A double-blind comparative study of Chinese herbal medicine Jinlianqingre Effervescent Tablets in combination with conventional therapy for the treatment of uncomplicated hand, foot, and mouth disease.

Chinese herbal medicine Jinlianqingre Effervescent Tablets (JET) are the recommended control measure for uncomplicated hand, foot, and mouth disease (HFMD) by the Ministry of Health of China. However, high-quality evidence to support this recommendation is limited. A total of 288 patients ranging in age from 1 to 13 years were randomly assigned to JET in combination with conventional therapy (mainly including the reduction of temperature by applying physical cooling paste or warm bathing), or conventional therapy with placebo group for 7 days. The objective was to test the hypothesis that JET combination therapy is more effective than conventional therapy for uncomplicated HFMD. A randomized, double-blind, placebo-controlled trial was designed. Our study showed that, compared with conventional therapy, the median time to fever resolution was significantly shorter in the JET combination therapy (8 vs. 80 h; p < 0.0001); the risk of fever resolution increased in the JET combination therapy [hazard ratio, 19.8; 95% confidence interval (CI), 12.8 to 30.7]; the median healing time of rash or oral ulcer was significantly shorter in the JET combination therapy (14 vs. 74 h; p < 0.0001); and the median symptom score for skin or oral mucosa lesions improved more rapidly in the JET combination therapy during the follow-up period. The median duration of hospital stay was 6 days in the JET combination therapy and 7 days in the conventional therapy (p < 0.0001). No significant adverse events and complications were found in both groups. The addition of JET to conventional therapy reduced fever clearance time, healing time of skin or oral mucosa lesions, and duration of hospital stay in children with uncomplicated HFMD.

[Advances in researches on enamel biomimetic mineralization].

Dental enamel biomimetic mineralization is a process to form the enamel-like mineral structures, which possess unique microstructure and exceptional physic-chemical properties, by mimicking the mechanism of natural enamel formation and biomineralization. Varieties of techniques such as molecular mimetic synthesis and molecular self-assembling were used to accomplish the microenvironment and molecular conditions similar to that of natural tooth enamel within human body. Early remineralization and biomineralization is the future of restoration for enamel defect, research on such products have huge potential in clinical applications, with speedy advancement in recent two decades. This review summarizes the major advances in researches on enamel biomimetic mineralization in recent years.

Randomized Clinical Trial on Preventing Root Caries among Community-Dwelling Elders.

Dental root caries is a common disease among elders. More efforts on preventing this disease are needed. Silver diammine fluoride (SDF) is known to prevent dental caries in primary teeth. However, clinical evidence of its efficacy in preventing root surface caries is limited. This clinical trial aimed to compare the effectiveness of SDF in preventing root caries among elders in a water fluoridated area. A total of 323 elders who had at least 5 teeth with exposed root surfaces and who had self-care ability were randomly allocated into 3 intervention groups: group 1 (placebo control), annual application of tonic water; group 2, annual application of SDF solution; group 3, annual application of SDF solution, immediately followed by potassium iodide (KI) solution. Oral hygiene instructions and fluoride toothpaste were provided to all subjects. Status of dental root surface was assessed every 6 mo by the same independent examiner. After 30 mo, 257 (79.6%) elders were reviewed. The mean numbers of root surface with new caries experience in the control, SDF, and SDF/KI groups were 1.1, 0.4, and 0.5, respectively (analysis of variance, P < 0.001). Scheffe's multiple comparison showed that elders who received placebo developed more new root caries lesions ( P < 0.05), while the difference between the SDF and SDF/KI groups was not statistically significant ( P > 0.05). Moreover, elders who had higher visible plaque index scores at 30-mo examination (analysis of covariance, P < 0.001) and those who had higher baseline DMFT scores (analysis of covariance, P = 0.005) developed more new root caries. It is concluded that annual application of SDF or SDF/KI solution is effective in preventing root caries among community-dwelling elders in a fluoridated area ( ClinicalTrials.gov NCT02360124). Knowledge Transfer Statement: Annual topical application of silver diammine fluoride or silver diammine fluoride / potassium iodide solution is effective in preventing dental root surface caries among community-dwelling elders in a fluoridated area.

Randomized clinical trial on arresting dental root caries through silver diammine fluoride applications in community-dwelling elders.

