plastic stent resulted in a safe and reproducible BBS animal model.

Anchoring of a fully covered self-expandable metal stent with a 5F double-pigtail plastic stent to prevent migration in the management of benign biliary strictures.

OBJECTIVES: Fully covered self-expandable metal stents (FCSEMSs) can be effectively placed in patients with benign biliary stricture (BBS). However, stent migration is an inherent problem of FCSEMSs. We evaluated the efficacy of anchoring with a 5F double-pigtail plastic stent (anchoring stent) to prevent migration of an FCSEMS in patients with BBS. METHODS: Between January 2007 and December 2009, 33 of 37 consecutive patients with BBS who had experienced treatment failure of at least one plastic stent placement were prospectively enrolled in this study. The patients with BBS were randomly assigned to undergo FCSEMS placement with or without an anchoring stent (anchoring group: 16 patients; non-anchoring group: 17 patients). The main outcome measures were the stent migration rate and success rates. RESULTS: The technical success rate was 100% in both groups. Significantly less stent migration occurred in the anchoring group (6.3%, 1/16) than in the non-anchoring group (41.2%, 7/17; P=0.024). The median indwelling time was significantly longer in the anchoring group (154 days; range, 86-176 days) than in the non-anchoring group (114 days; range, 19-162 days; P=0.010). Improvement or resolution of the BBS was confirmed in 15 of 16 patients (93.8%) in the anchoring group, and in 12 of 17 patients (70.6%) in the non-anchoring group (P=0.101). CONCLUSIONS: The placement of an anchoring stent appears to be a simple and effective method of preventing premature migration of FCSEMSs in patients with BBS. Appropriately powered studies are needed to confirm this finding.

New Pyrimidinone-Fused 1,4-Naphthoquinone Derivatives Inhibit the Growth of Drug Resistant Oral Bacteria.

BACKGROUND: Dental caries is considered to be a preventable disease, and various antimicrobial agents have been developed for the prevention of dental disease. However, many bacteria show resistance to existing agents. METHODS/PRINCIPAL FINDINGS: In this study, four known 1,4-naphthoquinones and newly synthesized 10 pyrimidinone-fused 1,4-naphthoquinones, i.e. KHQ 701, 702, 711, 712, 713, 714, 715, 716, 717 and 718, were evaluated for antimicrobial activity against Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans, Streptococcus sobrinus, Porphyromonas gingivalis, Actinomyces viscosus and Fusobacterium nucleatum. Pyrimidinone-fused 1,4-naphthoquinones were synthesized in good yields through a series of chemical reactions from a commercially available 1,4-dihydroxynaphthoic acid. MIC values of KHQ 711, 712, 713, 714, 715, 716, 717 and 718 were 6.25-50 µg/mL against E. faecalis (CCARM 5511), 6.25-25 µg/mL against E. faecium (KACC11954) and S. aureus (CCARM 3506), 1.56-25 µg/mL against S. epidermidis (KACC 13234), 3.125-100 µg/mL against S. mutans (KACC16833), 1.56-100 µg/mL against S. sobrinus (KCTC5809) and P. gingivalis (KCTC 5352), 3.125-50 µg/mL against A. viscosus (KCTC 9146) and 3.125-12.5 µg/mL against F. nucleatum (KCTC 2640) with a broth microdilution assay. A disk diffusion assay with KHQ derivatives also exhibited strong susceptibility with inhibition zones of 0.96 to 1.2 cm in size against P. gingivalis. Among the 10 compounds evaluated, KHQ 711, 712, 713, 715, 716 and 717 demonstrated strong antimicrobial activities against the 9 types of pathogenic oral bacteria. A pyrimidin-4-one moiety comprising a phenyl group at the C2 position and a benzyl group at the N3 position appears to be essential for physiological activity. CONCLUSION/SIGNIFICANCE: Pyrimidinone-fused 1,4-naphthoquinones synthesized from simple starting compounds and four known 1,4-naphthoquinones were synthesized and showed strong antibacterial activity to the 9 common oral bacteria. These results suggest that these derivatives should be prospective for the treatment of dental diseases caused by oral bacteria, including drug-resistant strains.