A comparative evaluation of the effect of alcoholic and non alcoholic beverages on tooth enamel surface pretreated with ß-tricalcium phosphate, bioactive glass and amine fluoride: an in vitro study.

Background and aims: The aim of this in vitro study is to quantitatively evaluate the effect of different alcoholic and non alcoholic beverages on the tooth enamel surface topography pretreated with various remineralizing agents using Atomic Force Microscopy. Methods: 120 tooth specimens were prepared from 60 freshly extracted intact human premolars by sectioning from mesial to distal surfaces using low speed diamond discs and were randomly assigned to study groups and control group. Specimens of Group I, Group II and Group III were pre-treated with ß-Tri calcium phosphate, bioactive glass and amine fluoride respectively for 4 minutes for 28 days, followed by storage in artificial saliva. All the specimens were evaluated for surface roughness using Atomic Force Microscopy. The specimens were then placed in alcoholic and non-alcoholic beverages for 10 minutes for 4 days and were again analyzed by Atomic Force Microscopy.Descriptive statistics was performed by using the proportional or frequency distribution of the parameters. The respondents were then grouped according to the branch of specialty if any and the data was evaluated by the one-way ANOVA with post-hoc, with p value <0.005. Results: In the present study, among the remineralizing agents tested, bioactive glass was found to be more effective than ß-Tri Calcium Phosphate and Amine Fluoride. Among the demineralizing agents used in this study, the demineralization potential of Coca Cola was found to be highest, followed by wine and green tea pretreated with ß-tricalcium phosphate, bioactive glass and amine fluoride. Conclusions: The present study concluded that all the remineralizing agents tested were found to be effective in inhibiting the demineralization caused by various alcoholic and non alcoholic beverages. Among the remineralizing agents tested, bioactive glass was found to be more effective than ß-tri calcium phosphate and amine fluoride.

In the Quest for Potent and Selective Malic Enzyme 3 Inhibitors for the Treatment of Pancreatic Ductal Adenocarcinoma.

The genome of pancreatic ductal adenocarcinoma (PDAC) is associated with frequent deletion of the tumor suppressor gene SMAD family member 4 (SMAD4) with collateral deletion of its chromosomal neighbor malic enzyme 2 (ME2). In SMAD4 -/- /ME2 -/- PDAC cells, ME3 takes over the function of the ME2 enzyme, and hence therapeutic targeting of ME3 is expected to arrest tumor growth. Hitherto no selective small molecule inhibitor of ME3 has been reported in the context of PDAC. Based on the molecular docking studies and structure-activity relationships with the reported ME1 inhibitor, several analogues of 6-piperazin-1-ylpyridin-3-ol amides have been synthesized and screened for their ME inhibition activity. Among them, compound 16b is identified as the most potent and selective ME3 inhibitor with an IC50 of 0.15 µM on ME3, and with 15- and 9-fold selectivity over ME1 and ME2, respectively. In the cell viability assay, compound 16b exhibited an IC50 of 3.5 µM on ME2-null PDAC cells, viz., BxPC-3.

Comparative Assessment of Enamel Microhardness Using Various Remineralising Agents on Artificially Demineralized Human Enamel.

INTRODUCTION: Various remineralizing agents can be used to remineralize initial carious lesions. AIM: The study aims to compare and evaluate the remineralizing efficiency of Remin Pro (VOCO GmbH, Cuxhaven, Germany), tricalcium phosphate, and HealOzone (CurOzone USA Inc., Ontario, Canada) by measuring the microhardness of enamel. MATERIALS AND METHOD: Forty-five mandibular premolars were collected and divided into three groups (A, B, and C). After sectioning mesiodistally, they were subdivided into the control and test groups. The test group was further subdivided into demineralized (A2a, B2a, and C2a) and remineralized (A2b, B2b, and C2b) groups. All test group samples were demineralized by immersing in demineralizing solutions for 24 hours. Afterwards, A2b, B2b, and C2b samples were remineralized by remineralizing agents (Remin Pro, tricalcium phosphate, and HealOzone) for three minutes (twice a day) for 14 days, and then Vickers microhardness testing (VHN) was performed. RESULT: The microhardness values of the demineralized group were lower compared to the samples of the control groups. In the remineralized group, the mean microhardness values were maximum for HealOzone (293.22 kgmm-2), followed by Remin Pro (287.5660 kgmm-2) and then tricalcium phosphate (282.4660 kgmm-2). CONCLUSION: The application of remineralizing paste proved potent in improving the remineralization in the demineralized enamel surface.