OBJECTIVES: To investigate the effectiveness of silver diammine fluoride (SDF) solution application in arresting dental root caries and to assess the color of arrested caries lesions. METHODS: This study was conducted in elderly centers in Hong Kong. A total of 83 elders with 157 root surfaces with active caries lesion were randomly allocated into 3 groups: Gp1 (placebo control)-annual application of soda water; Gp2-annual application of SDF solution; Gp3-annual application of SDF solution immediately followed by potassium iodide (KI) solution. Color of the arrested root caries lesion was assessed with reference to PANTONE color plates and classified into one of the followings: yellow (7401U); light brown (1245U); dark brown (4635U); and black (Black U). Status of root surfaces was assessed every 6 months by the same independent examiner. RESULTS: After 30 months, 100 (64%) of the included root caries lesions were reviewed. The arrest rates of root caries were 45%, 90%, and 93% in Gp1 (control), Gp2 (SDF) and Gp3 (SDF/KI), respectively (χ(2) test, p<0.001). Pairwise comparisons showed elders in the control group had a lower proportion of the active root caries changed to arrested (p<0.001) and the proportions of root caries being arrested in the SDF and SDF/KI groups were not significantly different (p>0.05). The distributions of arrested caries lesions by color were not significantly different between the SDF and SDF/KI groups (χ(2) test, p>0.05). CONCLUSIONS: Application of SDF solution, with or without application of KI afterwards, is effective in arresting root caries among elders in a water fluoridated area. In the long term, blackening of arrested root caries is not reduced by immediate application of KI after the application of SDF. CLINICAL SIGNIFICANCE: In a water fluoridated area, annual application of SDF solution or SDF/KI solution can arrest dental root caries in elders. In the long term, application of KI does not reduce the blackening of arrested caries lesions caused by SDF.

Conditionally immortalized murine bone marrow stromal cells mediate parathyroid hormone-dependent osteoclastogenesis in vitro.

PTH recruits and activates osteoclasts to cause bone resorption. These actions of PTH are thought to be mediated indirectly via type 1 PTH/PTH-related peptide receptors (PTH1Rs) expressed by adjacent marrow stromal or osteoblastic cells, although some evidence suggests that PTH may act directly on early hematopoietic osteoclast progenitors. We have established clonal, conditionally immortalized, PTH-responsive, bone marrow stromal cell lines from mice that harbor both a transgene encoding a temperature-sensitive mutant of the simian virus 40 large T antigen and deletion of a single allele of the PTH1R gene. Of 60 stromal cell lines isolated, 45 expressed functional PTH1Rs. During coculture with normal murine spleen cells, 5 of 42 such cell lines could support formation of tartrate-resistant acid phosphatase-positive, multinucleated cells (TRAP+ MNCs) in response to 1,25-dihydroxyvitamin D3, but only 2 of these did so in response to PTH. One of these, MS1 cells, expressed numerous cytokines and proteins characteristic of the osteogenic lineage and showed increased production of interleukin-6 in response to PTH. MS1 cells supported dose-dependent induction by rat (r) PTH-(1-34) (0.1-100 nM) of TRAP+ MNCs that expressed calcitonin receptors and formed resorption lacunae on dentine slices. This effect of PTH, which required cell to cell contact between MS1 and spleen cells, was mimicked by coadministration of cAMP analog and phorbol ester but only partially by either agent alone. The carboxyl-terminal fragment rPTH-(53-84) also induced osteoclast-like cell formation, but the maximal effect was only 30% as great as that of rPTH-(1-34). Importantly, rPTH-(1-34) induced TRAP+ MNC formation even when PTH1R-/- osteoclast progenitors (from fetal liver of mice homozygous for ablation of the PTH1R gene) were cocultured with MS1 cells. We conclude that activation of PTH1Rs on cells of the osteoclast lineage is not required for PTH-(1-34)-induced osteoclast formation in the presence of appropriate PTH-responsive marrow stromal cells. MS1 cells provide a useful model for further study of PTH regulation of osteoclastogenesis.

Secondary dentin deposition in dens evaginatus: report of a case.

An unusual case of dens evaginatus in a 22-year-old man is reported. The involved tooth was the right upper second premolar which appeared to have been segregated into coronal and apical segments during the disease process. Although abscess formation was noted in the coronal portion, continuing secondary dentin deposition was found over the displaced apical segment. The pathogenesis of this unusual dentinal bridge formation is proposed based on the microscopic and radiographic findings.

Hyaline ring granuloma: a case report with histochemical and polarized microscopic studies.

An unusual case of hyaline ring granuloma arising from the connective tissue wall of a residual apical periodontal cyst is reported. Hyaline rings with foreign-body type giant cell inclusions were a significant feature in the histopathologic diagnosis. Histochemical and polarized light microscopic studies suggested that the introduction of foreign material, possibly cellulose, through the postextraction socket into the cystic wall may have caused the granulomatous reaction and formation of the hyaline ring granuloma. The clinical features of this case and 66 previously reported cases, as well as the pathogenesis of the hyaline rings, are discussed.

Effects of continuous calcitonin treatment on osteoclasts derived from cocultures of mouse marrow stromal and spleen cells.

BACKGROUND: Continuous calcitonin (CT) treatment for bone diseases associated with increased bone resorption may be followed by prolonged depression of osteoclast response to CT. The mechanisms of this "escape" phenomenon remain unclear. METHODS: We examined the effects of continuous CT treatment on cell formation, calcitonin receptor (CTR) expression, response to CT, and bone resorption of osteoclasts in a coculture of mouse marrow stromal and spleen cells in the presence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Cells were cocultured and treated with salmon CT (sCT) for 7, 14, or 21 days. The effects of continuous CT treatment on osteoclast formation was determined by quantitation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs). CTR expression in osteoclasts was determined by binding of [125I]sCT in autoradiography. Bone resorption and CT responsiveness were assessed by examining the formation of resorption pits and by enumerating osteoclast reattachment on dentine slices after sCT rechallenge. RESULTS: TRAP-positive MNCs appeared in cocultures treated with sCT and were similar in number and morphology to those in control cultures, regardless of the concentration and duration of sCT treatment. A decrease in CTR expression was identified as a loss of silver grains from the TRAP-positive cells in cocultures receiving sCT treatment for 14 or 21 days. Partial recovery of CTR expression in TRAP-positive cells was evident in cocultures treated with sCT for only the first 7 days of coculture. TRAP-positive MNCs in cocultures treated with sCT for 14 or 21 days were resistant to the rechallenge with sCT. They attached to dentine slices and caused numerous resorption pits compared with control cells and cells treated with sCT for the first 7 days of coculture (p < 0.01). CONCLUSION: These findings suggest that the escape phenomenon that develops after continuous CT treatment may be due, at least in part to: 1) loss of responsiveness to CT in existing osteoclasts; and 2) development of new osteoclasts that are CTR-deficient and, therefore, refractory to CT rechallenge.

Effect of silver and fluoride ions on enamel demineralization: a quantitative study using micro-computed tomography.

BACKGROUND: This study aimed to investigate the effect of silver and fluoride ions on demineralization of enamel. METHODS: The coronal parts of 40 extracted sound premolars were prepared into tooth blocks. An unvarnished occlusal surface window (OW) and a flat buccal/lingual surface window (FW) were created for each tooth by covering all other surfaces with an acid-resistant varnish. These blocks were randomly allocated into four groups of 10 blocks each and immersed in respective solutions for 5 minutes: Group 1--2.36 M silver fluoride; Group 2--2.36 M potassium fluoride; Group 3--2.36 M silver nitrate; and Group 4--deionized water. After 7-day immersion in a buffered demineralization solution at pH 4.4, micro-CT scans were taken. RESULTS: Mean lesion depth in the FW area for tooth blocks in AgF, KF, AgNO(3) and control groups were 0 µm, 3.3 ± 10.3 µm, 156.3 ± 30.8 µm, and 173.6 ± 48.6 µm, respectively (p < 0.001). The difference in mean lesion depth between the AgNO(3) and control groups was not statistically significant (p > 0.05). Similar OW and FW lesions were observed in tooth blocks in the AgNO(3) and control groups. CONCLUSIONS: Topical application of a 2.36 M fluoride solution can inhibit demineralization of enamel while topical application of silver ions has little effect.

Randomized trial on fluorides and sealants for fissure caries prevention.

To investigate the effectiveness of topical fluorides in preventing fissure caries, we conducted a randomized controlled trial with parallel groups. In total, 501 children (1,539 molars, 3,078 sites), mean age 9.1 years, who had at least one sound permanent first molar with deep fissures or fissures with signs of early caries were recruited. They were randomly allocated among four groups: (1) resin sealant, single placement; (2) 5% NaF varnish, semi-annual application; (3) 38% silver diamine fluoride (SDF) solution, annual application; and (4) placebo control. Follow-up examinations were conducted every 6 months by a masked examiner. After 24 months, 485 children (97%) were examined. Proportions of pit/fissure sites with dentin caries in the sealant, NaF, SDF, and control groups were 1.6%, 2.4%, 2.2%, and 4.6%, respectively. A multi-level logistic regression analysis accounting for the effects of data clustering and confounding factors showed that fissures in any of the three treatment groups had significantly lower risks of carious cavity development into dentin than did controls (p < 0.05). We concluded that placement of resin sealant, semi-annual application of NaF varnish, and annual application of SDF solution are all effective in preventing pit and fissure caries in permanent molars (ClinicalTrials.gov number CT01446107).

Non-calcifying variant of calcifying epithelial odontogenic tumor with Langerhans cells.