Evaluation of Pre- and Post-loading Peri-implant Crestal Bone Levels Using Cone-beam Computed Tomography: An In Vivo Study.

AIM: To evaluate the buccal, lingual, mesial, and distal crestal bone around implant using CBCT analysis having buccal crestal bone width of 1 mm after placement of implant and after 3 months of loading. MATERIALS AND METHODS: Twenty-five patients between 18 and 60 years of age with adequate bone width and height were selected for this in-vivo study with single or multiple missing teeth. Surgical stent was fabricated for all of them by using self-cure acrylic resin for selection of implant according to the availability of bone, and gutta-percha was used as radio-opaque marker to locate the implant site. After proper analysis, in the first stage surgery, implants were placed. After 3 months to this, the second stage surgery was performed followed by elastomeric impression for porcelain fused to metal prosthesis fabrication. The buccal, lingual, mesial, and distal bone width and height were evaluated by using cone-beam computed tomography (CBCT). CBCT was standardized in terms of FOV (field of vision), slice thickness, and interval. After 3 months of loading, CBCT was taken to evaluate the alteration in the crestal bone around implants. Pre- and post-loading, crestal bone on four locations was measured by using CBCT software. RESULTS: There is significant bone loss at all the locations, buccal, lingual, mesial, and distal, at the time of placement and after 3 months of loading of implant (p <0.05). The mean difference of 0.840, 0.933, 0.840, and 0.380 at buccal, lingual, mesial, and distal locations, respectively, shows statistically significant difference in pre- and post-values of mean bone loss at buccal, lingual, mesial, and distal positions. Pre-loading bone loss was maximum in the distal surface, while post-loading bone loss was maximum in the buccal surface. CONCLUSION: From this study, it is concluded that although crestal bone loss was higher before implant placement, there was significant alteration in crestal bone even after loading of implant. CLINICAL SIGNIFICANCE: It is widely accepted that the bone loss around the implant crest module is multidisciplinary in nature. Long-term preservation of the crestal bone is a paramount for successfully functioning of dental implants. Preserving crestal bone will help in dissipating the functional load. With proper treatment planning by the practitioner, this technical contribution to the crestal bone loss can be minimized and long-term survival of dental implants can be achieved.

Evaluation of Fracture Resistance of Reattached Fractured Tooth Fragment Stored in Different Storage Media: An In Vitro Study.

AIM: To evaluate the fracture resistance of coronal fractured tooth fragments stored in five different storage media when reattached with nanohybrid flowable composite. MATERIALS AND METHODS: The crown portion of 50 extracted human permanent maxillary central incisors were divided into three equal parts (incisal third, middle third and cervical third) and then marked incisal third were cut with the diamond disk. These were divided into five equal groups according to the type of storage media used i.e. dry storage, fresh tender coconut water, HBSS, milk, and propolis for 2 hours. Coronal fractured part with their respective apical parts were then reattached with flowable composite (G-aenial Universal Flo, GC India), then after thermocycling process samples were subjected to universal testing machine for testing fracture resistance. The collected data were subjected to statistical analysis using one way ANOVA and Post-hoc Tukey test. RESULTS: The obtained results revealed that large amount of force is required to fracture the reattached teeth which were stored in milk and fresh tender coconut water as compared to those which were stored in dry environment, HBSS and propolis. CONCLUSION: In this study, maximum fracture resistance was seen in teeth stored in milk and fresh tender coconut water. Therefore, these two were considered as better storage media. CLINICAL SIGNIFICANCE: Due to increased interest towards the use of tooth colored restoration, recently, fractured teeth reattachment treatment procedure gaining attention by preserving life like translucency of treated tooth.

Evaluation of Sealing Ability of Three Root Canal Sealers: An In Vitro Study.

AIM: To evaluate the sealing ability of three different types of sealers using confocal laser microscopy. MATERIALS AND METHODS: Sixty extracted single-root premolars were selected and divided into three groups (20 teeth in each group) according to the type of sealer used, namely, mineral trioxide aggregate (MTA) Fillapex, AH Plus, and Bio C Sealer. Root canal preparation and obturation were done in all the samples. Roots was dissected transversely in apical plane. Percentage of gap from region to canal circumference was calculated using a confocal laser microscope. Samples were subjected to statistical analysis. RESULTS: High dye penetration was seen with AH Plus compared to MTA Fillapex and least with Bio C Sealer. The AH Plus is the best sealer with respect to seal ability of all the three. CONCLUSION: This study helps to appraise the sealing ability of the different types of sealers using confocal laser microscopy which is useful for the success of root canal treatment. CLINICAL SIGNIFICANCE: As sealer has to seal voids, foramina, and canals, it should have good penetration for the success of root canal treatment.

Evaluation of Eruption Pattern and Caries Occurrence among Children Affected with Fluorosis.

AIM: The aim of this study was to evaluate eruption pattern and occurrence of caries in children affected with fluorosis. MATERIALS AND METHODS: One hundred and fifty subjects (75 each with/without fluorosis) with age group of 7-8 years were selected. Dental fluorosis assessed on the buccal surfaces of the permanent incisors and molars and scored using the Thylstrup and Fejerskov index. The tooth were scored as emerged when at least one cusp of the tooth was visible in the mouth. Caries attack rate in primary and permanent teeth were estimated using DMFS and defs index in fluorosis patient. The findings were subjected to statistical analysis. The data were analyzed using Student "t" test and ANOVA "F" test. RESULTS: There was statistically highly significant difference found in the incidence of occlusal, mesioproximal, and distoproximal caries between fluorotic and nonfluorotic patients (p < 0.001). The result of present study showed a nonsignificant association between fluoride exposure parameter and median emergence ages of permanent incisors and molar teeth. On the other hand, caries occurrence shows a significant association with fluorosis. CONCLUSION: In this study, a significant positive correlation exists in the prevalence of caries and fluorosis. It is concluded that occlusal and proximal caries are less pronounced in fluorosis patients. CLINICAL SIGNIFICANCE: Dental caries is a public health problem. In this study, we study the fluoride effect since the predominant cariostatic effect of fluoride is beneficial in extensive caries reduction without a concomitant risk of dental fluorosis. How to cite this article: Trivedi S, Trivedi A, Banda NR, et al. Evaluation of Eruption Pattern and Caries Occurrence among Children Affected with Fluorosis. J Contemp Dent Pract 2019;20(10):1217-1222.

Amelanotic malignant melanoma of the cervical oesophagus.

We report the case of a young woman who presented with progressive dysphagia and swelling in the anterior aspect of the neck of short duration. On evaluation, she was diagnosed with amelanotic malignant melanoma of the cervical oesophagus. She underwent total laryngopharyngo-oesophagectomy with gastric transposition with bilateral modified radical neck dissection with feeding jejunostomy and a permanent tracheostomy with postoperative combined chemoradiation therapy. However, in spite of aggressive treatment, the patient expired 8 months after initial presentation with distant metastasis.

Glucagon-like peptide-2 increases dysplasia in rodent models of colon cancer.