Calcifying epithelial odontogenic tumor (CEOT) is a rare type of odontogenic tumor. The most characteristic feature of the classical CEOT is the presence of amyloid globules and Liesegang ring calcification in the tumor tissue. Here, we present a non-calcifying variant of intraosseous CEOT with the presence of Langerhans cells within tumor epithelial nests in a 52-year-old Taiwanese woman. The patient was referred from a local dentist to our hospital for treatment of a unilocular radiolucent lesion at the right anterior region of the maxilla. The lesion was excised. Microscopically, the tumor was composed of small nests or strands of odontogenic epithelial cells and amorphous eosinophilic globules of amyloid-like materials in a loose fibrous connective tissue stroma. The tumor epithelial cells were positive for pan-cytokeratins (AE1 and AE3). Langerhans cells demonstrated by anti-CD1a staining were found in nests or strands of tumor epithelial cells. The eosinophilic globules were positive for Congo red and showed green birefringence when subjected to polarized light. Review of the English literature revealed two cases of non-calcifying variant of intraosseous CEOT with Langerhans cells in the anterior and premolar regions of the maxilla. Taken together, we suggest that the non-calcifying, Langerhan cell-rich variant of CEOT may have a distinct predilection for occurrence in the anterior and premolar region of the maxilla in contrast to the classical CEOTs that usually occur in the molar and ascending ramus area of the mandible.

Oral post-radiation malignant fibrous histiocytoma: a clinicopathological study.

Five cases of oral malignant fibrous histiocytoma (MFH) in patients who had previously received radiotherapy in the head or neck region were included in this study. There were 3 men and 2 women. Four patients had been irradiated for nasopharyngeal carcinoma (NPC) and the other for a squamous cell carcinoma (SCC) involving the tongue and mouth floor. The MFH developed 2.5-11 years after the initial radiotherapy. Two cases of MFH occurred in the maxilla, two in the mandible, and the remaining one in the tongue, floor of mouth and mandible. Clinically, the oral post-radiation MFH presented as tender, reddish, elastic, lobulated masses with surface ulceration. Radiographic examination of the involved jaws revealed a poorly defined radiolucent lesion without any periosteal or endosteal reaction. The prognosis of these tumors was very poor. Although aggressive multimodality treatment had been applied, 3 of 5 patients eventually died of the disease, with a mean survival time of 17 months after establishing the diagnosis of MFH. In order to ensure the early diagnosis and treatment of this radiation-induced second malignancy, close oral follow-up is mandatory for patients who have received radiotherapy for head and neck malignancies.

High incidence of autoantibodies in Taiwanese patients with oral submucous fibrosis.

BACKGROUND: Previous study has shown a high incidence of autoantibodies including antinuclear (ANA), antismooth muscle (SMA), antigastric parietal cell (GPCA), antithyroid microsomal (TMA), and antireticulin antibodies in a small group of 26 patients with oral submucous fibrosis (OSF). The reasons why some of the OSF patients have high titers of autoantibodies in serum have not been completely explained and no further study on autoantibodies in OSF patients has been done in a large group of patients. METHODS: In this study, we determined the serum levels of ANA, SMA, GPCA, and TMA in a large group of 109 male Taiwanese patients with OSF by an indirect immunofluorescence technique (for ANA, SMA, and GPCA), and by a semiquantitative microtiter particle agglutination test (for TMA). The presence of serum autoantibodies in OSF patients was further correlated with patients' oral habits and the severity of OSF measured by maximum mouth opening (MMO) and sites of involvement. RESULTS: We found that the frequencies of presence of serum ANA (23.9%), SMA (23.9%), and GPCA (14.7%) in OSF patients were significantly higher than those (9.2, 7.3, and 5.5%, respectively) in healthy control subjects (P < 0.01, P < 0.005, and P < 0.05, respectively). Although the frequency of presence of TMA (5.5%) in OSF patients was also greater than that (2.8%) in healthy control subjects, the difference was not significant (P > 0.05). The presence of serum GPCA in OSF patients was significantly associated with daily areca quid (AQ) consumption (P < 0.05). The presence of serum ANA in OSF patients associated with daily AQ consumption was of borderline statistical significance (P = 0.066). However, no significant correlations were demonstrated between the presence of serum autoantibodies in OSF patients and other variables of oral habits, MMO, and sites of involvement. CONCLUSION: In this study, all the 109 OSF patients had AQ chewing habit and 73.4% of the OSF patients swallowed the 'juice' of AQ during the chewing process. The presence of serum GPCA and ANA in OSF patients was associated with daily consumption of AQs. AQ chewing caused mucosal microtrauma, and ulcerations facilitated the diffusion of genotoxic and cytotoxic AQ ingredients into the oral and gastric tissues. Altered autoantigens released from AQ ingredients-damaged cells may induce autoantibody production. Higher frequencies of specific HLA-DR antigens in OSF patients may also help autoantibody production. Therefore, we conclude that the high incidence of autoantibodies in OSF patients may be due to AQ chewing habit, toxic AQ ingredients, and genetic susceptibility of the OSF patients.