The intestinal hormone, glucagon-like peptide-2 (GLP-2), enhances intestinal growth and reduces inflammation in rodent models. Hence, a degradation-resistant GLP-2 analog is under investigation for treatment of Crohn's disease. However, GLP-2 increases colonic dysplasia in murine azoxymethane (AOM)-induced colon cancer. Considering the increased colon cancer risk associated with chronic colitis, we have therefore examined the effects of long-acting hGly(2)GLP-2, as well as of endogenous GLP-2 using the antagonist hGLP-2(3-33) in two novel models of inflammation-associated colon cancer: rats fed the carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and a high-fat diet (HFD) for one or three cycles, and mice with chronic dextran sodium-sulfate (DSS)-induced colitis administered AOM. hGly(2)GLP-2 treatment of one-cycle PhIP/HFD rats increased the number of colonic aberrant crypt foci by 72 ± 11% (P < 0.01). Fifty-one weeks after three PhIP/HFD cycles, hGly(2)GLP-2-treated rats had a 22% incidence of colon cancer, compared with 0% in vehicle-treated rats. AOM-DSS mice treated with vehicle or hGly(2)GLP-2 had high-grade dysplasia/colon cancer incidences of 56 and 64%, respectively, compared with 46% in hGLP-2(3-33)-treated AOM-DSS animals (P < 0.05). Unexpectedly, hGLP-2(3-33) also reduced the colitis damage score by 32.0 ± 8.4% (P < 0.05). All high-grade dysplastic/cancerous tumors had nuclear localization of ß-catenin although ß-catenin mRNA transcript and protein levels did not differ between treatment groups. GLP-2 receptor mRNA expression also was not different. However, hGLP-2(3-33)-treated mice had markedly reduced numbers of doublecortin-and-calmodulin-kinase-like-1-positive stem cells, by 73.7 ± 8.6% (P < 0.05). In conclusion, the results of this study indicate a role for hGly(2)GLP-2 and endogenous GLP-2 as potential cancer promoters in rodents.

Novel biological action of the dipeptidylpeptidase-IV inhibitor, sitagliptin, as a glucagon-like peptide-1 secretagogue.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted into the circulation by the intestinal L cell. The dipeptidylpeptidase-IV (DPP-IV) inhibitor, sitagliptin, prevents GLP-1 degradation and is used in the clinic to treat patients with type 2 diabetes mellitus, leading to improved glycated hemoglobin levels. When the effect of sitagliptin on GLP-1 levels was examined in neonatal streptozotocin rats, a model of type 2 diabetes mellitus, a 4.9 ± 0.9-fold increase in basal and 3.6 ± 0.4-fold increase in oral glucose-stimulated plasma levels of active GLP-1 was observed (P < 0.001), in association with a 1.5 ± 0.1-fold increase in the total number of intestinal L cells (P < 0.01). The direct effects of sitagliptin on GLP-1 secretion and L cell signaling were therefore examined in murine GLUTag (mGLUTag) and human hNCI-H716 intestinal L cells in vitro. Sitagliptin (0.1-2 µM) increased total GLP-1 secretion by mGLUTag and hNCI-H716 cells (P < 0.01-0.001). However, MK0626 (1-50 µM), a structurally unrelated inhibitor of DPP-IV, did not affect GLP-1 secretion in either model. Treatment of mGLUTag cells with the GLP-1 receptor agonist, exendin-4, did not modulate GLP-1 release, indicating the absence of feedback effects of GLP-1 on the L cell. Sitagliptin increased cAMP levels (P < 0.01) and ERK1/2 phosphorylation (P < 0.05) in both mGLUTag and hNCI-H716 cells but did not alter either intracellular calcium or phospho-Akt levels. Pretreatment of mGLUTag cells with protein kinase A (H89 and protein kinase inhibitor) or MAPK kinase-ERK1/2 (PD98059 and U0126) inhibitors prevented sitagliptin-induced GLP-1 secretion (P < 0.05-0.01). These studies demonstrate, for the first time, that sitagliptin exerts direct, DPP-IV-independent effects on intestinal L cells, activating cAMP and ERK1/2 signaling and stimulating total GLP-1 secretion.

Loss of glucagon-like peptide-2-induced proliferation following intestinal epithelial insulin-like growth factor-1-receptor deletion.

BACKGROUND & AIMS: Glucagon-like peptide-2 (GLP-2) is an intestinal hormone that promotes growth of the gastrointestinal tract. Although insulin-like growth factor (IGF)-1 and the IGF-1 receptor (IGF-1R) are required for GLP-2-induced proliferation of crypt cells, little is known about localization of the IGF-1R which mediates the intestinotropic actions of GLP-2. METHODS: We examined intestinal growth and proliferative responses in mice with conditional deletion of IGF-1R from intestinal epithelial cells (IE-igf1rKO) after acute administration (30-90 min) of GLP-2, in response to 24-hour fasting and re-feeding (to induce GLP-2-dependent adaptation), and after chronic exposure (10 days) to GLP-2. RESULTS: IE-igf1rKO mice had normal small intestinal weight, morphometric parameters, proliferative indices, and distribution of differentiated epithelial cell lineages. Acute administration of GLP-2 increased nuclear translocation of ß-catenin in non-Paneth crypt cells and stimulated the crypt-cell proliferative marker c-Myc in control but not IE-igf1rKO mice. Small intestinal weight, crypt depth, villus height, and crypt-cell proliferation were decreased in control and IE-igf1rKO mice after 24-hour fasting. Although re-feeding control mice restored all of these parameters, re-fed IE-igf1rKO mice had reductions in adaptive regrowth of the villi and crypt-cell proliferation. Control mice that were given chronic GLP-2 had increases in small intestinal weight, mucosal cross-sectional area, crypt depth, villus height, and crypt-cell proliferation. However, the GLP-2-induced increase in crypt-cell proliferation was not observed in IE-igf1rKO mice, and growth of the crypt-villus axis was reduced. CONCLUSIONS: The proliferative responses of the intestinal epithelium to exogenous GLP-2 administration and conditions of GLP-2-dependent adaptive re-growth require the intestinal epithelial IGF-1R.

Carcinogenic effects of exogenous and endogenous glucagon-like peptide-2 in azoxymethane-treated mice.

Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent intestinotropic hormone that promotes intestinal growth, via increased intestinal proliferation and decreased apoptosis, as well as increases in nutrient absorption and barrier function. The long-acting analog h(Gly(2))GLP-2[1-33] is currently being tested for treatment of short bowel syndrome and Crohn's disease. However, the role of GLP-2 in colon carcinogenesis is controversial. To assess the intestinotropic effects of exogenous and endogenous GLP-2, C57BL6/J mice were injected with 1 microg h(Gly(2))GLP-2[1-33]; 30 or 60 ng hGLP-2[3-33], a GLP-2 receptor antagonist; or PBS (4 wk, twice a day, sc). Chronic h(Gly(2))GLP-2[1-33] increased small intestinal weight/body weight (P < 0.001), villus height (P < 0.001), crypt depth (P < 0.001), and crypt cell proliferation, as measured by expression of the proliferative marker Ki67 (P < 0.05-0.01). In contrast, chronic hGLP-2[3-33] decreased small intestinal weight/body weight (P < 0.05) and colon weight/body weight (P < 0.05). To assess the carcinogenic effects of endogenous and exogenous GLP-2, separate mice were injected with azoxymethane (10 mg/kg, 4 wk, every 7 d, ip), followed by 1.5 microg h(Gly(2))GLP-2[1-33], 30 ng hGLP-2[3-33], or PBS (4 wk, twice a day, sc) 2 or 12 wk thereafter. At 10 or 46 wk after azoxymethane treatment, the numbers of aberrant crypt foci increased with h(Gly(2))GLP-2[1-33] (P < 0.001) and decreased with hGLP-2[3-33] (P < 0.01-0.05) treatment. Furthermore, mucin-depleted aberrant foci, consistent with progressive dysplasia, were almost exclusively present in h(Gly(2))GLP-2[1-33]-treated mice (P < 0.01-0.001). Additionally, adenocarcinomas developed in h(Gly(2))GLP-2[1-33]-treated mice but not in those receiving hGLP-2[3-33] or PBS. Taken together, these studies indicate that chronic treatment with GLP-2 enhances colon carcinogenesis, whereas antagonism of the GLP-2 receptor decreases dysplasia, with possible implications for human therapy.